
A Paradigm Shift in the Management of Patients with Parkinson's Disease.
Neuro-degenerative diseases
BACKGROUND:Technological evolution leads to the constant enhancement of monitoring systems and recording symptoms of diverse disorders. SUMMARY:For Parkinson's disease, wearable devices empowered with machine learning analysis are the main modules for objective measurements. Software and hardware improvements have led to the development of reliable systems that can detect symptoms accurately and be implicated in the follow-up and treatment decisions. KEY MESSAGES:Among many different devices developed so far, the most promising ones are those that can record symptoms from all extremities and the trunk, in the home environment during the activities of daily living, assess gait impairment accurately, and be suitable for a long-term follow-up of the patients. Such wearable systems pave the way for a paradigm shift in the management of patients with Parkinson's disease.
10.1159/000533798
Prevalence and incidence of Parkinson's disease in Europe.
von Campenhausen Sonja,Bornschein Bernhard,Wick Regina,Bötzel Kai,Sampaio Cristina,Poewe Werner,Oertel Wolfgang,Siebert Uwe,Berger Karin,Dodel Richard
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
OBJECTIVE:To provide an overview on the prevalence and incidence of Parkinson's disease (PD) in selected European countries. BACKGROUND:PD is a common disease of unknown etiology. Accurate information on the epidemiology of PD is critical to inform health policy. An aging population will lead to more patients with PD; thus, the high financial burden PD places on society will increase. MATERIAL AND METHODS:A systematic literature search was performed to identify studies on the prevalence and incidence of PD in the following European countries: Austria, the Czech Republic, France, Germany, Italy, The Netherlands, Portugal, Spain, Sweden and United Kingdom. Only published studies were included. Abstracts, reviews, meta-analyses and letters to the editor were excluded. There were no language restrictions. Data were extracted using a standardized assessment form, and evidence tables were used to systematically report and compare the data. RESULTS:Of 39 identified studies, most (87%) reported estimates of PD prevalence rates, while only a few (13%) reported estimates of PD annual incidence rates. Crude prevalence rate estimates ranged from 65.6 per 100,000 to 12,500 per 100,000 and annual incidence estimates ranged from 5 per 100,000 to 346 per 100,000. No publications could be identified for Austria or the Czech Republic. DISCUSSION AND CONCLUSION:The observed variations in prevalence and incidence rates may result from environmental or genetic factors, but might also be a consequence of differences in methodologies for case ascertainment, diagnostic criteria, or age distributions of the study populations. The comparability of existing studies is limited.
10.1016/j.euroneuro.2005.04.007
Young-onset Parkinson's disease: a clinical review.
Golbe L I
Neurology
Young-onset Parkinson's disease (YOPD) is arbitrarily defined as that which produces initial symptoms between the ages of 21 and 39, inclusive. The special problems and concerns of the patient with YOPD present as much of a challenge and opportunity for the clinician as the disease itself does for the researcher. In contrast to juvenile parkinsonism, which is a heterogeneous group of clinicopathologic entities presenting (also arbitrarily) before age 21, YOPD appears to be the same nosologic entity as older-onset PD. It comprises approximately 5% of referral populations in Western countries and about 10% in Japan. Its annual incidence relative to the population at risk is about 1/10 that of PD at age sixty. YOPD tends to have more gradual progression of parkinsonian signs and symptoms, earlier appearance of levodopa-related dyskinesias and levodopa-dose-related motor fluctuations, and frequent presence of dystonia as an early or presenting sign. Studies conflict with regard to the suspected greater familial frequency and lesser frequency of dementia than in older-onset PD.
10.1212/wnl.41.2_part_1.168
SPECT molecular imaging in Parkinson's disease.
Wang Ling,Zhang Qi,Li Huanbin,Zhang Hong
Journal of biomedicine & biotechnology
Parkinson's disease (PD) is a common disorder, and the diagnosis of Parkinson's disease is clinical and relies on the presence of characteristic motor symptoms. The accuracy of the clinical diagnosis of PD is still limited. Functional neuroimaging using SPECT technique is helpful in patients with first signs of parkinsonism. The changes detected may reflect the disease process itself and/or compensatory responses to the disease, or they may arise in association with disease- and/or treatment-related complications. This paper addresses the value of SPECT in early differential diagnosis of PD and its potential as a sensitive tool to assess the pathophysiology and progression, as well as the therapeutic efficacy of PD.
10.1155/2012/412486
Biomarkers in Parkinson's disease.
Dorsey E Ray,Holloway Robert G,Ravina Bernard M
Expert review of neurotherapeutics
Parkinson's disease (PD) is a common neurodegenerative disorder that is largely diagnosed and managed clinically. Biomarkers, as indicators of underlying biological processes, offer the potential to identify individuals at risk for PD, screen new therapies, assist in the diagnosis and help optimize management of PD. However, to date, biomarkers, despite their considerable promise, have had limited utility in clinical trials and practice.
10.1586/14737175.6.6.823
New Symptomatic Treatments for the Management of Motor and Nonmotor Symptoms of Parkinson's Disease.
Taddei Raquel N,Spinnato Federica,Jenner Peter
International review of neurobiology
Motor symptoms are core features of Parkinson's disease, while nonmotor symptoms are present from the prodromal stage. Management strategies for the motor symptoms of Parkinson's disease have been widely researched and there have been many advances. Therapy has evolved from oral therapy to once a day to nonoral strategies, both for rescue and for infusion therapy. Treatment for nonmotor symptoms, however, has remained a key unmet need, although of late evidence base for management of some nonmotor symptoms such as pain, dementia, aspects of sleep dysfunction, and constipation has emerged. However, management of many nonmotor symptoms such as anxiety, apathy, fatigue, and insomnia remains uncharted. In this review, we address these management strategies and discuss the evidence base of available therapies.
10.1016/bs.irn.2017.03.004
REM sleep behavior disorder portends poor prognosis in Parkinson's disease: A systematic review.
Kim Yoon,Kim Young Eun,Park Eun Ok,Shin Chae Won,Kim Han-Joon,Jeon Beomseok
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
REM sleep behavior disorder (RBD) is a parasomnia wherein a loss of REM sleep atonia manifests as dream-enactment, often violent. Aside from its significance as a predictor of PD, RBD in PD may imply more than merely screaming at night and experiencing sleep fragmentation. To probe its significance as a prognostic factor in PD, we performed a systematic literature review. Analysis of prospective studies reveals baseline RBD confers a higher risk of developing dementia and hallucinations. In cross-sectional studies, RBD is associated with the non-tremor predominant motor phenotype and autonomic dysfunction. Clinical, imaging, and autopsy studies support the presence of dense and diffuse pathology extending beyond the brainstem in PD with RBD. As RBD in PD is associated with a greater disease burden and an increased risk of mortality, we propose the RBD subtype in PD to highlight that RBD may mark a distinct subtype with relatively poor prognosis.
10.1016/j.jocn.2017.09.019
Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment.
Pagonabarraga Javier,Kulisevsky Jaime,Strafella Antonio P,Krack Paul
The Lancet. Neurology
Normal maintenance of human motivation depends on the integrity of subcortical structures that link the prefrontal cortex with the limbic system. Structural and functional disruption of different networks within these circuits alters the maintenance of spontaneous mental activity and the capacity of affected individuals to associate emotions with complex stimuli. The clinical manifestations of these changes include a continuum of abnormalities in goal-oriented behaviours known as apathy. Apathy is highly prevalent in Parkinson's disease (and across many neurodegenerative disorders) and can severely affect the quality of life of both patients and caregivers. Differentiation of apathy from depression, and discrimination of its cognitive, emotional, and auto-activation components could guide an individualised approach to the treatment of symptoms. The opportunity to manipulate dopaminergic treatment in Parkinson's disease allows researchers to study a continuous range of motivational states, from apathy to impulse control disorders. Parkinson's disease can thus be viewed as a model that provides insight into the neural substrates of apathy.
10.1016/S1474-4422(15)00019-8
Phenomenology and epidemiology of impulsive-compulsive behaviours in Parkinson's disease, atypical Parkinsonian disorders and non-Parkinsonian populations.
Maloney Eimer M,Djamshidian Atbin,O'Sullivan Sean S
Journal of the neurological sciences
Impulsive-compulsive behaviours are common, quality of life affecting consequences of dopamine replacement therapy which are well recognized in patients with idiopathic Parkinson's disease. Details of the occurrence and nature of these disorders in the atypical parkinsonian neurodegenerative disorders, and in non-Parkinson's patients prescribed dopaminergic stimulation for other disease processes, are slowly emerging. Here we review what is known about the phenomenology, epidemiology and risk factors for impulsive-compulsive behaviours in Parkinson's disease and in other, less well studied, patient groups. By analyzing the available published data, this review identifies potential clues as to the underlying neurobiological mechanism of these disorders, and further identifies critical gaps yet to be addressed.
10.1016/j.jns.2016.12.058
Emerging preclinical interest concerning the role of circadian function in Parkinson's disease.
Willis Gregory L,Freelance Christopher B
Brain research
The importance of circadian function in the aetiology, progression and treatment of Parkinson's disease is a topic of increasing interest to the scientific and clinical community. While clinical studies on this theme are relatively new and limited in number there are many preclinical studies which explore possible circadian involvement in Parkinson's disease and speculate as to the mechanism by which clinical benefit can be derived by manipulating the circadian system. The present review explores the sequelae of circadian related studies from a historical perspective and reveals mechanisms that may be involved in the aetiology and progression of the disease. A systematic review of these studies also sets the stage for understanding the basic neuroscientific approaches which have been applied and provides new direction from which circadian function can be explored.
10.1016/j.brainres.2017.09.027
Parkinson's disease--the shaking palsy. Underlying factors, diagnostic considerations, and clinical course.
Conley S C,Kirchner J T
Postgraduate medicine
Parkinson's disease is a progressive neurologic disorder without cure. About 1% of the US population over 50 years of age is afflicted. Loss of dopaminergic neurons originating in the substantia nigra is the typical pathologic feature. It is theorized that both genetic and environmental factors have a role in the etiology of the disease. The classic tetrad of parkinsonian signs includes tremor, rigidity, bradykinesia, and disturbances in posture and gait. Initial signs and symptoms can be subtle and nonspecific. As the disease progresses, vocal, neurologic, autonomic, and psychiatric complications may develop. Mortality rates have not changed in 30 years despite new therapy. Differentiating true Parkinson's disease from other causes of parkinsonism can be challenging but is crucial to outcome.
10.3810/pgm.1999.07.604
Personality traits in patients with Parkinson's disease: assessment and clinical implications.
Poletti Michele,Bonuccelli Ubaldo
Journal of neurology
This study reviews empirical evidence on the association between personality traits and Parkinson's disease (PD), with a twofold aim. First, to better identify non-motor symptoms, such as affective symptoms and personality changes, that could help to define the pre-motor phase of PD; second, to better understand the neurobiological bases of personality traits, a goal that is not fully accomplished by a purely anatomical approach. A literature review was performed on studies of personality traits in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in July 2011. We found evidence that the existence of a characteristic premorbid personality profile of PD patients is not actually sustained by robust empirical evidence, mainly due to the methodological bias of the retrospective assessment of personality; PD patients present a personality profile of low novelty seeking and high harm avoidance. We concluded that the definition of a pre-motor phase of PD, based on non-motor symptoms, should search for the presence of concomitant affective disorders and for a positive psychiatric history for affective disorders rather than for a typical personality profile or personality changes. The low novelty seeking profile is probably related to the dopaminergic deficit, while the high harm avoidance profile is probably associated with the presence of affective disorders. Clinical implications of these findings, in regard to personality assessment and pharmacological treatments in PD, are also discussed.
10.1007/s00415-011-6302-8
[Impulsive-compulsive disorders in Parkinson's Disease: influence on individual and social decision-making processes].
Ponsi Giorgia,Panasiti Maria Serena
Rivista di psichiatria
AIM:Parkinson's Disease (PD) has been considered for a long time as a neurodegenerative disorder affecting mainly motor functions, because of the involvement of basal ganglia. Recent research has shown that these brain structures have a crucial role even in higher level cognitive and social functions, as executive ones, impulse control and decision-making. METHOD:A research of the peer-reviewed scientific literature was conducted in order to identify articles on the dysfunctions in individual and social decision-making in PD. RESULTS AND DISCUSSION:This work provides the reader with a literature review on individual and social decision-making processes in PD, highlighting how the existence of impulse control disorders and the associated reward-seeking behaviors might elucidate the social symptoms of PD, both in terms of abnormal risk proneness and/or reward salience.
10.1708/3417.33997
Fear-of-falling activity-avoidance behavior in people with Parkinson's disease: a scoping review protocol.
JBI evidence synthesis
OBJECTIVE:The objective of this review is to explore existing literature related to fear of falling activity avoidance behavior and identify what is known about this phenomenon in people with Parkinson's disease. INTRODUCTION:Falling and fear of falling are significant concerns for persons with Parkinson's disease. Fear of falling is a significant problem over and above falling itself and can lead to activity avoidance. Activity-avoidance behavior is a risk factor for increased falls and can lead to further functional decline. A better understanding of the fear of falling and the associated avoidance behavior can inform screening, evaluation, and interventions to decrease fall risk and improve activity engagement and quality of life for persons with Parkinson's disease. INCLUSION CRITERIA:This review will consider studies published in English that include individuals diagnosed with Parkinson's disease experiencing fear of falling that impacts activity engagement with no limit on participant age or time of publication. METHODS:JBI methodology will be used to conduct this scoping review. A three-step search strategy will be utilized. The databases to be searched include MEDLINE (PubMed), Embase (Elsevier), Scopus (Elsevier), APA PsycINFO (EBSCO), CINAHL (EBSCO), Papers First (OCLC), and ProQuest Dissertations and Theses (ProQuest). Two independent reviewers will screen the titles, abstracts, and full text of the selected studies. Data collection will be performed with a tool developed by the researchers based on the standardized tool from JBI SUMARI. Data will be presented in a comprehensive narrative summary.
10.11124/JBIES-20-00396
Gut microbiota, 1013 new pieces in the Parkinson's disease puzzle.
Scheperjans Filip
Current opinion in neurology
PURPOSE OF REVIEW:Gastrointestinal dysfunction is highly prevalent in Parkinson's disease and may precede motor symptoms by more than a decade. It has been proposed that the neurodegenerative cascade may actually be initiated in the gut with subsequent spreading to the brain and that gut microbiota could be involved in this process. This review provides a short introduction into the methodology of microbiome-wide association studies and discusses the recently published first comprehensive assessments of gut microbiota in Parkinson's disease. RECENT FINDINGS:Three case-control studies have studied gut microbiota composition in Parkinson's disease and all found significant differences between Parkinson's disease patients and controls. However, most of the differentially abundant taxa as well as associations of microbiota with clinical variables differed between studies. This may at least in part be explained by methodological differences between studies in terms of selection of participants, analysis pipelines, statistical analysis, and confounder control. SUMMARY:Current evidence suggests that there are alterations of gut microbiota in Parkinson's disease, but the exact nature of these changes is not established. Future larger studies should assess gut microbiota in Parkinson's disease covering diverse geographical regions, ethnicities, disease stages, and phenotypes using well-defined selection criteria for patients and controls and standardized methodology.
10.1097/WCO.0000000000000389
[Advanced Parkinson's disease].
Ziégler Marc
Psychologie & neuropsychiatrie du vieillissement
The stage of advanced Parkinson's disease usually occurs 10 years after the diagnosis but sometimes after 30 years. It is characterized by a severe handicap with gait disorders, posture changes, speech abnormalities and deglutition perturbations. Cognitive disorders (hallucinations, delirium, delusions, dementia) did not occur in all patients. Dysautonomic disorders are usual. Treatment is difficult and may include paradoxical prescriptions such as both apomorphine pump and clozapine.
A Comprehensive Study of miRNAs in Parkinson's Disease: Diagnostics and Therapeutic Approaches.
CNS & neurological disorders drug targets
Parkinson's disease (PD) is the second most debilitating neurodegenerative movement disorder. It is characterized by the presence of fibrillar alpha-synuclein amassed in the neurons, known as Lewy bodies. Certain cellular and molecular events are involved, leading to the degeneration of dopaminergic neurons. However, the origin and implication of such events are still uncertain. Nevertheless, the role of microRNAs (miRNAs) as important biomarkers and therapeutic molecules is unquestionable. The most challenging task by far in PD treatment has been its late diagnosis followed by therapeutics. miRNAs are an emerging hope to meet the need of early diagnosis, thereby promising an improved movement symptom and prolonged life of the patients. The continuous efforts in discovering the role of miRNAs could be made possible by the utilisation of various animal models of PD. These models help us understand insights into the mechanism of the disease. Moreover, miRNAs have been surfaced as therapeutically important molecules with distinct delivery systems enhancing their success rate. This review aims at providing an outline of different miRNAs implicated in either PD-associated gene regulation or involved in therapeutics.
10.2174/1871527321666220111152756
Brain microstructural alterations of depression in Parkinson's disease: A systematic review of diffusion tensor imaging studies.
Human brain mapping
Depression, a leading cause of disability worldwide, is also the most prevalent psychiatric problem among Parkinson disease patients. Both depression and Parkinson disease are associated with microstructural anomalies in the brain. Diffusion tensor imaging techniques have been developed to characterize the abnormalities in cerebral tissue. We included 11 studies investigating brain microstructural abnormalities in depressed Parkinson's disease patients. The included studies found alterations to essential brain structural networks, including impaired network integrity for specific cortical regions, such as the temporal and frontal cortices. Additionally, findings indicate that microstructural changes in specific limbic structures, such as the prefronto-temporal regions and connecting white matter pathways, are altered in depressed Parkinson's disease compared to non-depressed Parkinson's disease and healthy controls. There remain inconsistencies between studies reporting DTI measures and depression severity in Parkinson disease participants. Additional research evaluating underlying neurobiological relationships between major depression, depressed Parkinson's disease, and non-depressed Parkinson's disease is required to disentangle further mechanisms that underlie depression and related somatic symptoms, in Parkinson disease.
10.1002/hbm.26015
[Geriatric particularities of Parkinson's disease: Clinical and therapeutic aspects].
Belin J,Houéto J L,Constans T,Hommet C,de Toffol B,Mondon K
Revue neurologique
Parkinson's disease (PD) is a frequent and complex progressive neurological disorder that increases in incidence with age. Although historically PD has been characterized by the presence of progressive dopaminergic neuronal loss of the substantia nigra, the disease process also involves neurotransmitters other that dopamine and regions of the nervous system outside the basal ganglia. Its clinical presentation in elderly subjects differs from that in younger subjects, with more rapid progression, less frequent tremor, more pronounced axial signs, more frequent non-motor signs linked to concomitant degeneration of non-dopaminergic systems, and more frequent associated lesions. Despite the high prevalence of PD in elderly subjects, few therapeutic trials have been conducted in geriatric patients. Nevertheless, to improve functional disability while ensuring drug tolerance, the principles of optimized and multidisciplinary clinical management have to be known. The aim of this review is to provide an update on clinical and therapeutic features of PD specifically observed in elderly subjects.
10.1016/j.neurol.2015.08.002
Role of the VPS35 D620N mutation in Parkinson's disease.
Mohan Megha,Mellick George D
Parkinsonism & related disorders
Parkinson's disease (PD) is a neurodegenerative disorder involving the loss of dopaminergic neurons in the brain. Following the discovery of the PD-causing D620N mutation in the VPS35 (Vacuolar sorting protein 35) gene, dysfunction in the subcellular retromer complex has been strongly implicated in pathogenesis of PD. Although the function and dysfunction of the retromer has been a focus of study for some time, the role of this complex in the development of PD is not fully understood. Investigating cellular alterations that occur when the retromer is rendered dysfunctional, such as when the D620N disease-causing mutation is introduced into various model systems, shows that endosomal processing defects are major contributors to the disease phenotype. Altered trafficking of retromer cargo molecules, reduced cellular survival and altered processing of alpha-synuclein have all been observed in the presence of the D620N mutation. In addition, interactions between the retromer and the protein products of other familial Parkinsonism-related genes, has made the retromer a prime target of research in PD. This review gives an overview of the changes in retromer function, identified thus far, that may contribute to the neurodegeneration observed in PD.
10.1016/j.parkreldis.2016.12.001
Inflammation in Parkinson's disease.
Wüllner U,Klockgether T
Journal of neurology
Several studies of Parkinson's disease (PD) patients and experimental models of PD indicate the presence of an inflammatory process in PD. Although the primary cellular mechanisms remain to be clarified, activation of resident microglia appears to aggravate or even maintain the disease process in PD. Modulation of inflammatory mechanisms could provide a new neuroprotective therapy in PD.
10.1007/s00415-003-1107-x
Biomarkers in Parkinson's disease: an update.
Shtilbans Alexander,Henchcliffe Claire
Current opinion in neurology
PURPOSE OF REVIEW:This review article is focused upon the most recent biomarker studies of Parkinson's disease. It provides an update on promising areas of biomarker research in a rapidly expanding field, and discusses future directions that might lead to successful development of Parkinson's disease biomarkers. RECENT FINDINGS:Studies of molecular-genetic and biochemical biomarkers of Parkinson's disease have not only targeted hypothesis-driven measures of specific substrates involved in processes such as protein misprocessing, but also have made use of sophisticated analyses such as transcriptomic, proteomic, and metabolomic approaches. Whereas none of these are yet established as Parkinson's disease biomarkers, brain imaging using the 123I-ioflupane ligand with single-photon emission computed tomography was recently approved in the United States to aid in Parkinson's disease diagnosis, and research on other imaging modalities is ongoing. Neurophysiological tests are also being adapted for biomarker research, and we review recent promising data. SUMMARY:The search for effective biomarkers for diagnosis and surveillance of Parkinson's disease continues. A battery of biomarkers comprising different modalities might be required to address clinical needs in this complex disorder. Critically, collaborative efforts including centralized tissue repository and clinical research infrastructure that are being organized will advance this field further.
10.1097/WCO.0b013e3283550c0d
Physical therapy in Parkinson's disease: evolution and future challenges.
Keus Samyra H J,Munneke Marten,Nijkrake Maarten J,Kwakkel Gert,Bloem Bastiaan R
Movement disorders : official journal of the Movement Disorder Society
Even with optimal medical management using drugs or neurosurgery, patients with Parkinson's disease (PD) are faced with progressively increasing mobility problems. For this reason, many patients require additional physical therapy. Here, we review the professional evolution and scientific validation of physical therapy in PD, and highlight several future challenges. To gain insight in ongoing, recently completed or published trials and systematic reviews, we performed a structured literature review and contacted experts in the field of physical therapy in PD. Following publication of the first controlled clinical trial in 1981, the quantity and quality of clinical trials evaluating the efficacy of physical therapy in PD has evolved rapidly. In 2004 the first guideline on physical therapy in PD was published, providing recommendations for evidence-based interventions. Current research is aiming to gather additional evidence to support specific intervention strategies such as the prevention of falls, and to evaluate the implementation of evidence into clinical practice. Although research focused on physical therapy for PD is a relatively young field, high-quality supportive evidence is emerging for specific therapeutic strategies. We provide some recommendations for future research, and discuss innovative strategies to improve the organization of allied health care in PD, making evidence-based care available to all PD patients.
10.1002/mds.22141
Recalling the pathology of Parkinson's disease; lacking exact figure of prevalence and genetic evidence in Asia with an alarming outcome: A time to step-up.
Mahmood Arif,Shah Abid Ali,Umair Muhammad,Wu Yiming,Khan Amjad
Clinical genetics
Parkinson's disease (PD) is the second most common and progressive neurodegenerative disease globally, with major symptoms like bradykinesia, impaired posture, and tremor. Several genetic and environmental factors have been identified but elucidating the main factors have been challenging due to the disease's complex nature. Diagnosis, prognosis, and management of such diseases are challenging and require effective targeted attention in developing countries. Recently, PD is growing rapidly in many crowded Asian countries as an alarming threat with inadequate knowledge of its prevalence, genetic architecture, and geographic distribution. This study gave an in-depth overview of the prevalence, incidence and genomic/genetics studies published so far in the Asian population. To the best of our knowledge, PD has increased significantly in several Asian countries, including China, South Korea, Japan, Thailand, and Israel over the past few years, requiring a greater level of care and attention. Genetic screening of families with PD at national levels and establishing an official database of PD cases are essential to get a comprehensive and conclusive view of the exact prevalence and genetic diversity of PD in the Asian population to properly manage and treat the disease.
10.1111/cge.14019
The pathophysiological mechanisms of motivational deficits in Parkinson's disease.
Chagraoui A,Boukhzar L,Thibaut F,Anouar Y,Maltête D
Progress in neuro-psychopharmacology & biological psychiatry
Parkinson's disease (PD) is a progressive degenerative disorder that leads to disabling motor symptoms and a wide variety of neuropsychiatric symptoms. Apathy is the most common psychiatric disorder in the early stages of untreated PD and can be defined as a hypodopaminergic syndrome, which also includes anxiety and depression. Apathy is also considered the core feature of the parkinsonian triad (apathy, anxiety and depression) of behavioural non-motor signs, including a motivational deficit. Moreover, apathy is recognised as a distinct chronic neuropsychiatric behavioural disorder based on specific diagnostic criteria. Given the prevalence of apathy in approximately 40% of the general Parkinson's disease population, this appears to be a contributing factor to dementia in PD; also, apathy symptoms are factors that potentially contribute to morbidity, leading to a major impairment of health-related quality of life, thus stressing the importance of understanding the pathophysiology of this disease. Several studies have clearly established a prominent role for DA-mediated signals in PD apathy. However, synergistic interaction between dopaminergic impairment resulting from the neurodegenerative process and deep brain stimulation of the subthalamic nucleus may cause or exacerbate apathy. Furthermore, serotoninergic mechanism signalling is also likely to be of importance in this pathophysiology.
10.1016/j.pnpbp.2017.10.022
What Engineering Technology Could Do for Quality of Life in Parkinson's Disease: A Review of Current Needs and Opportunities.
Stamford Jonathan A,Schmidt Peter N,Friedl Karl E
IEEE journal of biomedical and health informatics
Parkinson's disease (PD) involves well-known motor symptoms such as tremor, rigidity, bradykinesia, and altered gait, but there are also nonlocomotory motor symptoms (e.g., changes in handwriting and speech) and even nonmotor symptoms (e.g., disrupted sleep, depression) that can be measured, monitored, and possibly better managed through activity-based monitoring technologies. This will enhance quality of life (QoL) in PD through improved self-monitoring and also provide information that could be shared with a healthcare provider to help better manage treatment. Until recently, nonmotor symptoms ("soft signs") had been generally overlooked in clinical management, yet these are of primary importance to patients and their QoL. Day-to-day variability of the condition, the high variability in symptoms between patients, and the isolated snapshots of a patient in periodic clinic visits make better monitoring essential to the proper management of PD. Continuously monitored patterns of activity, social interactions, and daily activities could provide a rich source of information on status changes, guiding self-correction and clinical management. The same tools can be useful in earlier detection of PD and will improve clinical studies. Remote medical communications in the form of telemedicine, sophisticated tracking of medication use, and assistive technologies that directly compensate for disease-related challenges are examples of other near-term technology solutions to PD problems. Ultimately, a sensor technology is not good if it is not used. The Parkinson's community is a sophisticated early adopter of useful technologies and a group for which engineers can provide near-term gratifying benefits.
10.1109/JBHI.2015.2464354
Prevention of falls in Parkinson's disease: a review of fall risk factors and the role of physical interventions.
Canning Colleen G,Paul Serene S,Nieuwboer Alice
Neurodegenerative disease management
Falls in people with Parkinson's disease (PD) are frequent and recurrent events with devastating and widespread consequences. Despite this, understanding of the predictive and explanatory value of fall risk factors, as well as the development and testing of interventions aimed at reducing falls, are in their infancy. This review focuses on fall prediction and risk factors that are potentially remediable with physical interventions. We show that falls can be predicted with high accuracy using a simple three-step clinical tool. Evidence from recently published randomized controlled trials supports the implementation of balance-challenging exercises in reducing falls. Larger scale trials utilizing technologically advanced monitoring methods will further elucidate those interventions most likely to be cost effective according to individual risk factor profiles.
10.2217/nmt.14.22
Delivering patient-centered care in Parkinson's disease: Challenges and consensus from an international panel.
Bhidayasiri Roongroj,Panyakaew Pattamon,Trenkwalder Claudia,Jeon Beomseok,Hattori Nobutaka,Jagota Priya,Wu Yih-Ru,Moro Elena,Lim Shen-Yang,Shang Huifang,Rosales Raymond,Lee Jee-Young,Thit Win Min,Tan Eng-King,Lim Thien Thien,Tran Ngoc Tai,Binh Nguyen Thanh,Phoumindr Appasone,Boonmongkol Thanatat,Phokaewvarangkul Onanong,Thongchuam Yuwadee,Vorachit Somchit,Plengsri Rachaneewan,Chokpatcharavate Marisa,Fernandez Hubert H
Parkinsonism & related disorders
An international panel of movement disorders specialists explored the views and perceptions of people with Parkinson's disease (PD) about their condition and its treatment, including the potential mismatch between the clinician's view of the patient's condition and their own view of what aspects of the disease most affect their daily lives. The initiative was focused on Asian countries, so participants comprised experts in the management of PD from key centers in Asia, with additional insight provided by European and the North American movement disorders experts. Analysis of peer-reviewed publications on patient perceptions of PD and the factors that they consider important to their wellbeing identified several contributing factors to the mismatch of views, including gaps in knowledge of PD and its treatment, an understanding of the clinical heterogeneity of PD, and the importance of a multidisciplinary approach to patient care. The faculty proposed options to bridge these gaps to ensure that PD patients receive the personalized treatment they need to achieve the best possible outcomes. It was considered essential to improve patient knowledge about PD and its treatment, as well as increasing the awareness of clinicians of PD heterogeneity in presentation and treatment response. A multidisciplinary and shared-care approach to PD was needed alongside the use of patient-centered outcome measures in clinical trials and clinical practice to better capture the patient experience and improve the delivery of individualized therapy.
10.1016/j.parkreldis.2020.02.013
Pathophysiology of Parkinson's disease.
Bonnet A M,Houeto J L
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Parkinson's disease is a progressive disease with selective dopaminergic neuronal loss. The pathophysiology is at present better understood with plurifactorial etiology, including genetic predisposition and environmental toxic factors. The mechanisms of cell death are based upon oxidative stress and apoptosis. The heterogeneity of dopaminergic neuronal loss leads to etiopathogenic clues. In the same way, the model of functional organization of basal ganglia circuitry gives a basis for further experimental and therapeutic research.
10.1016/S0753-3322(99)80076-6
[Psychosis in Parkinson's disease].
Rongve Arvid,Auning Eirik,Ehrt Uwe,Arsland Dag
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke
BACKGROUND:Psychosis is common in Parkinson's disease, and occurs with increasing frequency as the disease progresses. Assessment and treatment are often complicated and involve several clinical specialists in addition to the general practitioner. We describe the prevalence, form, causes and treatment of psychosis in Parkinson's disease. MATERIAL AND METHOD:The article is based on a literature search in PubMed for controlled pharmacological treatment studies and a discretionary selection of articles based on the authors' clinical and research experience. RESULTS:About 1 % of patients with newly diagnosed Parkinson's disease have psychotic symptoms. In later stages, complicated by dementia, these symptoms occur in about half of the patients. A false sense of presence, optical illusions and visual hallucinations occur most frequently, but delusions and hallucinations involving other senses have been reported. Various theories to explain the underlying etiology and pathology are explored. A further medical assessment is recommended when psychotic symptoms occur. Clozapine is still the only antipsychotic drug documented effective against psychotic symptoms in Parkinson's disease. INTERPRETATION:The prevalence of psychotic symptoms in various stages of Parkinson''s disease has been thoroughly documented. Non-pharmacological treatment is often effective, but the documentation is inadequate. Pharmacological treatment with clozapine has proved effective against psychosis in Parkinson's disease, but new drugs that are easier to administer are needed.
10.4045/tidsskr.11.0723
Diagnostic markers for Parkinson's disease.
Chahine Lama M,Stern Matthew B
Current opinion in neurology
PURPOSE OF REVIEW:This review enumerates recent developments in the early diagnosis of Parkinson's disease, with an emphasis on detection of preclinical Parkinson's disease. RECENT FINDINGS:Several clinical, laboratory, and imaging tests are now being investigated as potential early markers of Parkinson's disease. These include various nonmotor features that predate the motor manifestations of Parkinson's disease, including sleep abnormalities, neurobehavioral symptoms, and olfactory dysfunction. Tests of the autonomic nervous system, such as cardiac functional imaging, allow for a measure of cardiac sympathetic denervation. Cerebrospinal fluid and serum tests, including α-synuclein and DJ-1, are being developed and refined. Various imaging modalities have contributed to the diagnostic armamentarium in Parkinson's disease, including transcranial Doppler ultrasonography, radiolabeled tracer imaging, and magnetic resonance imaging. Early Parkinson's disease detection will pave the way for major advances in disease modifying therapies. SUMMARY:Various diagnostic modalities hold promise for the early and preclinical diagnosis of Parkinson's disease. It is likely that the future diagnosis of Parkinson's disease will rely on a combination of clinical, laboratory, imaging, and genetic data.
10.1097/WCO.0b013e3283461723
Parkinson's disease: current and future challenges.
Langston J William
Neurotoxicology
In 15 years, we will mark the 200th anniversary of the James Parkinson's original description of the disease that now bears his name (An Essay on the Shaking Palsy, Sherwood, Neely and Jones London, 1817). Perhaps, one of the most exciting but daunting questions we face at this moment is whether or not we can unravel the etiology of the disease by that time. If we are to accomplish such an ambitious goal, we must determine the resources that will be required to make it happen, and identify the areas of scientific focus that should receive the greatest attention. One issue that will have great bearing on the allocation of research resources relates to the relative roles of genes versus environment in disease causation. For reasons that will become clear in this article, this has a remained surprisingly controversial area. Ironically, this controversy has even spilled over to the very definition of Parkinson's disease, and even whether or not it should be considered a disease entity. In this article, the enduring "genes versus environment" debate is reviewed, with a goal of putting it into a broader perspective. Issues surrounding disease definition and terminology are also addressed in detail, because of the need to have clarity of thought and vision if research on the cause is to proceed in an orderly (and hopefully expeditious) manner. Finally, issues relating future research directions are summarized, with the goal of identifying the pieces of the Parkinson's puzzle that are going to have to be put together if we are to solve this mysterious disease.
10.1016/s0161-813x(02)00098-0
Wearable technological platform for multidomain diagnostic and exercise interventions in Parkinson's disease.
Hu Bin,Chomiak Taylor
International review of neurobiology
Physical activity and exercise have become a central component of medical management of chronic illness, particular for the elderly who suffer from neurodegenerative disorders that impair their cognition and mobility. This chapter summarizes our recent research showing that a new generation of wearable technology can be adopted as diagnostic and rehabilitation tools for people living with Parkinson's disease. For example, wearable device-enabled 6-min walking test can be automated to eliminate human supervision and many other technical factors that confound the results with conventional testing. With reduced cost and increased test standardization, the technology can be adopted for population-based screening of cardiovascular fitness and gait rehabilitation training efficacy associated with many medical conditions. The Ambulosono platform for multidomain exercise intervention, in particular, has the potential to deliver lasting clinical benefits in slowing PD progression. The platform, through the integration of brisk walking with behavioral shaping strategies such as contingency reinforcement, anticipatory motor control and musical motivational stimulation, creates a home exercise regime that can transform monotonous walking into a pleasurable daily activity and habit.
10.1016/bs.irn.2019.08.004
Is apathy a valid and meaningful symptom or syndrome in Parkinson's disease? A critical review.
Bogart Kathleen Rives
Health psychology : official journal of the Division of Health Psychology, American Psychological Association
OBJECTIVE:To review the nearly 30 papers suggesting that apathy may occur frequently in Parkinson's disease (PD) and that it may be a symptom or syndrome that is separate from depression. METHOD:Literature review. RESULTS:The review revealed three possible explanations for the high rates of apathy found in PD. First, there is much interest in an endogenous explanation of apathy because the basal ganglia and dopamine are implicated in both PD and apathy. Researchers have suggested links between apathy, dopamine depletion, and basal ganglia dysfunction in PD. Second, apathy in PD may be exogenous, resulting from disability and activity restriction. Third, apathy findings are inflated due to conceptual problems and methodological confounds. Indeed, apathy may be consistently confounded with symptoms of PD, including expressive masking, depression, disability, and cognitive decline. CONCLUSION:Because apathy has not yet been found to relate to meaningful patient outcomes, and it appears that other factors such as depression and cognition are more strongly related to quality of life than apathy, there is not enough evidence to conclude that apathy is a clinically meaningful syndrome in PD. The role of PD in motivation is of theoretical and practical interest and deserves further research.
10.1037/a0022851
What can biomarkers tell us about cognition in Parkinson's disease?
Mollenhauer Brit,Rochester Lynn,Chen-Plotkin Alice,Brooks David
Movement disorders : official journal of the Movement Disorder Society
Cognitive decline is common in Parkinson's disease (PD), even in the early motor stage, and this non-motor feature impacts quality of life and prognosis tremendously. In this article, we discuss marker candidates for cognitive decline in PD from different angles, including functional and structural imaging techniques, biological fluid markers in cerebrospinal fluid, and blood genetic predictors, as well as gait as a surrogate marker of cognitive decline. Specifically, imaging-based markers of cognitive impairment in PD include cortical atrophy, reduced cortical metabolism, loss of cortical cholinergic and frontal dopaminergic function, as well as an increased cortical amyloid load. Reduced β-amyloid(1-42) in cerebrospinal fluid and lower plasma levels of epidermal growth factor are predictors for cognitive decline in PD. In addition, genetic variation in the apolipoprotein E (APOE), catechol-O-methyltransferase (COMT), microtubule-associated protein tau (MAPT), and glucocerebrosidase (GBA) genes may confer risk for cognitive impairment in PD; and gait disturbance may also indicate an increased risk for dementia. Other marker candidates have been proposed and are discussed. All of the current studies are hampered by gaps in our knowledge about the molecular causes of cognitive decline, which will have to be considered in future biomarker studies.
10.1002/mds.25846
Challenges in detecting disease modification in Parkinson's disease clinical trials.
Athauda Dilan,Foltynie Thomas
Parkinsonism & related disorders
Despite the wealth of encouraging data from numerous compounds that demonstrate "neuroprotection" in pre-clinical studies of Parkinson's disease, and despite numerous clinical trials, to date, no intervention has been demonstrated to able to modify the course of disease progression. While this "failure to translate" is likely due to numerous factors including our incomplete understanding of the pathogenic mechanisms underlying PD together with excessive reliance on data from the toxin-based animal models of PD, here we will discuss the "structural issues" pertaining to inadequate clinical trial design, selection of inappropriate endpoints and poor patient selection which are often not addressed following failed disease modification trials. Future directions to overcome these challenges such as reducing the heterogeneity of patient cohorts, identifying and utilising a pre-diagnostic population, embracing a personalised medicine approach and utilising novel trial designs may be required to ultimately fulfil the goal of conclusively demonstrating evidence of disease modification.
10.1016/j.parkreldis.2016.07.019
Serotonin transporter in Parkinson's disease: A meta-analysis of positron emission tomography studies.
Pagano Gennaro,Niccolini Flavia,Fusar-Poli Paolo,Politis Marios
Annals of neurology
Positron emission tomography (PET) is a powerful analytical tool for in vivo molecular imaging of the human brain. Over the past years, a number of PET studies imaging the serotonin transporter (SERT) have been used and provided evidence for the key role of serotonergic pathology in patients with Parkinson's disease (PD). Here, we review the role of SERT in the development of motor and nonmotor complications in patients with PD, and we performed a meta-analysis to identify the patterns of SERT pathology and the relevance to symptoms. Consistent SERT pathology in raphe nuclei, striatum, thalamus, and hypothalamus and associations with aging, PD progression, development of dyskinesias, and cognitive decline were observed. Ann Neurol 2017;81:171-180.
10.1002/ana.24859
Efficacy of non-pharmacological interventions on depressive symptoms in patients with Parkinson's disease: a study protocol for a systematic review and network meta-analysis.
BMJ open
INTRODUCTION:Depression is the most dominant non-motor symptom of Parkinson's disease (PD), with a prevalence of up to 50%, and can lead to a range of psychiatric and psychological problems that can affect quality of life and overall functioning. While several randomised controlled trials (RCTs) have tested the effect of certain non-pharmacological interventions on the outcome of PD depression symptoms, the comparative benefits and harms of these remain unclear. We will conduct a systematic review and network meta-analysis to compare the efficacy and safety of different non-pharmacological interventions for patients with PD depression. METHODS AND ANALYSIS:We will search PubMed, Web of Science, Cochrane, Embase, Google Scholar, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, WanFang Data and the Chongqing VIP Database from their inception date to June 2022. The studies will be limited to results published in English or Chinese. The primary outcomes will be the changes in the depressive symptoms, while secondary outcomes will include adverse effects and the quality of life. Two researchers will screen those documents that meet the inclusion criteria, extracting data according to the preset table and evaluating the methodological quality of the included studies using the Cochrane Risk of Bias 2.0 Tool. The STATA and ADDIS statistical software will be used to conduct a systematic review and network meta-analysis. A traditional pairwise meta-analysis and a network meta-analysis will be performed to compare the efficacy and safety of different non-pharmacological interventions, ensuring the robustness of the findings. The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the overall quality of the body of evidence associated with the main results. The publication bias assessment will be conducted using comparison-adjusted funnel plots. ETHICS AND DISSEMINATION:All the data for this study will be extracted from published RCTs. As a literature-based systematic review, this study does not require ethical approval. The results will be disseminated through peer-reviewed journals and national/international conference presentations. PROSPERO REGISTRATION NUMBER:CRD42022347772.
10.1136/bmjopen-2022-068019
Parkinson's disease: aetiology, diagnosis, and management.
Leung H,Mok V
Hong Kong medical journal = Xianggang yi xue za zhi
OBJECTIVE:To review the aetiology, diagnosis, and management of Parkinson's disease, with a local perspective. DATA SOURCES:Medline from 1966 onwards, and all major neurological journals and movement disorder journals were searched for evidence on the aetiology, diagnosis, and management of Parkinson's disease. STUDY SELECTION:Key words for the literature search were "Parkinson's disease" and "Chinese" or "Hong Kong". DATA EXTRACTION:All relevant articles in English were reviewed. DATA SYNTHESIS:The number of promising genes for familial Parkinson's disease is still expanding rapidly and there has been a wealth of studies on susceptibility genes for Parkinson's disease. Potential treatment choices include the use of agents thought to be neuroprotective, symptomatic treatment with drugs or surgery, and non-pharmacological treatments. Pharmacological treatment using a dopa-sparing strategy and continuous dopaminergic stimulation is now gaining support to address the issue of long-term motor complications. Surgical treatment with deep brain stimulation is safe and effective for refractory cases and has been increasingly utilised locally. CONCLUSIONS:Medical therapy remains the mainstay of treatment and newer agents and treatment approaches are emerging, which will hopefully address the issue of neuroprotection and provide symptomatic treatment with fewer motor complications.
GLP-1 and GIP receptor agonists in the treatment of Parkinson's disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies.
PloS one
BACKGROUND:Parkinson's disease (PD) is a progressive multifactorial neurodegenerative condition. Epidemiological studies have shown that patients with type 2 diabetes mellitus (T2DM2) are at increased risk for developing PD, indicating a possible insulin-modulating role in this latter condition. We hypothesized that drugs similar to glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), used in the treatment of T2DM2, may play a role in PD. OBJECTIVES:The purpose of this study is to systematically review and meta-analyze data of preclinical and clinical studies evaluating the efficacy and safety of GLP-1 and GIP drugs in the treatment of PD. METHODS:Two reviewers will independently evaluate the studies available in the Ovid Medline, Ovid Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cinahl, and Lilacs databases. Preclinical rodent or non-human primate studies and randomized controlled human clinical trials will be included, without language or publication period restrictions. Outcomes of interest in preclinical studies will be primarily locomotor improvements and adverse effects in animal models of PD. For clinical trials, we will evaluate clinical improvements rated by the Movement Disorders Society Unified Parkinson's Disease Rating Scale-parts I, II, III, and IV, and adverse effects. The risk of bias of preclinical studies will be assessed by the SYRCLE tool and CAMARADES checklist and the clinical studies by the Cochrane tool; the certainty of the evidence will be rated by GRADE. DISCUSSION AND CONCLUSION:There is an urge for new PD treatments that may slow the progression of the disease rather than just restoring dopamine levels. This study will comprehensively review and update the state of the art of what is known about incretin hormones and PD and highlight the strengths and limitations of translating preclinical data to the clinic whenever possible. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration number CRD42020223435.
10.1371/journal.pone.0255726
Skin alpha-synuclein deposit patterns: A predictor of Parkinson's disease subtypes.
EBioMedicine
Parkinson's disease (PD) is a neurodegenerative disease characterized pathologically by the formation of Lewy bodies comprised mainly of α-synuclein. Assessment of skin synuclein has the potential as an excellent diagnostic method with high sensitivity, specificity, and reproducibility that is also convenient and acceptable to patients. In this review, we summarize findings regarding the characteristics of cutaneous nerve p-α-syn or α-syn deposits and their correlations with clinical phenotypes in PD patients with and without orthostatic hypotension and LRRK2, GBA, and SNCA gene mutations. This review can serve as a reference for the diagnosis and classification of PD based on α-syn deposit patterns and to deeply explore its pathogenesis. FUNDING STATEMENT: The work was partly supported by the National Natural Science Key Foundation of China (No. 81830040 and No 82130042) and the Program of Excellent Talents in Medical Science of Jiangsu Province (No. JCRCA2016006) .
10.1016/j.ebiom.2022.104076
The Association Between Vitamin D Status, Vitamin D Supplementation, Sunlight Exposure, and Parkinson's Disease: A Systematic Review and Meta-Analysis.
Medical science monitor : international medical journal of experimental and clinical research
BACKGROUND This literature review and meta-analysis aimed to determine the association between deficiency of vitamin D, or 25-hydroxyvitamin D, and Parkinson's disease, and whether vitamin D from supplements and sunlight improves the symptoms of Parkinson's disease. MATERIAL AND METHODS A literature review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Systematic literature review was performed using databases that included the Web of Science, PubMed, the Cochrane Library, and Embase. The Jadad scale (the Oxford quality scoring system) and the Newcastle-Ottawa scale (NOS) were used to evaluate the quality of the studies. RESULTS Eight studies were included in the meta-analysis. Both 25-hydroxyvitamin D insufficiency (<30 ng/mL) (OR, 1.77; 95% CI, 1.29-2.43; P<0.001) and deficiency (<20 ng/mL) (OR, 2.55; 95% CI, 1.98-3.27; P<0.001) were significantly associated with an increased risk of Parkinson's disease when compared with normal controls Sunlight exposure (³15 min/week) was significantly associated with a reduced risk of Parkinson's disease (OR, 0.02; 95% CI, 0.00-0.10; P<0.001). The use of vitamin D supplements was effective in increasing 25-hydroxyvitamin D levels (SMD, 1.79; 95% CI, 1.40-2.18; P<0.001), but had no significant effect on motor function (MD, -1.82; 95% CI, -5.10-1.45; P=0.275) in patients with Parkinson's disease. CONCLUSIONS Insufficiency and deficiency of 25-hydroxyvitamin D and reduced exposure to sunlight were significantly associated with an increased risk of Parkinson's disease. However, vitamin D supplements resulted in no significant benefits in improving motor function for patients with Parkinson's disease.
10.12659/MSM.912840
Designing environments that contribute to a reduction in the progression of Parkinson's disease; a literature review.
Health & place
Parkinson's Disease (PD), a prevalent neurological disorder, causes physical difficulties like stiffness and impaired walking and affects patients' emotional well-being. Regular exercise and exposure to enriched environments are crucial to managing these symptoms. This review aims to extract evidence from studies regarding built environments' impact on reducing the progression of PD. Keywords from 2005 to 2022 were used in five databases, including PubMed, Clarivate Web of Science, UGA Library, and Google Scholar. Many studies emphasized physiotherapy and training for physical enhancement, often utilizing virtual games and smart devices. Others highlighted the advantages of non-slip flooring and accessible outdoor spaces, with some based on universal design principles. Few studies considered the emotional impact of built environments, showing a considerable gap in the studies simultaneously evaluating psychological and physical perspectives of Parkinson-friendly environments. There needs to be more consistency when considering these aspects of planning. Our findings suggest future research modeling enriched environments and tracking their impact on patients via Virtual Reality to find a comprehensive guideline for the most effective PD management environments.
10.1016/j.healthplace.2023.103105
Saccadic eye movements in Parkinson's disease.
Srivastava Anshul,Sharma Ratna,Sood Sanjay K,Shukla Garima,Goyal Vinay,Behari Madhuri
Indian journal of ophthalmology
This review focuses on saccadic eye movement research in Parkinson's disease (PD) patients. Results from various studies related to Parkinson disease and saccades have been discussed in terms of various saccadic parameters like latency, amplitude, velocity and gain. Neural circuitry of saccadic eye movements and cognitive processes and it's relation with altered saccadic performance in Parkinson disease has been discussed here. This article also covers various research paradigms commonly used to study saccades. Effects of medication on saccadic parameters in PD patients have also been discussed along with the effects of deep brain stimulation of subthalamic nucleus on saccadic performance in PD patients. Literature review was done using online Pubmed search engine and National Medical Library.
10.4103/0301-4738.133482
Treatment of Parkinson's disease.
Aminoff M J
The Western journal of medicine
Pharmacotherapy with levodopa for Parkinson's disease provides symptomatic benefit, but fluctuations in (or loss of) response may eventually occur. Dopamine agonists are also helpful and, when taken with low doses of levodopa, often provide sustained benefit with fewer side effects; novel agonists and new methods for their administration are therefore under study. Other therapeutic strategies are being explored, including the use of type B monoamine oxidase inhibitors to reduce the metabolic breakdown of dopamine, catechol-O-methyltransferase inhibitors to retard the breakdown of levodopa, norepinephrine precursors to compensate for deficiency of this neurotransmitter, glutamate antagonists to counteract the effects of the subthalamic nucleus, and various neurotrophic factors to influence dopaminergic nigrostriatal cells. Surgical procedures involving pallidotomy are sometimes helpful. Those involving cerebral transplantation of adrenal medullary or fetal mesencephalic tissue have yielded mixed results; benefits may relate to the presence of growth factors in the transplanted tissue. The transplantation of genetically engineered cell lines will probably become the optimal transplantation procedure. The cause of Parkinson's disease may relate to oxidant stress and the generation of free radicals. It is not clear whether treatment with selegiline hydrochloride (a type B monoamine oxidase inhibitor) delays the progression of Parkinson's disease, because the drug also exerts a mild symptomatic effect. Daily treatment with vitamin E (a scavenger of free radicals) does not influence disease progression, perhaps because of limited penetration into the brain.
Initial treatment of Parkinson's disease in 2016: The 2000 consensus conference revisited.
Laurencin C,Danaila T,Broussolle E,Thobois S
Revue neurologique
In 2000, a French consensus conference proposed guidelines for the treatment of Parkinson's disease (PD). Since then, new drugs have been concocted, new studies have been published and clinicians have become aware of some drug-induced adverse effects that were little known in the past. This has led us to reconsider the recommendations published 16 years ago. Thus, the aim of the present review is to present the recent data related to the different medications and non-pharmacological approaches available for PD, with a special focus on early-stage PD. Levodopa (LD), dopamine agonists (DAs), catechol-O-methyltransferase inhibitors (COMT-Is), anticholinergics, monoamine oxidase inhibitors (MAOB-Is) and amantadine have been considered, and their efficacy and safety for both motor as well as non-motor aspects are reported here. This has led to our proposal for a revised therapeutic strategy for the initiation of treatment in newly diagnosed PD patients, based on the available literature and the relative benefits/side effects balance.
10.1016/j.neurol.2016.07.007
A review of Parkinson's disease.
Davie C A
British medical bulletin
INTRODUCTION:Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Sources of data Literature search using Medline with keywords Parkinson's disease supplemented with previously published papers known to the author. AREAS OF AGREEMENT:There have been significant recent advances in the understanding of the pathogenesis of the disease. There has also been a greater realization that the disorder may be associated with significant non-motor disturbances in addition to the more commonly recognized motor complications. AREAS OF CONTROVERSY:Although there is growing circumstantial evidence, it remains to be proven whether any of the current treatments for PD have a neuroprotective effect. AREAS TIMELY FOR DEVELOPING RESEARCH:Although there is no cure, there are several management options for the early treatment of PD. As the disease progresses, further treatment options are available; however, the management of late-stage motor complications and non-motor symptoms remains particularly challenging and will benefit from further clinical research.
10.1093/bmb/ldn013
Efficacy and safety of treatments for REM sleep behaviour disorder in Parkinson's disease: a systematic review and Bayesian network meta-analysis protocol.
Lin Fabin,Weng Yanhong,Lin Xiaofeng,Wu Dihang,Su Yixiao,Cai Guoen
BMJ open
INTRODUCTION:Sleep disorders are the main non-motor characteristics of Parkinson's disease (PD). The quality of life is significantly impacted by rapid eye movement sleep behaviour disorder (RBD). It is not clearly evidenced in the literature that some medications can reduce the dream activities of patients with PD and RBD and improve sleep quality. And, they have side effects that may increase the severity of this disease. To further understand which medication has better efficacy and fewer adverse effects for patients with PD and RBD, it is necessary to perform a network meta-analysis. METHODS AND ANALYSIS:This protocol is performed accordingly to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the Cochrane Collaboration Handbook.A thorough literature selection will be conducted up to September 2021 using PubMed, Cochrane Library (The Cochrane Database of Systematic Reviews) and Embase. We will not only include randomised controlled trials, but prospective, retrospective cohort, case-control, nested case-control, case-cohort, cross-sectional and case series. We will use the Cochrane Collaboration tool to assess the risk of bias. Pairwise and network meta-analyses will be conducted using the R netmeta package and Stata V.14.0. The relative ranking probability of the best intervention will be estimated using the surface under the cumulative ranking curve. Additionally, sensitivity analysis, subgroup analysis, quality assessment and publication bias analysis will be performed. ETHICS AND DISSEMINATION:No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence. PROSPERO REGISTRATION NUMBER:CRD42020206958.
10.1136/bmjopen-2020-047934
MiRNAs participate in the diagnosis, pathogenesis and therapy of Parkinson's disease.
Lu Xuexin,Cui Zhijie,Liu Shuang,Yin Feng
Histology and histopathology
MicroRNAs (miRNAs), one kind of post-transcriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes, including Parkinson's disease. At present, the pathogenesis of Parkinson's disease is not clear, although many studies suggest that miRNAs play a very important role in the progress of Parkinsonism. This paper reviews the biological characteristics of miRNAs and summarizes the progress of miRNAs in reference to the diagnosis and pathogenesis of Parkinson's disease. It even considers miRNAs as a potential target for Parkinson's disease therapy.
10.14670/HH-11-944
The Challenge of Disease-Modifying Therapies in Parkinson's Disease: Role of CSF Biomarkers.
Paolini Paoletti Federico,Gaetani Lorenzo,Parnetti Lucilla
Biomolecules
The development of disease modifying strategies in Parkinson's disease (PD) largely depends on the ability to identify suitable populations after accurate diagnostic work-up. Therefore, patient molecular profiling and disease subtyping are mandatory. Thus far, in clinical trials, PD has been considered to be a "single entity". Conversely, in front of the common feature of nigro-striatal degeneration, PD is pathogenically heterogeneous with a series of several biological and molecular pathways that differently contribute to clinical development and progression. Currently available diagnostic criteria for PD mainly rely on clinical features and imaging biomarkers, thus missing to identify the contribution of pathophysiological pathways, also failing to catch abnormalities occurring in the early stages of disease. Cerebrospinal fluid (CSF) is a promising source of biomarkers, with the high potential for reflecting early changes occurring in PD brain. In this review, we provide an overview on CSF biomarkers in PD, discussing their association with different molecular pathways involved either in pathophysiology or progression in detail. Their potential application in the field of disease modifying treatments is also discussed.
10.3390/biom10020335
Unveiling the Role of Cytochrome P450 (2E1) in Human Brain Specifically in Parkinson's Disease - Literature Review.
Shah Amna,Ong Chin Eng,Pan Yan
Current drug metabolism
BACKGROUND:In recent years, the significance of cytochrome P450 enzymes (CYPs) has expanded beyond their role in the liver. Factors such as genetics, environmental toxins, drug biotransformation and underlying diseases mediate the expression of these enzymes. Among the CYP enzymes, CYP2E1, a well-recognized monooxygenase enzyme involved in the metabolism of various endogenous and exogenous substances, plays a crucial role in the brain concerning the development of Parkinson's disease. The expression of CYP2E1 varies in different brain regions making certain regions more vulnerable than others. CYP2E1 expression is inducible which generates tissuedamaging radicals leading to oxidative stress, mitochondrial dysfunction and ultimately neurodegeneration. OBJECTIVE:Less is understood about the role of CYP2E1 in the central nervous system, therefore the purpose of the study was to investigate the relationship between the expression and activity of CYP2E1 enzyme relevant to Parkinson's disease and to identify whether an increase in the expression of CYP2E1 is associated with neurodegeneration. METHODS:The objectives of the study were achieved by implicating an unsystematic integrative literature review approach in which the literature was qualitatively analysed, critically evaluated and a new theory with an overall view of the mechanism was presented. RESULTS:The contribution of CYP2E1 in the development of Parkinson's disease was found to be significant as the negative effects of CYP2E1 overshadowed its protective detoxifying role. CONCLUSION:Overexpression of CYP2E1 seems detrimental to dopaminergic neurons, therefore, to overcome this, a synthetic biochemical is required, which paves the way for further research and development of valuable biomolecules.
10.2174/1389200222666210729115151
[Parkinson's disease: pathogenesis, aetiology, symptoms, diagnostics, and its course].
de Baat C,van Stiphout M A E,Lobbezoo F,van Dijk K D,Berendse H W
Nederlands tijdschrift voor tandheelkunde
Parkinson's disease is a slowly progressive neurodegenerative disorder characterised by motor symptoms, which are accompanied or often even preceded by non-motor symptoms. Pathologically, the disease is characterised by neural degeneration in specific brain regions, including the dopaminergic neurons of the pars compacta of the substantia nigra. At the molecular level, mitochondrial dysfunction, oxidative stress, altered protein handling, and reactive microgliosis contribute to the neural degeneration. Advanced age is a significant risk factor. Men are more often affected by the disease than women. Environmental, life-style and genetic factors are potential aetiological factors. The disease is primarily diagnosed on the basis of clinical features. In clinically uncertain cases, magnetic resonance imaging and dopamine transporter single-photon emission computer tomography can provide additional information. Patients usually die due to comorbidity. Parkinson's disease has also several negative influences on the orofacial system.
10.5177/ntvt.2018.10.18176
Effectiveness of interventions to prevent falls for people with multiple sclerosis, Parkinson's disease and stroke: an umbrella review.
BMC neurology
BACKGROUND:The implementation of condition-specific falls prevention interventions is proving challenging due to lack of critical mass and resources. Given the similarities in falls risk factors across stroke, Parkinson's Disease (PD) and Multiple Sclerosis (MS), the development of an intervention designed for groups comprising of people with these three neurological conditions may provide a pragmatic solution to these challenges. The aims of this umbrella review were to investigate the effectiveness of falls prevention interventions in MS, PD and stroke, and to identify the commonalities and differences between effective interventions for each condition to inform the development of an intervention for mixed neurological groups. METHODS:A systematic literature search was conducted using 15 electronic databases, grey literature searches and hand-screening of reference lists. Systematic reviews of studies investigating the effects of falls prevention interventions in MS, PD and stroke were included. Methodological quality of reviews was assessed using the A MeaSurement Tool to Assess Systematic Reviews 2. A matrix of evidence table was used to assess the degree of overlap. The Grading of Recommendations Assessments, Development and Evaluation framework was used to rate the quality of evidence. Findings were presented through narrative synthesis and a summary of evidence table. RESULTS:Eighteen reviews were included; three investigating effectiveness of falls prevention interventions in MS, 11 in PD, three in stroke, and one in both PD and stroke. Exercise-based interventions were the most commonly investigated for all three conditions, but differences were identified in the content and delivery of these interventions. Low to moderate quality evidence was found for the effectiveness of exercise-based interventions at reducing falls in PD. Best available evidence suggests that exercise is effective at reducing falls in stroke but no evidence of effect was identified in MS. CONCLUSIONS:The findings suggest that exercise-based interventions are effective at reducing falls in PD, however, the evidence for MS and stroke is less conclusive. A strong theoretical rationale remains for the use of exercise-based interventions to address modifiable physiological falls risk factors for people with MS, PD and stroke, supporting the feasibility of a mixed-diagnosis intervention. Given the high overlap and low methodological quality of primary studies, the focus should be on the development of high-quality trials investigating the effectiveness of falls prevention interventions, rather than the publication of further systematic reviews.
10.1186/s12883-021-02402-6
Sex differences in Parkinson's disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics.
Jurado-Coronel Juan Camilo,Cabezas Ricardo,Ávila Rodríguez Marco Fidel,Echeverria Valentina,García-Segura Luis Miguel,Barreto George E
Frontiers in neuroendocrinology
Parkinson's disease (PD) is the second most frequent age-related neurodegenerative disorder. Sex is an important factor in the development of PD, as reflected by the fact that it is more common in men than in women by an approximate ratio of 2:1. Our hypothesis is that differences in PD among men and women are highly determined by sex-dependent differences in the nigrostriatal dopaminergic system, which arise from environmental, hormonal and genetic influences. Sex hormones, specifically estrogens, influence PD pathogenesis and might play an important role in PD differences between men and women. The objective of this review was to discuss the PD physiopathology and point out sex differences in nigrostriatal degeneration, symptoms, genetics, responsiveness to treatments and biochemical and molecular mechanisms among patients suffering from this disease. Finally, we discuss the role estrogens may have on PD sex differences.
10.1016/j.yfrne.2017.09.002
Mild parkinsonian features in dystonia: Literature review, mechanisms and clinical perspectives.
Haggstrom Lucy,Darveniza Paul,Tisch Stephen
Parkinsonism & related disorders
Dystonia is a hyperkinetic movement disorder that can be highly stigmatizing and disabling. Substantial evidence from animal models, neuropathological, neurophysiological, neuroimaging and clinical studies emphasizes the role of dopaminergic dysfunction in the pathophysiology of dystonia, illustrating possible pathophysiological overlap with parkinsonism. Furthermore, basal ganglia dysfunction has been implicated in the pathogenesis of dystonia, and is well established to underlie the manifestations of Parkinson's disease. Clinically, parkinsonian features are a key characteristic of some combined dystonias, including dopa-responsive dystonia, and Parkinson's disease often presents with dystonia. Moreover, many treatments effective in Parkinson's disease, both medical and surgical, also offer some benefit in dystonia. Therefore, mild parkinsonian features might logically accompany idiopathic and inherited isolated dystonias. However, as the current literature is particularly scant, the present review aimed to investigate mild parkinsonism in idiopathic and inherited dystonia. We found limited evidence alluding to the presence of mildly reduced arm-swing, increased tone, and non-decremental bradykinesia in adult-onset focal dystonia. Tremor, with postures, action and rest, also occurs commonly in idiopathic isolated dystonia, and can simulate Parkinson's disease tremor and be a cause of 'scans without evidence of dopaminergic deficit'. Parkinsonian features in monogenic isolated dystonias have been less well investigated, despite the potential benefit of correlating pathophysiological and clinical findings. The recognition and improved clinical characterization of parkinsonian features in idiopathic and inherited isolated dystonia extends the clinical spectrum of motor features in dystonia, which may help avoid incorrect diagnosis and inform therapeutic research.
10.1016/j.parkreldis.2016.10.022
Parkinson's disease: diagnosis and treatment.
Rao Shobha S,Hofmann Laura A,Shakil Amer
American family physician
Parkinson's disease is a common neurodegenerative disorder that can cause significant disability and decreased quality of life. The cardinal physical signs of the disease are distal resting tremor, rigidity, bradykinesia, and asymmetric onset. Levodopa is the primary treatment for Parkinson's disease; however, its long-term use is limited by motor complications and drug-induced dyskinesia. Dopamine agonists are options for initial treatment and have been shown to delay the onset of motor complications. However, dopamine agonists are inferior to levodopa in controlling motor symptoms. After levodopa-related motor complications develop in advanced Parkinson's disease, it is beneficial to initiate adjuvant therapy with dopamine agonists, catechol O-methyltransferase inhibitors, or monoamine oxidase-B inhibitors. Deep brain stimulation of the subthalamic nucleus has been shown to ameliorate symptoms in patients with advanced disease. Depression, dementia, and psychosis are common psychiatric problems associated with Parkinson's disease. Psychosis is usually drug induced and can be managed initially by reducing antiparkinsonian medications. The judicious use of psychoactive agents may be necessary. Consultation with a subspecialist is often required.
An update on the recognition and treatment of autonomic symptoms in Parkinson's disease.
Jost Wolfgang H
Expert review of neurotherapeutics
INTRODUCTION:Parkinson's disease (PD) is characterized by motor, autonomic, and neuropsychiatric symptoms. These occur in varying degrees in all stages of the disease. Among the autonomic disorders, cardiovascular, urogenital, gastrointestinal and thermoregulatory disorders are the most relevant. Within cardiovascular disorders drop of blood pressure after orthostasis and non-dipper behavior are very important; but also the influence of cardiovascular medication. Urgency, nocturia, and incontinence are of particular note within the urological problems. Among the gastrointestinal disturbances, swallowing disorders, gastric emptying disorders and constipation are particularly noteworthy. Areas covered: Autonomic symptoms are inherent in PD, in premotor and all other stages of the disease. In this overview, the current status was summarized taking into account original articles and reviews based on relevance to the field and quality of evidence. Expert commentary: The involvement of the autonomic nervous system in Parkinson's disease is still neglected. Because of the significant effects on the quality of life and even the prognosis, appropriate diagnostics and therapy should be performed at all stages of the disease. Despite intensive scientific work the area is still not sufficiently considered and the relevance in pathology is not yet understood.
10.1080/14737175.2017.1345307
Therapeutic strategies in Parkinson's disease: what we have learned from animal models.
Valadas Jorge S,Vos Melissa,Verstreken Patrik
Annals of the New York Academy of Sciences
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a loss of dopaminergic neurons in the substantia nigra, as well as in other brain areas. The currently available dopamine replacement therapy provides merely symptomatic benefit and is ineffective because habituation and side effects arise relatively quickly. Studying the genetic forms of PD in animal models provides novel insight that allows targeting of specific aspects of this heterogenic disease more specifically. Among others, two important cellular deficits are associated with PD; these deficits relate to (1) synaptic transmission and vesicle trafficking, and (2) mitochondrial function, relating respectively to the dominant and recessive mutations in PD-causing genes. With increased knowledge of PD, the possibility of identifying an efficient, long-lasting treatment is becoming more conceivable, but this can only be done with an increased knowledge of the specific affected cellular mechanisms. This review discusses how discoveries in animal models of PD have clarified the therapeutic potential of pathways disrupted in PD, with a specific focus on synaptic transmission, vesicle trafficking, and mitochondrial function.
10.1111/nyas.12577
The Concept of Prodromal Parkinson's Disease.
Mahlknecht Philipp,Seppi Klaus,Poewe Werner
Journal of Parkinson's disease
Parkinson's disease (PD) is currently clinically defined by a set of cardinal motor features centred on the presence of bradykinesia and at least one additional motor symptom out of tremor, rigidity or postural instability. However, converging evidence from clinical, neuropathological, and imaging research suggests initiation of PD-specific pathology prior to appearance of these classical motor signs. This latent phase of neurodegeneration in PD is of particular relevance in relation to the development of disease-modifying or neuroprotective therapies which would require intervention at the earliest stages of disease. A key challenge in PD research, therefore, is to identify and validate markers for the preclinical and prodromal stages of the illness. Currently, several nonmotor symptoms have been associated with an increased risk to develop PD in otherwise healthy individuals and ongoing research is aimed at validating a variety of candidate PD biomarkers based on imaging, genetic, proteomic, or metabolomic signatures, supplemented by work on tissue markers accessible to minimally invasive biopsies. In fact, the recently defined MDS research criteria for prodromal PD have included combinations of risk and prodromal markers allowing to define target populations of future disease modification trials.
10.3233/JPD-150685
Clinical practice guidelines based on evidence for cognitive-behavioural therapy in Parkinson's disease comorbidities: A literature review.
Zečević Ivan
Clinical psychology & psychotherapy
The purpose of this review is to provide psychologists and other health care professional enough knowledge about available cognitive-behavioural interventions for comorbidities in Parkinson's disease that include depression, anxiety, impulsive disorder, pain, and sleep disturbances. This review has clear clinical practical suggestions how to adapt psychological interventions and techniques to the motor and/or cognitive impairments of patients with Parkinson's disease, based on earlier available research results. Every available research that could be found with the help of search engines from Medline, Springer, PsychINFO, and Google Scholar, which used cognitive-behavioural therapy to treat Parkinson's comorbidities, was cited and explained. Cognitive-behavioural interventions and techniques are presented based on available research results for Parkinson's comorbidities. It is recommended to use treatment plans and interventions that are earlier suggested as efficient in patients with Parkinson's disease. Strongest available research based recommendations are available for depression and anxiety. There are only few available research studies that used cognitive and/or behavioural interventions for pain, impulsive disorder, or sleeping disturbances, except insomnia in Parkinson's disease. Cognitive-behavioural therapy is safe to use and should be adapted to the specific needs of patients and with the scientific approved treatment interventions and techniques. Psychologists should be careful on how they adapt their treatment plan for patients.
10.1002/cpp.2448
The effects of Cannabis on hallucinations in Parkinson's disease patients.
Cravanas Brian,Frei Karen
Journal of the neurological sciences
Cannabis use is on the rise both as medical treatment and recreational use. There is evidence that cannabis can cause hallucinations and psychosis especially with heavy and prolonged use. Parkinson's disease (PD) carries an increased risk for development of hallucinations and psychosis. It is possible that cannabis may exacerbate this risk and result in earlier and greater amounts of hallucinations and psychosis in this vulnerable population. A literature review was performed to determine the answer to that question. Two articles were found which listed the incidence of hallucinations and delusions during the use of cannabis in PD patients. 21.3% or 10 out of 47 patients reported development of hallucinations while treated with cannabis and 2.8% developed delusions. While these numbers are within the range of prevalence of hallucinations and psychosis in PD, the number of studies and patients evaluated are too small to make any definite conclusions pointing to the need for more research in this area.
10.1016/j.jns.2020.117206
Visual illusions in Parkinson's disease: an interview survey of symptomatology.
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society
BACKGROUND:Several types of visual illusions can occur in Parkinson's disease (PD). However, the prevalence and types of specific illusions experienced by patients with PD remain unclear. This study aimed to investigate the types of illusions. METHODS:A questionnaire of visual illusions was developed through a literature review in consultation with clinicians and neurologists. Based on the questionnaire, 40 consecutive patients with PD were asked a series of Yes/No questions regarding 20 types of visual illusions since the onset of PD. If participants answered 'Yes', they were then asked to detail their experience(s). RESULTS:In total, 30 patients with PD had experienced visual illusions since disease onset; among them, 25 were still experiencing them at the time of the study. The most commonly observed illusion types were dysmorphopsia, complex visual illusions, metachromatopsia, and diplopia. Other observed illusions included textural illusions, macropsia, micropsia, teleopsia, pelopsia, kinetopsia, akinetopsia, Zeitraffer/Zeitlupen phenomena, tilt illusion, upside-down illusion, and palinopsia. Additionally, aberrant perception of surface orientation (inclination) was reported, which is yet to be reported in association with any disease. Visual illusions had detrimental effects on the patients' daily lives in some cases. CONCLUSIONS:Systematic interviews regarding the incidence and details of visual illusions experienced by patients with PD could offer important information regarding their quality of life.
10.1111/psyg.12771
Noninvasive Brain Stimulation and Implications for Nonmotor Symptoms in Parkinson's Disease.
Rektorová Irena,Anderková Ľubomíra
International review of neurobiology
Transcranial noninvasive brain stimulation includes both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). TMS uses a rapidly changing magnetic field to induce currents and action potentials in underlying brain tissue, whereas tDCS involves the application of weak electrical currents to modulate neuronal membrane potential. In this chapter, we provide a literature review with a focus on the therapeutic potential of both techniques in the treatment of nonmotor symptoms of Parkinson's disease (PD). On the whole, the results of studies are rather preliminary but promising as they show some positive effects of rTMS and tDCS particularly on depressive symptoms and cognitive dysfunctions in PD. More carefully controlled trials with standardized methodology, adequately sized and well-characterized samples, and the inclusion of multimodal approaches are warranted in the future.
10.1016/bs.irn.2017.05.009
Milestones in Parkinson's disease--clinical and pathologic features.
Halliday Glenda,Lees Andrew,Stern Matthew
Movement disorders : official journal of the Movement Disorder Society
The identification of the widespread deposition of fibrillized α-synuclein in Lewy bodies and Lewy neurites in the brains of patients with Parkinson's disease in 1997 has had a profound impact on how the disease is now conceptualized. The previous focus on the loss of the dopaminergic nigrostriatal system, the concept of subcortical dementia, and the idea that Parkinson's disease was dominated by motor impairment have all given way to research assessing more diverse brain regions, clinical symptoms, and phenotypes. It is now recognized that Parkinson's disease is more than just a loss of midbrain dopaminergic neurons in association with Lewy bodies. There are now several theories on how the disease develops and progresses currently being validated in a variety of studies, although many of these theories have yet to incorporate the phenotypic clinical and pathological changes associated with age. A particularly exciting new area of research involves the cell-to-cell transmission of pathogenic proteins. The recent consensus definition of Parkinson's disease dementia will allow its pathologic substrates to be determined. These advances have progressed to a stage where the preclinical stages of Parkinson's disease and its specific signs and symptoms are being predicted and tested clinically. Such strategies herald a future wave of preventive strategies for Parkinson's disease and its clinical symptoms.
10.1002/mds.23669
Biomarkers for the diagnosis and management of Parkinson's disease.
Waragai Masaaki,Sekiyama Kazunari,Fujita Masayo,Tokuda Takahiko,Hashimoto Makoto
Expert opinion on medical diagnostics
INTRODUCTION:Parkinson's disease (PD) is the most common neurodegenerative disease leading to movement disorders, and is characterized neuropathologically by the progressive loss of dopaminergic neurons, intracellular α-synuclein deposition and the formation of Lewy bodies. The difficulty of making a definitive diagnosis of PD itself, as opposed to other neurodegenerative diseases associated with parkinsonism, is a central issue in clinical PD research. However, recent advances in diagnostic methods, encompassing imaging techniques, genetic testing and measurement of biological markers may permit earlier diagnosis, and thus potentially improved management of PD. AREAS COVERED:In addition to clinical symptoms and imaging techniques, a number of genetic and biological markers obtained from body fluids such as cerebrospinal fluids may hold promise for the early detection of PD. It is often difficult to make an accurate diagnosis and to distinguish PD from other diseases with features of parkinsonism, particularly during the early stages of the disease. In this regard, biomarkers which are specific for PD, in combination with observation of clinical symptoms, may facilitate the early diagnosis and improved management of PD. EXPERT OPINION:Good biomarkers for PD could be helpful for early diagnosis, management and tracking of disease progression. Furthermore, combined analysis using several kinds of biomarkers may allow the detection of preclinical PD, which in turn may facilitate a prevention of disease onset with the use of disease-modifying drugs.
10.1517/17530059.2013.733694
Treatment gaps in Parkinson's disease care in the Philippines.
Jamora Roland Dominic G,Miyasaki Janis M
Neurodegenerative disease management
Neurological services and resources are scarce in low-income and developing countries, such as the Philippines. We looked into the treatment gaps in Parkinson's disease (PD) care in the Philippines in the following areas: epidemiology, healthcare, financial coverage, pharmacotherapy, surgical treatment and manpower. We collected relevant data on the above-mentioned areas. There is no available Philippine data on PD prevalence. Philippine healthcare is paid through user fees at the point of service. The average consultation fee in Manila ranges from US$10.57-31.74. The average minimum daily wage is US$9.39-10.17. Philippine healthcare is devolved to the local government units. Deep brain stimulation surgery is only available in Manila. Most PD medications are available in the Philippines. There are only nine movement disorder specialists for a population of 100.98 million. Gaps and challenges in PD care in the Philippines still exist.
10.2217/nmt-2017-0014
Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson's disease.
Balestrino Roberta,Martinez-Martin Pablo
Journal of the neurological sciences
Parkinson's disease is a complex neurodegenerative disorder characterized by motor and non-motor symptoms, with neuropsychiatric manifestations among the most frequent non-motor symptoms. Health-related quality of life is a patient-reported outcome that reflects the impact of the disease on physical, mental, and social wellbeing, and on other aspects of patient' life. Although older studies on health-related quality of life in Parkinson's disease mainly investigated the role of the motor impairment, recent research focused on non-motor symptoms has highlighted the critical role that behavioural disturbances due to neuropsychiatric symptoms play in determining health related quality of life. A considerable number of studies have demonstrated the importance of depression as a determinant of health-related quality of life in this population, but less evidence is available regarding the role of other neuropsychiatric symptoms such as anxiety, apathy, psychosis, and impulse control disorders. This narrative review analyses recent literature on this topic, focusing on studies in which neuropsychiatric symptoms were investigated as potential determinants of quality of life using regression techniques, including discussion of the assessment tools used.
10.1016/j.jns.2016.12.060
Parkinson's disease and Parkinson's disease psychosis: a perspective on the challenges, treatments, and economic burden.
Fredericks Doral,Norton James C,Atchison Carolyn,Schoenhaus Robert,Pill Michael W
The American journal of managed care
Parkinson's disease (PD) is a progressive neurodegenerative disease associated with a decrease in the neurotransmitter dopamine and characterized by the cardinal motor hallmarks of resting tremor, rigidity, bradykinesia/akinesia, and postural instability. Lesser-known features of PD revolve around nonmotor concerns including psychosis, dementia, sleep disturbances, autonomic dysfunction, and sensory abnormalities. Parkinson's disease psychosis (PDP) contributes significantly to morbidity, mortality, nursing home placement, and quality of life (QOL). PDP management suffers from a lack of safe, effective pharmacological agents and the opposing nature of atypical antipsychotics and dopaminergic therapies. Pimavanserin, the only atypical antipsychotic currently approved by the FDA for treating PDP-related hallucinations and delusions, has no appreciable affinity for dopaminergic receptors, and a controlled clinical study demonstrated its efficacy in treating PDP-associated hallucinations and delusions without affecting motor function. A recent analysis of all health resource utilization (HRU) and total costs attributable to PD and PDP found that mean 12-month HRU services per patient were 2.3 times higher and costs were 2.1 times higher in the PDP cases, while falls were 3.4 times higher and fractures 2.3 times higher, respectively. Products or services that prevent, delay, or lessen the severity of PDP may contribute to reduced healthcare system costs and improve the QOL of patients with PDP and of their caregivers.
Dementia with Lewy Bodies and Parkinson Disease Dementia: It is the Same Disease!
Friedman Joseph H
Parkinsonism & related disorders
INTRODUCTION:The question whether DLB and PDD are distinct disorders has been debated in several forums. The two disorders, once parkinsonism is present in DLB, cannot be distinguished on clinical or pathological grounds. The conundrum exists for those DLB patients who do not yet have parkinsonism, and raises the parallel with patients who have Rapid Eye Movement Behavior Disorder but have not yet manifested parkinsonian signs. METHODS:A literature review was summarized to justify classification as a single disorder. RESULTS:Most clinical observations and trials point to these disorders, once parkinsonism is present in DLB, are identical. CONCLUSION:This article notes the advantage to clinical research and treatment by considering these two syndromes as the same so that medications approved for PDD and for PD psychosis can be extended to DLB patients and that resources for PD research and support can be also used for DLB.
10.1016/j.parkreldis.2017.07.013
The effectiveness of acupuncture for Parkinson's disease: An overview of systematic reviews.
Cao Liujiao,Li Xiuxia,Li Meixuan,Yao Liang,Hou Liangying,Zhang Weiyi,Wang Yongfeng,Niu Junqiang,Yang Kehu
Complementary therapies in medicine
OBJECTIVES:Acupuncture is an alternative therapy for Parkinson's disease (PD), but its efficacy and safety are controversial. This overview aimed to summarize the existing evidence from systematic reviews (SRs) and meta-analyses (MAs) in order to assess the effectiveness of acupuncture as a treatment for PD. METHODS:Seven electronic databases were searched from their inception until July 2019. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklists were used to assess evidence quality and methodological quality, respectively. The outcomes of study were calculated using mean differences (MDs) and risk ratios (RRs) with 95 % confidence intervals (CIs). A meta-analysis was performed using RevMan 5.3 software. RESULTS:A total of 12 SRs/MAs were included. All 12 SRs/MAs had more than one critical weakness in AMSTAR 2 and were considered of critically low methodological quality. The quality of evidence was unsatisfactory according to the GRADE checklist. Meta-analyses showed that acupuncture combined with drug for the treatment of PD can significantly improve the total effectiveness rate compared with drug alone (RR = 1.25, 95 % CI 1.16-1.34, P < 0.001). It was also found that acupuncture combined with drug significantly improved the UPDRS I-IV total summed scores (WMD=-6.18, 95 % CI -10.32 to -2.04, P < 0.001) and Webster scores (WMD=-4.20, 95 % CI -7.59 to -0.81, P < 0.001). CONCLUSION:Acupuncture might improve the UPDRS score, Webster score, and total effective rate in treatment of PD. It might be a safe and useful adjunctive treatment for patients with PD. However, we should interpret the findings of these reviews with caution, considering the overall limited methodological and reporting quality.
10.1016/j.ctim.2020.102383
[Disease-Modifying Therapy for Parkinson's Disease].
Shimura Hideki,Hattori Nobutaka
Brain and nerve = Shinkei kenkyu no shinpo
Currently, treatment of Parkinson's disease aims at alleviating its symptoms. However development of disease-modifying drugs has been a remarkable advancement in recent years. Furthermore, clinical trials of immunotherapy against α-synuclein, a protein involved in the pathogenesis of and lesion expansion in Parkinson's disease, have been initiated. Here, the disease-modifying treatment for patients with Parkinson's disease including the current α-synuclein immunotherapy, gene therapy, protein injection therapy, and cell transplantation therapy, has been reviewed.
10.11477/mf.1416200656
Self-management support programs for persons with Parkinson's disease: An integrative review.
Kessler Dorothy,Liddy Clare
Patient education and counseling
OBJECTIVE:To identify the characteristics of self-management programs for persons with Parkinson's disease and the evidence for their effectiveness. METHODS:An integrative literature review was conducted. Studies describing the provision or outcomes of self-management interventions for persons with Parkinson's disease and published in English were included. Two reviewers independently screened and evaluated articles. Interventions were described and compared, and evidence was presented using The Traffic Lighting system. RESULTS:Eighteen interventions were identified, representing a variety of group- and individual-based interventions that differed in structure, components, and outcomes. Notably, 89% were designed specifically for persons with Parkinson's disease and 39% combined self-management support with other therapies. Evidence to support specific self-management programs for persons with Parkinson's disease was limited. However, a moderate quality systematic review and a good quality RCT supported self-management for improving specific domains of quality of life. CONCLUSIONS:A variety of interventions have been designed to support self-management by persons with Parkinson's disease. More research is needed to identify key active ingredients and determine which programs are most effective. PRACTICE IMPLICATIONS:Self-management programs embedded within rehabilitation are promising. Clinicians should ensure programs include goal setting and problem solving and consider the inclusion of caregivers and peer support.
10.1016/j.pec.2017.04.011
Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions.
Translational neurodegeneration
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical description, PD remains a serious affliction that affects a growing proportion of the population. Prevailing treatments only alleviate symptoms; there is still neither a cure that targets the neurodegenerative processes nor therapies that modify the course of the disease. Over the past decades, several animal models have been developed to study PD. Although no model precisely recapitulates the pathology, they still provide valuable information that contributes to our understanding of the disease and the limitations of our treatment options. This review comprehensively summarizes the different animal models available for Parkinson's research, with a focus on those induced by drugs, neurotoxins, pesticides, genetic alterations, α-synuclein inoculation, and viral vector injections. We highlight their characteristics and ability to reproduce PD-like phenotypes. It is essential to realize that the strengths and weaknesses of each model and the induction technique at our disposal are determined by the research question being asked. Our review, therefore, seeks to better aid researchers by ensuring a concrete discernment of classical and novel animal models in PD research.
10.1186/s40035-023-00368-8
Neurobiology of placebo effect in Parkinson's disease: What we have learned and where we are going.
Quattrone Aldo,Barbagallo Gaetano,Cerasa Antonio,Stoessl A Jon
Movement disorders : official journal of the Movement Disorder Society
The placebo effect is a phenomenon produced when an inert substance administered like a regular treatment improves the clinical outcome. Parkinson's disease (PD) is one of the main clinical disorders for which the placebo response rates are high. The first evidence of the neurobiological mechanisms underlying the placebo effect in PD stems from 2001, when de la Fuente-Fernandez and colleagues demonstrated that a placebo injection led to the release of dopamine in the striatal nuclei of PD measured with positron emission tomography technology. Since then, several studies have been conducted to investigate the neurobiological underpinnings of placebo responses. This article presents a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Of an initial yield of 143 papers, 19 were included. The lessons learned from these studies are threefold: (i) motor improvement is dependent on the activation of the entire nigrostriatal pathway induced by dopamine release in the dorsal striatum; (ii) the magnitude of placebo-induced effects is modulated by an expectancy of improvement, which is in turn related to the release of dopamine within the ventral striatum; (iii) the functioning of the neural pathways underlying the placebo response can be tuned by prior exposure and learning strategies. In conclusion, although the neural network underlying the placebo effect in PD has been largely confirmed and accepted, what remains to be established is how, when, and where the expectation of reward (mediated by the ventral striatum) interacts with the primary motor system (mediated by the dorsal striatum) to induce clinical improvement in motor symptoms. © 2018 International Parkinson and Movement Disorder Society.
10.1002/mds.27438
[Anaesthesia and Parkinson's disease].
Chhor V,Karachi C,Bonnet A-M,Puybasset L,Lescot T
Annales francaises d'anesthesie et de reanimation
OBJECTIVE:The purpose of this review is to draw up a statement on current knowledge available on perioperative management of Parkinson's disease patients. STUDY DESIGN:Review. DATA SYNTHESIS:In France, approximately 150,000 persons suffer from Parkinson's disease, a neurodegenerative disorder of central nervous system. Parkinson's disease results in selective and irreversible loss of dopaminergic neurons in the substantia nigra pars compacta. Medications based on dopaminergic drugs are used to control motor symptoms and improve motor function. Development of surgical approach, especially deep brain stimulation, has revolutionized the medical management of many patients with Parkinson's disease. Anesthesia of these patients remains a challenge for the clinician. The aim of this review is to describe anaesthetic considerations of patients with Parkinson's disease and to discuss management of antiparkinsonians medications during the perioperative period.
10.1016/j.annfar.2011.02.012
The efficacy of imagery in the rehabilitation of people with Parkinson's disease: protocol for a systematic review and meta-analysis.
Systematic reviews
BACKGROUND:Parkinson's disease (PD) is a neurodegenerative disorder of the nervous system that affects movement. Individuals with PD commonly experience difficulty initiating movements, slowness of movements, decreased balance, and decreased standing ability. It has been shown that these motor symptoms adversely affect the independence of individuals with PD. Imagery is the cognitive process whereby a motor action is internally reproduced and repeated without overt physical movement. Recent studies support the use of imagery in improving rehabilitation outcomes in the PD population. However, these data have inconsistencies and have not yet been synthesised. The study will review the evidence on the use of imagery in individuals with PD and to determine its efficacy in improving rehabilitation outcomes. METHODS:Randomised controlled clinical trials comparing the effects of imagery and control on activities, body structure and function, and participation outcomes for people with PD will be included. A detailed computer-aided search of the literature will be performed from inception to June 2021 in the following databases: MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science, and Scopus. Two independent reviewers will screen articles for relevance and methodological validity. The Physiotherapy Evidence Database (PEDro) scale will be utilised to evaluate the risk of bias of selected studies. Data from included studies will be extracted by two independent reviewers through a customised, pre-set data extraction sheet. Studies using imagery with comparable outcome measures will be pooled for meta-analysis using the random effect model with 95% CI. If individual studies are heterogeneous, a descriptive review will analyse variance in interventions and outcomes. A narrative data analysis will be considered where there is insufficient data to perform a meta-analysis. DISCUSSION:Several studies investigating imagery in the PD population have drawn dissimilar conclusions regarding its effectiveness in rehabilitation outcomes and clinical applicability. Therefore, this systematic review will gather and critically appraise all relevant data, to generate a conclusion and recommendations to guide both clinical practice and future research on using imagery in the rehabilitation of people with PD. FUNDING:This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration number CRD42021230556.
10.1186/s13643-022-02041-z
Biomarkers for Parkinson's disease.
Graeber Manuel B
Experimental neurology
With the advent of systems biological concepts there has been a surge of interest in biological factors, or biomarkers that can be measured and which allow the identification of individuals at risk. Biomarkers for Parkinson's disease have been identified which provide evidence of systemic metabolic dysregulation in this disorder. Such biomarkers can be studied in blood, serum and plasma but also in CSF and urine, and the study by Hoepken et al. in this issue has even made use of skin fibroblasts. The authors report on the induction of alpha-synuclein expression and suggest that the expression changes described might potentially allow objective PD patient diagnosis in an accessible, peripheral tissue. This mini-review aims to provide a broader perspective on PD functional genomics and seeks to illustrate in a systems biological context why the findings by Hoepken and colleagues are of clinical significance.
10.1016/j.expneurol.2008.12.017
Executive dysfunction in Parkinson's disease: a review.
Dirnberger Georg,Jahanshahi Marjan
Journal of neuropsychology
Executive dysfunction can be present from the early stages of Parkinson's disease (PD). It is characterized by deficits in internal control of attention, set shifting, planning, inhibitory control, dual task performance, and on a range of decision-making and social cognition tasks. Treatment with dopaminergic medication has variable effects on executive deficits, improving some, leaving some unchanged, and worsening others. In this review, we start by defining the specific nature of executive dysfunction in PD and describe suitable neuropsychological tests. We then discuss how executive deficits relate to pathology in specific territories of the basal ganglia, consider the impact of dopaminergic treatment on executive function (EF) in this context, and review the changes in EFs with disease progression. In later sections, we summarize correlates of executive dysfunction in PD with motor performance (e.g., postural instability, freezing of gait) and a variety of psychiatric (e.g., depression, apathy) and other clinical symptoms, and finally discuss the implications of these for the patients' daily life.
10.1111/jnp.12028
Rheumatoid-like deformities in Parkinson's disease with 1-year follow-up: case report and literature review.
Shu Xiaoming,Wang Guochun,Lu Xin,Xie Yao
Rheumatology international
Rheumatoid-like deformities in joints are uncommon in patients with Parkinson's disease and easy to be misdiagnosed with rheumatoid arthritis. Therefore, unnecessary treatment is often initiated. Here, we report a case of a 60-year-old woman with Parkinson's disease developing a rheumatoid-like joint deformities, and evaluate 1-year follow-up outcome. We also review the literature and discuss the clinical characteristics, possible pathogenesis, and treatment strategy of these cases.
10.1007/s00296-009-1094-1
"Parkinson's disease" on the way to progressive supranuclear palsy: a review on PSP-parkinsonism.
Necpál Ján,Borsek Miroslav,Jeleňová Bibiána
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Progressive supranuclear palsy (PSP) is a progressive atypical parkinsonian syndrome characterised by postural instability, supranuclear ophthalmoplegia, dysarthria, dysphagia, executive dysfunction and other features. This clinical presentation represents the classic PSP-Richardson syndrome (PSP-RS). However, several other clinical subtypes have been recognised, including PSP-parkinsonism (PSP-P), probably the second most common PSP variant. Unlike PSP-RS, PSP-P often presents with an asymmetric onset, tremor and a moderate initial response to levodopa, especially during the first years of the disease, thus resembling Parkinson's disease (PD). It runs a more favourable course, but over time, PSP-P may evolve clinically into PSP-RS. Therefore, it may seem that PSP-P stands clinically between PD and PSP. There are several peculiarities that can distinguish PSP-P from these entities. As there is lack of systematic reviews on PSP-P in the literature, we decided to summarise all the necessary data about the epidemiology, clinical picture, neuroimaging, genetics and other aspects of this PSP variant in order to provide complete information for the reader.
10.1007/s10072-021-05601-8
The use of acupuncture in patients with Parkinson's disease.
Cheng Fung Kei
Geriatric nursing (New York, N.Y.)
Parkinson's disease, a progressive neuro-degeneration of multiple systems damaging motor and non-motor functions, affects individual and societal dimensions negatively. In addition to standard treatments, complementary and alternative medicine has been adopted, in which acupuncture, a traditional Chinese medical practice by needle penetration at specific stimulation points (acupoints) along the body, indicates positive outcomes in this illness. Apart from offering an overview of using acupuncture in Parkinson's disease, this literature review analyses the effects of acupuncture on Parkinson's-induced physical symptoms and mental problems such as slow movements, stiffness, constipation, and sleep disorders. In light of the 35 reviewed research projects in mainland China, Japan, Korea, Taiwan, and the United States of America, this study reveals the optimization of this approach through combined therapy and its preventive contribution using acupuncture alone. It also suggests research and practical implications that hint at enhancements in medical applications.
10.1016/j.gerinurse.2016.11.010
Unmet needs in Parkinson's disease: New horizons in a changing landscape.
Chaudhuri K Ray,Bhidayasiri Roongroj,van Laar Teus
Parkinsonism & related disorders
The success of levodopa and other classes of drugs have meant that most people with Parkinson's disease enjoy a good quality of life for many years. However, despite the availability of several drugs and formulations that can be used as monotherapy and in combination, there are a number of disease features that the current therapies are unable to address. The disease continues to progress despite treatment, patients suffer from a myriad of motor and non-motor symptoms, and a neuroprotective therapy is urgently required. To move forward with medical and surgical management, it is important to consider new insights that recent research offers and in this review we examine how a better understanding of the disease pathology and progression might improve and enrich our daily clinical practice. It is also timely to consider the service provision changes that will increasingly be needed to effectively manage the needs of the aging population.
10.1016/j.parkreldis.2016.11.018
Total knee arthroplasty in patients with Parkinson's disease: A systematic review and meta-analysis protocol.
Medicine
BACKGROUND:Parkinson's disease (PD) patients have been shown to have various musculoskeletal problems, the postoperative outcomes of total knee arthroplasty procedure might be less predictable if performed on a patient who has PD. We conducted a protocol for systematic review and meta-analysis to evaluate the functional outcomes, activity levels, mortalities, implant survival rates, and complications of total knee arthroplasty in patients with PD. METHODS:This study follows the guideline of the preferred reporting items for systematic reviews and meta-analyses protocols and has been registered on the International Prospective Register of Systematic Reviews with CRD42022375885. Two independent reviewers will search for databases including PubMed, Embase, Cochrane Library website, ClinicalTrials.gov databases, Chinese National Knowledge Infrastructure Database, Wanfang database, and VIP database using the search strategies recommended by the Cochrane Back Review Group. The RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) will be used to conduct the meta-analyses. RESULTS:The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION:This study may provide evidence for the clinical application of total knee arthroplasty in patients with PD.
10.1097/MD.0000000000032315
Parkinson's disease in Africa: A systematic review of epidemiologic and genetic studies.
Okubadejo Njideka U,Bower James H,Rocca Walter A,Maraganore Demetrius M
Movement disorders : official journal of the Movement Disorder Society
Parkinson's disease (PD) occurs worldwide, but little is known about PD in Africa. We systematically reviewed publications on PD in Africa, with emphasis on epidemiologic and genetic studies. Articles published between 1944 and December 2004 were identified using several strategies. The studies emanated from 13 African countries (Kenya, Uganda, Tanzania, Ethiopia, Nigeria, Senegal, Ghana, Togo, Libya, Tunisia, Algeria, Zimbabwe, and South Africa). The publications fell into four categories: clinical series (n = 17), prevalence studies (n = 7), incidence studies (n = 1), and genetic studies (n = 3). The clinical series documented the occurrence of PD in Africa and described its clinical characteristics. The prevalence studies suggested some intracontinental geographic variation in PD prevalence. Overall, the prevalence figures and the incidence rates of PD in Africa appeared lower than those reported for European and North American populations. Few genetic studies of PD have been reported from Africa, and none in blacks. There are no case-control or cohort studies of PD reported from Africa. This review provides a summary of PD research in Africa over the past 60 years and highlights the information gaps and potential areas for future research.
10.1002/mds.21153
A Guideline for Parkinson's Disease Nurse Specialists, with Recommendations for Clinical Practice.
Lennaerts Herma,Groot Marieke,Rood Berna,Gilissen Koen,Tulp Hella,van Wensen Erik,Munneke Marten,van Laar Teus,Bloem Bastiaan R
Journal of Parkinson's disease
BACKGROUND:Parkinson's Disease Nurse Specialists (PDNS) play an important role in the care for patients with Parkinson's disease (PD) and their caregivers. Until now, there were no nursing guidelines in PD, and interventions were based solely on daily clinical practice because there is no evidence to support the merits of nursing interventions. Consequently, there is little uniformity in current care delivery. OBJECTIVE:Developing a guideline for PDNS. METHODS:We developed a guideline based on a questionnaire among PDNS and a literature review, supplemented with expert opinion plus the input of patients and caregivers. The questionnaire was filled in by 97 PDNS and 51 generic nurses with knowledge of PD to identify barriers in PD nursing care. Subsequently, we did a systematic literature search and transformed these sources of information into practice recommendations, which were developed according to international standards for guideline development. RESULTS:Based on the results of the questionnaire we identified seven specific core areas: defining the role of PDNS in terms of caseload, education, competences and care coordination; medication adherence; provision of information and education; coping; caregiver support; urogenital function and orthostatic hypotension. The systematic literature search identified 186 studies, of which 33 studies were finally analyzed. Furthermore, we developed practice recommendations based on good clinical practice for the following areas: self-care, mental functioning, mobility, nutrition, sexuality, work, sleep, palliative care and complementary (integrative) care. CONCLUSION:This guideline provide ground to harmonize care delivery by PDNS in clinical practice, and offer a foundation for future research.
10.3233/JPD-171195
Computerised cognitive training in Parkinson's disease: a protocol for a systematic review and updated meta-analysis.
Gavelin Hanna Malmberg,Domellöf Magdalena,Leung Isabella,Neely Anna Stigsdotter,Finke Carsten,Lampit Amit
BMJ open
INTRODUCTION:Cognitive impairment is recognised as an important non-motor symptom in Parkinson's disease (PD) and there is a need for evidence-based non-pharmacological interventions that may prevent or slow cognitive decline in this patient group. One such intervention is computerised cognitive training (CCT), which has shown efficacious for cognition across older adult populations. This systematic review aims to investigate the efficacy of CCT across cognitive, psychosocial and functional domains for people with PD and examine study and intervention design factors that could moderate CCT effects on cognition. METHODS AND ANALYSIS:Randomised controlled trials investigating the effects of CCT in patients with PD without dementia, on cognitive, psychosocial or functional outcomes, will be included. The primary outcome is overall cognitive function. Secondary outcomes are domain-specific cognitive function, psychosocial functioning and functional abilities. We systematically searched MEDLINE, Embase and PsycINFO through 14 May 2020 to identify relevant literature. Risk of bias will be assessed using the revised Cochrane Risk of Bias tool. Effect sizes will be calculated as standardised mean difference of baseline to postintervention change (Hedges' ) with 95% CI for each eligible outcome measure. Pooling of outcomes across studies will be conducted using random-effects models, accounting for dependency structure of effect sizes within studies. Heterogeneity will be assessed using τ and I statistic. Potential moderators, based on key study and intervention design factors, will be investigated using mixed-effects meta-regression models. ETHICS AND DISSEMINATION:No ethical approval is required. The findings will be disseminated in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER:CRD42020185386.
10.1136/bmjopen-2020-040656
Efficacy and safety of abdominal acupuncture in Parkinson's disease: A protocol for systematic review and meta-analysis.
Medicine
BACKGROUND:Parkinson disease (PD) is a worldwide spread neurodegenerative disorder. Dopamine replacement therapy is currently the mainstream treatment, which can alleviate the symptoms but induces motor complications. Acupuncture therapy is effective for PD. As a form of acupuncture, the abdominal acupuncture has been used to relieve symptoms in patients with PD, but its effectiveness and safety have not yet reached a definitive conclusion. Therefore, this systematic review and meta-analysis protocol is planned to evaluate the efficacy and safety of abdominal acupuncture for PD patients. METHODS:Six English databases (PubMed, Web of Science, MEDLINE, EMBASE, Springer Cochrane Library, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wan Fang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to August 20, 2022. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Any disagreement will be resolved by discussion with the third reviewer. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. The analysis will be conducted by RevMan 5.3 software according to Cochrane Handbook. RESULTS:The aim of this systematic review is to provide high-quality evidence to assess the efficacy and safety of abdominal acupuncture for patients in Parkinson's disease. The efficacy and safety of abdominal acupuncture for PD will be comprehensively assessed from the outcomes, including the effectiveness rate. The Unified Parkinson Disease Rating Scale (UPDRS) and Webster scale, Motor symptom scores utilizing UPDRS III scale, Dopamine (DA) content, and Nonmotor symptom scores employing UPDRS I scale, Activities of daily living using UDPRS II; Complications of treatment applying UPDRS IV, antioxidant ability: super oxide dismutase activity and Lipide Peroxide (LPO) content, Content of inflammatory cytokines, tumor necrosis factor-α and interleukin-1β, and adverse events as the secondary outcome. CONCLUSION:This systematic review will explore whether abdominal acupuncture is an effective and safe intervention for patients in Parkinson's disease.
10.1097/MD.0000000000031804
Treatment of early Parkinson's disease.
Pahwa Rajesh,Lyons Kelly E
Current opinion in neurology
PURPOSE OF REVIEW:This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. RECENT FINDINGS:The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. SUMMARY:Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.
10.1097/WCO.0000000000000113
Role of homocysteine in the development and progression of Parkinson's disease.
Annals of clinical and translational neurology
Homocysteine is an essential intermediate product of biochemical reactions that is present in various tissues of the human body. Homocysteine may be associated with the development and progression of Parkinson's disease. Plasma homocysteine levels in patients with Parkinson's disease are elevated compared to those of healthy individuals. High homocysteine drives PD development and progression while aggregating the clinical symptoms of PD patients. The relationship between PD and homocysteine involves multiple pathways, including nerve cell apoptosis, oxidative stress, and DNA damage. This is crucial for explaining how high homocysteine drives the PD procession. Elevated homocysteine level during PD development and progression offers a new strategy for the diagnosis and treatment of this disease.
10.1002/acn3.51227
New concepts in the pathogenesis and presentation of Parkinson's disease.
Clinical medicine (London, England)
Parkinson's disease (PD) was first described by James Parkinson in 1817. He noted the complex nature of this condition and that non-motor symptoms (NMS) underpinned the classic motor symptoms of PD. The concept of what PD is has therefore undergone substantial changes and it is now recognised that PD is a combined motor and non-motor syndrome and NMS are present during the prodromal phase of PD, starting up to 20 years before the first clinical motor signs emerge. PD may originate from pathology in the gut, olfactory bulb and lower brainstem rather than in the substantia nigra. Complex phenotypes of PD may exist where clinical NMS overshadow motor features. Therapy needs to be adjusted based on motor and non-motor loads, ideally using validated tools. Recently, a multimodal biomarker battery in PD has emerged and might play an important role in the future.
10.7861/clinmedicine.16-4-365
Fatigue in Parkinson's disease.
Friedman Joseph H,Abrantes Ana,Sweet Lawrence H
Expert opinion on pharmacotherapy
INTRODUCTION:Non-motor symptoms of Parkinson's disease (PD) have become increasingly recognized as central to the disease. These include somatic symptoms, such as pain and autonomic dysfunction (bladder dysfunction, constipation, dipahoresis and orthostatic hypotension) and behavioral problems, such as dementia, depression, fatigue, sleep disorders and psychosis. Research on fatigue has focused on its epidemiology with only a single report of a beneficial treatment trial, which used methylphenidate. AREAS COVERED:This review was made of all articles related to fatigue in Parkinson's disease arising in PUBMED. It will cover the types of fatigue, epidemiology, pathophysiology and treatment of fatigue in PD. EXPERT OPINION:Fatigue is a common and severe problem in Parkinson's disease. Virtually nothing is known about it aside from its epidemiology. It is an area greatly in need of investigation.
10.1517/14656566.2011.587120
Recognition and treatment of autonomic disturbances in Parkinson's disease.
Li Kai,Reichmann Heinz,Ziemssen Tjalf
Expert review of neurotherapeutics
Symptoms of dysautonomia are common in Parkinson's disease (PD), and almost all the functional autonomic subsystems can be involved in PD. However, they are still under-recognized in everyday clinical practice. Autonomic dysfunction can be observed in the early stages of PD, affect a substantial proportion of patients, impact quality of life and can also help in differential diagnosis. This review aims to provide an overview of the pathophysiology, clinical manifestations, relevant examination and treatment of cardiovascular, gastrointestinal, urogenital, thermoregulatory and pupil autonomic dysfunctions in Parkinson's disease.
10.1586/14737175.2015.1095093
Working capacity of patients with Parkinson's disease - A systematic review.
Koerts Janneke,König Miriam,Tucha Lara,Tucha Oliver
Parkinsonism & related disorders
INTRODUCTION:Parkinson's disease (PD) is characterized by motor and non-motor symptoms and has a median age-of-onset around 55 years. Many PD patients are thus diagnosed before reaching retirement age and it is likely that they are confronted with a reduced working capacity or loss of employment. This systematic literature review gives an overview of the research conducted on work capacity in PD. METHODS:A systematic literature search was performed in PsycINFO and PubMed (Keywords: "Parkinson" or "Parkinson's disease" combined with "employment", "work", "working", "retire" or "retirement"). RESULTS:Thirteen studies were identified and showed that PD patients retired 4-7 years earlier than the general population. Furthermore, 23%-75% of patients report that they retired early because of PD and slowness and fatigue were reported as the most debilitating symptoms in relation to working capacity. Early retirement of PD patients is associated with high societal costs and a high loss of individual lifetime earnings. Although many employed PD patients asked for adjustments at their workplace, their employers did not always support these. CONCLUSIONS:PD has a detrimental effect on working capacity and is associated with high costs. Employed PD patients do not, however, always receive the support they need. It is therefore very relevant that employers and patients are informed about strategies and techniques developed for counteracting symptoms of PD which might support patients to stay in the workforce for a longer period of time.
10.1016/j.parkreldis.2016.03.017
Extrinsic and Behavioral Fall Risk Factors in People With Parkinson's Disease: An Integrative Review.
Kuljeerung Orawan,Lach Helen W
Rehabilitation nursing : the official journal of the Association of Rehabilitation Nurses
AIM:The aim of the study was to explore extrinsic and behavioral risks for falls in older adults with Parkinson's disease (PD). BACKGROUND:Falls that cause injury and disability in people with PD are common. Understanding the role of extrinsic and behavioral factors is important for fall prevention. DESIGN:Integrative literature review with search of CINAHL, MEDLINE, and SCOPUS and ancestry searching was performed. METHODS:The methodology of Whittemore and Knafl guided the review; ten studies were included. FINDINGS:Falls occur indoors and outdoors, commonly during daily activities in familiar home environments, but also when out in the community. Common challenges include uneven and unfamiliar environments and risky behavior like hurrying. CONCLUSION:Extrinsic risk factors combined with behavioral and intrinsic factors contribute to falls in people with PD both at home and in the community. CLINICAL RELEVANCE:Rehabilitation of people with PD should include assessment of falls, function, extrinsic risk factors, and fit with their environment to develop fall prevention plans.
10.1097/rnj.0000000000000265
Imaging Systemic Dysfunction in Parkinson's Disease.
Borghammer Per,Knudsen Karoline,Brooks David J
Current neurology and neuroscience reports
Parkinson's disease is now widely recognized to be a multisystem disorder affecting the brain and peripheral autonomic nerves. Extensive pathology is present in both the sympathetic and parasympathetic nervous system and the intrinsic gastrointestinal plexuses in patients. Autonomic pathology and symptoms such as constipation can predate the clinical diagnosis by years or decades. Imaging studies have contributed greatly to our understanding of Parkinson's disease but focused primarily on imaging cerebral pathology. However, given the importance of understanding the nature, chronology, and functional consequences of peripheral pathology, there has been renewed interest in imaging peripheral organs in Parkinson's disease. Suitable imaging tools can be divided into two types: radiotracer studies that directly estimate loss of sympathetic or parasympathetic nerve terminals, and imaging modalities to quantitate dysphagia, gastric emptying, esophageal and intestinal transit times, and anorectal dyssynergia. In this review, we summarize current knowledge about peripheral imaging in Parkinson's disease.
10.1007/s11910-016-0655-4
Subtypes of Parkinson's disease: state of the field and future directions.
Marras Connie
Current opinion in neurology
PURPOSE OF REVIEW:Previously, outstanding questions have been identified including the relationship of proposed subtypes to etiology, underlying biology, and prognosis. This situation presents an opportunity for major developments in the field. The review summarizes the progress made over the past 1-2 years. RECENT FINDINGS:The etiologic, physiological, and clinical differences between tremor dominant, postural instability gait disorder, and indeterminate phenotypes have been further explored, finding genetic influences, functional imaging and clinical differences. New cluster analyses suggest that nonmotor features are important aspects of Parkinson's disease subtypes, but there was little association found between tremor-dominant /postural instability gait disorder phenotype and nonmotor symptoms. In the cognitive realm, empirically derived subtypes of PD-MCI did not map well onto cognitive subtypes derived using a data-driven approach. In data-driven subtype research, important survival differences between subtypes were identified within the PROPARK database. SUMMARY:It will be important to revisit PD-MCI classification to consider subtyping based upon data that relate cognitive phenotype to prognosis. Given the traction that traditional motor subtyping has had in the field it would be of value to consider how nonmotor symptom clusters can be used with or alongside the motor subtypes. Finally, incorporating subtypes into clinical trials remains a significant gap in Parkinson's disease research.
10.1097/WCO.0000000000000219
Available and emerging treatments for Parkinson's disease: a review.
Drug design, development and therapy
Parkinson's disease is a commonly encountered neurodegenerative disorder primarily found in aged populations. A number of medications are available to control symptoms, although these are less effective in advanced disease. Deep brain stimulation provides a practicable alternative at this stage, although a minority of patients meet the strict criteria for surgery. Novel medications that provide enhanced symptomatic control remain in developmental demand. Both gene and cell-based therapies have shown promise in early clinical studies. A major unmet need is a treatment that slows or stops disease progression.
10.2147/DDDT.S11836
Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.
Journal of neural transmission (Vienna, Austria : 1996)
Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.
10.1007/s00702-017-1799-3
Vocal tract characteristics in Parkinson's disease.
Gillivan-Murphy Patricia,Carding Paul,Miller Nick
Current opinion in otolaryngology & head and neck surgery
PURPOSE OF REVIEW:Voice tremor is strongly linked to the Parkinson's disease speech-voice symptom complex. Little is known about the underlying anatomic source(s) of voice tremor when it occurs. We review recent literature addressing this issue. Additionally we report findings from a study we conducted employing rating of vocal tract structures viewed using nasolaryngoscopy during vocal and nonspeech tasks. RECENT FINDINGS:In Parkinson's disease, using laryngeal electromyography, tremor has not been identified in muscles in the vocal folds even when perceived auditorily. Preliminary findings using nasolaryngoscopy suggest that Parkinson's disease voice tremor is not associated with the vocal folds and may involve the palate, the global larynx, and the arytenoids. Tremor in the vertical larynx on /a/, and tremor in the arytenoid cartilages on /s/ differentiated patients with Parkinson's disease from neurologically healthy controls. Visual reliable detection of tremor when it is absent or borderline present, is challenging. SUMMARY:Parkinson's disease voice tremor is likely to be related to oscillatory movement in structures across the vocal tract rather than just the vocal folds. To progress clinical practice, more refined tools for the visual rating of tremor would be beneficial. How far voice tremor represents a functionally significant factor for speakers would also add to the literature.
10.1097/MOO.0000000000000252
The Relationship Between Anxiety Disorders and Parkinson's Disease: Clinical and Therapeutic Issues.
Abou Kassm Sandra,Naja Wadih,Haddad Ramzi,Pelissolo Antoine
Current psychiatry reports
PURPOSE OF REVIEW:This paper seeks to describe anxiety's different symptomatologic presentations in Parkinson's disease (PD), its longitudinal course and predictors, as well as its motor and non-motor correlates. It also reviews the available screening tools and different treatment modalities. RECENT FINDINGS:In PD, longitudinal predictors of anxiety are mostly non-motor non-dopaminergic symptoms. The longitudinal course of anxiety is mainly a stable one. The Parkinson Anxiety Scale and the Geriatric Anxiety Scale are the 2 recommended screening tools. A third of PD patients suffer from an anxiety disorder at any time point. It can precede or follow PD motor symptoms. Anxiety is associated with demographic, disease-related motor and non-motor features. There is a lack of studies evaluating psychotropic treatment of anxiety in PD. Adjustment of dopaminergic treatment is indicated when anxiety is associated with motor fluctuations. DBS can be useful as well as CBT and body-mind interventions.
10.1007/s11920-021-01229-9
Dementia in Parkinson's disease.
Robottom Bradley J,Weiner William J
International review of neurobiology
Parkinson's disease is the second most common neurodegenerative illness diagnosed in the United States. Dementia is recognized as a common component of advanced Parkinson's disease (PD). In patients with early PD, cognitive changes occur and primarily reflect impairment in executive function. It is unknown if the early cognitive changes detected on neuropsychological testing in Parkinson's disease are predictive of the subsequent development of Parkinson's disease with dementia (PDD). Many patients with PD develop dementia characterized by a wide range of cognitive deficits distinct from those seen in Alzheimer's disease (AD). Neuropsychiatric problems frequently accompany PDD. This chapter reviews the epidemiology, clinical characteristics of early and late cognitive changes, pathology, neuroimaging, diagnosis, and treatment of PDD.
10.1016/S0074-7742(09)00412-7
PET Molecular Imaging in Familial Parkinson's Disease.
Matarazzo Michele,Wile Daryl,Mackenzie Melissa,Stoessl A Jon
International review of neurobiology
Most cases of Parkinson's disease (PD) are idiopathic, but some characteristics, such as early onset or a positive family history, raise suspicions of an inherited form of the disease. In the last decades several genes have been linked to parkinsonism, with different patterns of inheritance and different clinical phenotypes. Positron emission tomography (PET) imaging has helped to characterize genetic-linked parkinsonism, thanks to the availability of dopaminergic and nondopaminergic tracers. On the other hand, investigation of molecular changes in mutation carriers, even at preclinical stages, has provided a deeper comprehension of the pathogenesis of PD and of the compensatory mechanisms that take place in the very early stages of the disease.
10.1016/bs.irn.2018.09.003
The effects of exercise on cognition and gait in Parkinson's disease: A scoping review.
Neuroscience and biobehavioral reviews
Cognitive and gait deficits are two debilitating symptoms that occur in Parkinson's disease (PD). Importantly, a relationship between cognitive and gait deficits exists in PD, suggesting reliance on cognition is increased to compensate for gait deficits and/or deterioration of cognition and gait may share common mechanisms. Rehabilitation strategies targeting one factor could lead to the improvement of the other, presenting a unique opportunity to treat both simultaneously. Gold-standard pharmaceuticals partially alleviate these deficits with significant side effects, highlighting the importance of investigating adjunct therapies like exercise. We critically reviewed the influence of three exercise modalities (aerobic, resistance, and goal-based) on cognition and/or gait in PD. Most studies showed improvements in cognition or gait, yet, a limited number investigated them concurrently. This is the first review examining exercise for cognition and gait in PD. Key gaps in the literature are identified; potential exercise-driven mechanisms for enhancements in cognition and gait proposed, and suggestions for the design of future studies investigating the effects of exercise on cognition and gait in PD.
10.1016/j.neubiorev.2018.09.018
Copper and copper proteins in Parkinson's disease.
Montes Sergio,Rivera-Mancia Susana,Diaz-Ruiz Araceli,Tristan-Lopez Luis,Rios Camilo
Oxidative medicine and cellular longevity
Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.
10.1155/2014/147251
The Role of Parkinson Nurses for Personalizing Care in Parkinson's Disease: A Systematic Review and Meta-Analysis.
Journal of Parkinson's disease
BACKGROUND:Quality of life (QoL) of persons with Parkinson's disease (PD) is diminished by (non-)motor symptoms, that require personalized care. Parkinson Nurses (PN) may be pivotal promoting tailored care offerings. This systematic review and meta-analysis investigates PD care models and aims at furnishing current concepts of PN to offer personalized care. OBJECTIVE:The purpose of this study is to identify the various roles and functions that PN may hold for personalized PD care. METHODS:We performed a systematic literature review, utilizing: PubMed, Web of Science, The Cochrane Library, and PsycINFO. The review qualitatively evaluated articles, which described personalized care models involving PNs and was guided by the personalized care management model. A meta-analysis compared patient-reported QoL (quantified using the 39-item Parkinson's Disease Questionnaire) between personalized care interventions involving PN versus standard care with. RESULTS:Twenty-seven publications were identified, including six randomized, controlled trials ascertaining with health related QoL (n = 1830 PwPs). The qualitative evaluation revealed that PN contribute to all aspects of personalized care. The meta-analysis showed no improved QoL in personalized care models compared to standard care, thought a great heterogeneity among study design and interventions was outlined (Standardized Mean Difference = -0.8935; 95% Confidence Interval, -2.1177 to 0.3307; z = -1.43, p = 0.1526). CONCLUSION:PN fulfil important functions in personalized PD care. For the future, a clear role definition will be necessary to adjust training for PN across healthcare systems and care settings but especially to realize their full potential for PD care.
10.3233/JPD-223215
Biomarkers in Parkinson's disease.
Morgan John C,Mehta Shyamal H,Sethi Kapil D
Current neurology and neuroscience reports
Biomarkers are objectively measured characteristics that are indicators of normal biological processes, pathogenic processes, or responses to therapeutic interventions. To date, clinical assessment remains the gold standard in the diagnosis of Parkinson's disease (PD) and clinical rating scales are well established as the gold standard for tracking progression of PD. Researchers have identified numerous potential biomarkers that may aid in the differential diagnosis of PD and/or tracking disease progression. Clinical, genetic, blood and cerebrospinal fluid (proteomics, transcriptomics, metabolomics), and neuroimaging biomarkers may provide useful tools in the diagnosis of PD and in measuring disease progression and response to therapies. Some potential biomarkers are inexpensive and do not require much technical expertise, whereas others are expensive or require specialized equipment and technical skills. Many potential biomarkers in PD show great promise; however, they need to be assessed for their sensitivity and specificity over time in large and varied samples of patients with and without PD.
10.1007/s11910-010-0144-0
Bilirubin: A Promising Therapy for Parkinson's Disease.
International journal of molecular sciences
Following the increase in life expectancy, the prevalence of Parkinson's disease (PD) as the most common movement disorder is expected to rise. Despite the incredibly huge efforts in research to find the definitive biomarker, to date, the diagnosis of PD still relies mainly upon clinical symptoms. A wide range of treatments is available for PD, mainly alleviating the clinical symptoms. However, none of these current therapies can stop or even slow down the disease evolution. Hence, disease-modifying treatment is still a paramount unmet medical need. On the other side, bilirubin and its enzymatic machinery and precursors have offered potential benefits by targeting multiple mechanisms in chronic diseases, including PD. Nevertheless, only limited discussions are available in the context of neurological conditions, particularly in PD. Therefore, in this review, we profoundly discuss this topic to understand bilirubin's therapeutical potential in PD.
10.3390/ijms22126223
Psychosis in Parkinson's disease: From the soft signs to the hard science.
Lenka Abhishek,Herath Priyantha,Christopher Rita,Pal Pramod Kumar
Journal of the neurological sciences
Patients with Parkinson's disease (PD) may develop a wide spectrum of non-motor symptoms during the course of illness. Psychosis is one such commonly observed non-motor symptoms of PD. Although several studies based on neuroimaging, genetics, retinal imaging, and neuropsychological evaluations have explored the pathogenesis of psychosis in PD; exact neural correlates are yet to be understood. Identification of factors related to psychosis in PD is important, as psychosis has been reported to be associated with higher rates of mortality, caregiver distress, and nursing home placements. This review highlights the potential of the previous studies to gain further insights into the soft signs and hard science related to psychosis in PD. Studies based on neuropsychological evaluations have revealed significant dysfunction in attention, executive and visuospatial functions in patients with PD and psychosis. Neuroimaging studies reveal grey matter atrophy in regions of the brain corresponding to both dorsal and ventral visual pathways, hippocampus, and cholinergic structures. Meanwhile, functional imaging studies suggest existence of an aberrant top-to-bottom visual processing system, which dominates the normal bottom-to-top system in patients with PD and visual hallucinations. Although nucleotide polymorphisms of several genes have been studied in PD patients with psychosis, those on -45C>T polymorphisms of cholecystokinin gene (CCK) have shown the greatest promise because of its association with psychosis in PD. All these taken together, cohesively unfold the current status of research in patients with PD and psychosis. This paper also highlights the missing links and discusses the approach to future research in this field.
10.1016/j.jns.2017.06.011
Functional MRI in Parkinson's Disease Cognitive Impairment.
Baggio Hugo C,Junqué Carme
International review of neurobiology
Functional magnetic resonance imaging (fMRI) has been used to study the neural bases of cognitive deficits in Parkinson's disease for several years. Traditionally, task-based fMRI has been applied to study specific cognitive functions, providing information on disease-related alterations and regarding the physiological bases of normal cognition, the dopaminergic system, and the frontostriatal circuits. More recently, functional connectivity techniques using resting-state fMRI data have been developed. Unconstrained by specific cognitive tasks, these techniques allow assessing whole-brain patterns of connectivity believed to be useful proxies for the underlying functional architecture of the brain. These methods have shown that different types of Parkinson's disease-related cognitive deficits are associated with patterns of altered connectivity within and between resting-state intrinsic connectivity networks. Although methodological standardization and the vulnerability of fMRI techniques to artifacts mandate further technical refinement, early studies provide encouraging results regarding the potential of fMRI-derived parameters for the ultimate goal of individual-subject classification.
10.1016/bs.irn.2018.09.010
THE ROLE OF CIRCADIAN REGULATION OF GHRELIN LEVELS IN PARKINSON'S DISEASE (LITERATURE REVIEW).
Wiadomosci lekarskie (Warsaw, Poland : 1960)
The paper is aimed at the analysis of the role of the circadian regulation of ghrelin levels in patients with Parkinson's disease. Based on the literature data, patients with Parkinson's disease have clinical fluctuations in the symptoms of the disease, manifested by the diurnal changes in motor activity, autonomic functions, sleep-wake cycle, visual function, and the efficacy of dopaminergic therapy. Biological rhythms are controlled by central and peripheral oscillators which links with dopaminergic neurotransmission - core of the pathogenesis of Parkinson`s disease. Circadian system is altered in Parkinson`s disease due to that ghrelin fluctuations may be changed. Ghrelin is potential food-entrainable oscillator because it is linked with clock genes expression. In Parkinson`s disease this hormone may induce eating behavior changing and as a result metabolic disorder. The "hunger hormone" ghrelin can be a biomarker of the Parkinson's disease, and the study of its role in the pathogenesis, as well as its dependence on the period of the day, intake of levodopa medications to improve the effectiveness of treatment is promising.
Peripheral neuropathy in idiopathic Parkinson's disease: A systematic review.
Zis Panagiotis,Grünewald Richard A,Chaudhuri Ray Kallol,Hadjivassiliou Marios
Journal of the neurological sciences
BACKGROUND:Parkinson's disease (PD) has been associated with peripheral neuropathy (PN). PN has been demonstrated in some rare genetic forms of PD (e.g. PARK2 mutations) but has also been linked to levodopa exposure. OBJECTIVE:The aim of this systematic review is to clarify any evidence of peripheral nervous system involvement in idiopathic PD. METHODS:A systematic computer-based literature search was conducted on PubMed database. FINDINGS:The pooled estimate of the prevalence of large fiber PN in PD was 16.3% (based on 1376 patients). The pooled estimate of the prevalence of biopsy-proven small fiber neuropathy was 56.9% (based on 72 patients). Large fiber PN in PD is in the majority of cases distal, symmetrical, axonal and predominantly sensory. There are, however, few reports of chronic idiopathic demyelinating polyneuropathy and very occasional cases of acute neuropathies. Although nerve conduction studies have been performed in the majority of the studies, they included only a limited number of nerves, mainly in the lower limbs. There is little evidence to support a direct link between levodopa treatment and the development of PN in idiopathic PD. In the majority of the cases PN has been linked to abnormalities in vitamin B12, methylmalonic acid or fasting homocysteine levels. Additional aetiological risk factors for PN may be responsible for any apparent link between PD and PN. CONCLUSIONS:Large-scale prospective studies with long-term follow-up with detailed baseline assessments are needed in order to understand the natural history of PN in PD, both on clinical and neurophysiological parameters.
10.1016/j.jns.2017.05.023
Physical exercise and its effects on people with Parkinson's disease: Umbrella review.
PloS one
INTRODUCTION:Parkinson's disease is neurodegenerative, complex and progressive, manifesting in a slow and irreversible way. Physical exercise has been proposed as therapeutic alternative to people with Parkinson´s disease. OBJECTIVE:To synthesize knowledge about the effects of physical exercise on people with Parkinson´s Disease as presented by published systematic reviews. METHODS:Nine electronic databases and two grey literature databases were searched for systematic reviews reporting the effects of physical exercises on people with Parkinson´s Disease. Searches involved a two-phase process, by, at least, two independent reviewers. Methodological quality of the included systematic reviews was assessed using AMSTAR-2. RESULTS:From 2,122 systematic reviews, 139 were included. Motor outcomes were assessed in 91% of the studies, with balance being the most studied. Non-motor outcomes were assessed in 68% of the studies, with emphasis on quality of life. Physical exercises were classified into five categories: aerobic exercises, strength, combined, sensorimotor activities and other activity protocols. Findings of the systematic reviews suggest that all exercise categories can be prescribed to improve balance and mobility, while combined exercises, strength, and specific activities improve both motor and non-motor outcomes, and aerobic exercise and sensorimotor activities improve motor outcomes. CONCLUSION:Current evidence from systematic reviews suggests that physical exercises impacts both motor and non-motor outcomes in people with Parkinson´s Disease. Limits in evidence provided by the systematic reviews were related to methodological issues and to the description of the interventions and must be considered to improve decision-making and clinical application.
10.1371/journal.pone.0293826
Parkinson's disease in the older patient.
Clinical medicine (London, England)
Parkinson's disease (PD) is the second most commonly encountered neurodegenerative condition in clinical practice and probably offers a significantly greater variety of challenges than the management of Alzheimer's disease. As with most neurodegenerative diseases, age represents the leading risk factor for the development of PD. Current estimates would suggest that PD affects 1-2% of people over the age of 65 years and each decade sees an increasing number of cases. In addition, it is well recognised that most industrialised nations have an increasing proportion of individuals living longer. For example, recent data from Australia indicates that the prevalence of PD is anticipated to rise by 80% over the next 20 years and as such, we must all strive towards improving our clinical management of this common condition. In this article, we will attempt to highlight the issues that should be actively sought out and, where possible, addressed. We hope that an improved level of understanding will lead to better outcomes in older patients with PD.
10.7861/clinmedicine.16-4-376
Sensory symptoms in Parkinson's disease: Clinical features, pathophysiology, and treatment.
Zhu Mingxin,Li Man,Ye Dawei,Jiang Wei,Lei Ting,Shu Kai
Journal of neuroscience research
Parkinson's disease (PD) is one of the most common forms of neurodegenerative disease in the elderly population and is typically manifested by motor symptoms and nonmotor symptoms and signs. Nonmotor symptoms, such as sensory symptoms, have been regarded as the significant features of this disease. These symptoms often occur in early stages of PD and influence quality of life. However, researchers suggest that the sensory symptoms of PD are frequently unrecognized by clinicians and remain untreated. The disorders include pain, olfactory disturbance, and visual dysfunction input on the underlying sensory abnormality. This Review focuses on the clinical features, pathophysiological mechanisms, and treatment strategies for sensory symptoms of PD from both clinical studies and basic research, providing a comprehensive overview of the sensory symptoms in PD. © 2016 Wiley Periodicals, Inc.
10.1002/jnr.23729
The Gastrointestinal Dysfunction Scale for Parkinson's Disease.
Camacho Marta,Greenland Julia C,Williams-Gray Caroline H
Movement disorders : official journal of the Movement Disorder Society
BACKGROUND:Gastrointestinal dysfunction is an important feature of Parkinson's disease (PD), and there is increasing evidence that it may play a key role in the disease process. However, its assessment is limited by different tools and underlying differences in diagnostic criteria for gastrointestinal dysfunction. To date, there is no psychometric instrument for quantitative evaluation of gastrointestinal symptoms specifically designed for use in PD. OBJECTIVE:The objective of this study was to develop a self-report questionnaire-based instrument, the Gastrointestinal Dysfunction Scale for Parkinson's Disease, and to evaluate its psychometric properties. METHODS:We performed a literature review and conducted 3 focus groups to develop the Gastrointestinal Dysfunction Scale for Parkinson's Disease. Three hundred and sixteen patients with PD and 55 controls completed the Gastrointestinal Dysfunction Scale for Parkinson's Disease, the Non-Motor Symptom Scale, the Hospital Anxiety and Depression Scale, and a stool diary adapted from the Bristol Stool Chart. RESULTS:The Gastrointestinal Dysfunction Scale for Parkinson's Disease demonstrated good internal consistency (Cronbach's α = 0.82) and test-retest stability (0.79 < ICCs > 0.94). Correlation analyses supported good convergent and divergent validity. Receiver operating characteristic analysis demonstrated that a cutoff score of ≥9 on the Gastrointestinal Dysfunction Scale for Parkinson's Disease Constipation subscale discriminates between PD patients with and without constipation. CONCLUSIONS:The Gastrointestinal Dysfunction Scale for Parkinson's Disease is a novel disease-specific self-report tool to quantitatively assess the presence and severity of gastrointestinal dysfunction features in patients with PD, with strong reliability and validity. Further longitudinal studies are needed to demonstrate its utility in tracking gastrointestinal dysfunction in PD clinical cohorts. © 2021 International Parkinson and Movement Disorder Society.
10.1002/mds.28675
What influences placebo and nocebo responses in Parkinson's disease?
Witek Natalie,Stebbins Glenn T,Goetz Christopher G
Movement disorders : official journal of the Movement Disorder Society
Placebo treatment is associated with clinical improvements in many medical conditions, but is particularly important in Parkinson's disease because improvements are common, marked, and associated with objective neurochemical and neurophysiologic changes. This review will focus on the effect of the placebo in patients with PD and will discuss the pathophysiology, observed characteristics of motor and nonmotor placebo responses, and the patient and study characteristics that modify the placebo response. Similar to the placebo response, nocebo and lessebo effects alter clinical trial outcomes and impact conclusions. Whereas placebo-associated improvements are positively viewed by patients in clinical practice, they complicate clinical trials. The authors suggest strategies to reduce placebo effects during randomized placebo-controlled trials evaluating new therapies. © 2018 International Parkinson and Movement Disorder Society.
10.1002/mds.27416
The relevance of gender in Parkinson's disease: a review.
Picillo Marina,Nicoletti Alessandra,Fetoni Vincenza,Garavaglia Barbara,Barone Paolo,Pellecchia Maria Teresa
Journal of neurology
Since the official and systematic inclusion of sex and gender in biomedical research, gender differences have been acknowledged as important determinants of both the susceptibility to develop neurodegenerative diseases in general population and the clinical and therapeutic management of neurodegenerative patients. In this review, we gathered the available evidence on gender differences in Parkinson's disease (PD) regarding clinical phenotype (including motor and non-motor symptoms), biomarkers, genetics and therapeutic management (including pharmacological and surgical treatment). Finally, we will briefly discuss the role of estrogens in determining such differences. Several data demonstrate that PD in women starts with a more benign phenotype, likely due to the effect of estrogens. However, as the disease progresses, women are at higher risk of developing highly disabling treatment-related complications, such as motor and non-motor fluctuations as well as dyskinesia, compared with men. In addition, women have lower chances of receiving effective treatment for PD as deep brain stimulation. Taken together these findings challenge the definition of a more benign phenotype in women. Still, much work needs to be done to better understand the interaction between gender, genetics and environmental factors in determining the PD risk and clinical features. Improving our understanding in this field may result in implementation of strategies to identify prodromal PD and speed efforts to discern new directions for disease tailored treatment and management.
10.1007/s00415-016-8384-9
Functional MRI in Parkinson's disease with freezing of gait: a systematic review of the literature.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
BACKGROUND:Freezing of gait (FOG), a common and disabling symptom of Parkinson's disease (PD), is characterized by an episodic inability to generate effective stepping. Functional MRI (fMRI) has been used to evaluate abnormal brain connectivity patterns at rest and brain activation patterns during specific tasks in patients with PD-FOG. This review has examined the existing functional neuroimaging literature in PD-FOG, including those with treatment. Summarizing these articles provides an opportunity for a better understanding of the underlying pathophysiology in PD-FOG. METHODS:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a literature review of studies using fMRI to investigate the underlying pathophysiological mechanisms of PD-FOG. RESULTS:We initially identified 201 documents. After excluding the duplicates, reviews, and other irrelevant articles, 39 articles were finally identified, including 18 task-based fMRI studies and 21 resting-state fMRI studies. CONCLUSIONS:Studies using fMRI techniques to evaluate PD-FOG have found dysfunctional connectivity in widespread cortical and subcortical regions. Standardized imaging protocols and detailed subtypes of PD-FOG are furthered required to elucidate current findings.
10.1007/s10072-021-05121-5
Parkinson's Disease: A Tale of Many Players.
Medical principles and practice : international journal of the Kuwait University, Health Science Centre
In 2020, more than 9 million patients suffering from Parkinson's disease (PD) were reported worldwide, and studies predict that the burden of this disease will grow substantially in industrial countries. In the last decade, there has been a better understanding of this neurodegenerative disorder, clinically characterized by motor disturbances, impaired balance, coordination, memory difficulties, and behavioral changes. Various preclinical investigations and studies on human postmortem brains suggest that local oxidative stress and inflammation promote misfolding and aggregation of alpha-synuclein within Lewy bodies and cause nerve cell damage. Parallel to these investigations, the familial contribution to the disease became evident from studies on genome-wide association in which specific genetic defects were linked to neuritic alpha-synuclein pathology. As for treatment, currently available pharmacological and surgical interventions may improve the quality of life but do not stop the progress of neurodegeneration. However, numerous preclinical studies have provided insights into the pathogenesis of PD. Their results provide a solid base for clinical trials and further developments. In this review, we discuss the pathogenesis, the prospects, and challenges of synolytic therapy, CRISPR, gene editing, and gene- and cell-based therapy. We also throw light on the recent observation that targeted physiotherapy may help improve the gait and other motor impairments.
10.1159/000531422
Non-Genetic Risk Factors for Parkinson's Disease: An Overview of 46 Systematic Reviews.
Journal of Parkinson's disease
BACKGROUND:Numerous systematic reviews (SRs) and meta-analyses on non-genetic risk factors for Parkinson's disease (PD) development have been published with inconsistent conclusions. OBJECTIVE:This overview of SRs aimed to summarize evidence on non-genetic factors for the development of PD from the published SRs, and explore the reasons behind the conflicting results. METHODS:Three international databases were searched for SRs with meta-analyses summarized evidence on non-genetic factors for PD development. The Assessing the Methodological Quality of Systematic Reviews 2 tool was used to appraise the methodological quality of included SRs. Pooled effect estimations were extracted from each meta-analysis. RESULTS:Forty-six SRs covered six categories, and more than 80 factors were included in this overview. Thirty-nine SRs (84.7%) were judged to be of critically low methodological quality. Evidence from prospective studies showed that physical activity, smoking, coffee, caffeine, tea, fat intake, ibuprofen use, calcium channel blocker use, statin use, thiazolidinediones, and high serum urate levels significantly reduced the risk of PD, while dairy intake, diabetes, hormone replacement therapy, depression, mood disorder, bipolar disorder, and aspirin use significantly increased the risk of PD. Differences in study designs (e.g., cohort studies, case-control studies) accounted for the conflicting results among included SRs. CONCLUSION:Modifiable lifestyle factors such as physical activity and tea and coffee drinking may reduce the risk of PD, which may offer PD prevention strategies and hypotheses for future research. However, the designs of primary studies on PD risk factors and related SRs need to be improved and harmonized.
10.3233/JPD-202521
Role of Autophagy in Parkinson's Disease.
Cerri Silvia,Blandini Fabio
Current medicinal chemistry
Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation. Autophagy pathways include macroautophagy, chaperone-mediated autophagy and microautophagy, each involving different mechanisms of substrate delivery to lysosome. Defects of these pathways and the resulting accumulation of protein aggregates represent a common pathobiological feature of neurodegenerative disorders such as Alzheimer, Parkinson and Huntington disease. This review provides an overview of the role of autophagy in Parkinson's disease (PD) by summarizing the most relevant genetic and experimental evidence showing how this process can contribute to disease pathogenesis. Given lysosomes take part in the final step of the autophagic process, the role of lysosomal defects in the impairment of autophagy and their impact on disease will also be discussed. A glance on the role of non-neuronal autophagy in the pathogenesis of PD will be included. Moreover, we will examine novel pharmacological targets and therapeutic strategies that, by boosting autophagy, may be theoretically beneficial for PD. Special attention will be focused on natural products, such as phenolic compounds, that are receiving increasing consideration due to their potential efficacy associated with low toxicity. Although many efforts have been made to elucidate autophagic process, the development of new therapeutic interventions requires a deeper understanding of the mechanisms that may lead to autophagy defects in PD and should take into account the multifactorial nature of the disease as well as the phenotypic heterogeneity of PD patients.
10.2174/0929867325666180226094351
Parkinson's disease and anaesthesia.
Nicholson G,Pereira A C,Hall G M
British journal of anaesthesia
Parkinson's disease is an increasingly common disease of elderly patients who present a particular anaesthetic challenge. This review explores the epidemiology, aetiology, pathogenesis, and pathophysiology of the condition, particularly the possible role of genetic factors. The clinical features are described in detail and recent advances in medical management are highlighted. Controversies surrounding the use of the newer drugs and possible advances in neurosurgical interventions are discussed. Particular anaesthetic problems in patients with Parkinson's disease are respiratory, cardiovascular, and neurological. Potential drug interactions are described and recommendations are made about suitable anaesthetic techniques.
10.1093/bja/aef268
Advances in GBA-associated Parkinson's disease--Pathology, presentation and therapies.
Barkhuizen Melinda,Anderson David G,Grobler Anne F
Neurochemistry international
GBA mutations are to date the most common genetic risk factor for Parkinson's disease. The GBA gene encodes the lysomal hydrolase glucocerebrosidase. Whilst bi-allelic GBA mutations cause Gaucher disease, both mono- and bi-allelic mutations confer risk for Parkinson's disease. Clinically, Parkinson's disease patients with GBA mutations resemble idiopathic Parkinson's disease patients. However, these patients have a modest reduction in age-of-onset of disease and a greater incidence of cognitive decline. In some cases, GBA mutations are also responsible for familial Parkinson's disease. The accumulation of α-synuclein into Lewy bodies is the central neuropathological hallmark of Parkinson's disease. Pathologic GBA mutations reduce enzymatic function. A reduction in glucocerebrosidase function increases α-synuclein levels and propagation, which in turn inhibits glucocerebrosidase in a feed-forward cascade. This cascade is central to the neuropathology of GBA-associated Parkinson's disease. The lysosomal integral membrane protein type-2 is necessary for normal glucocerebrosidase function. Glucocerebrosidase dysfunction also increases in the accumulation of β-amyloid and amyloid-precursor protein, oxidative stress, neuronal susceptibility to metal ions, microglial and immune activation. These factors contribute to neuronal death. The Mendelian Parkinson's disease genes, Parkin and ATP13A2, intersect with glucocerebrosidase. These factors sketch a complex circuit of GBA-associated neuropathology. To clinically interfere with this circuit, central glucocerebrosidase function must be improved. Strategies based on reducing breakdown of mutant glucocerebrosidase and increasing the fraction that reaches the lysosome has shown promise. Breakdown can be reduced by interfering with the ability of heat-shock proteins to recognize mutant glucocerebrosidase. This underlies the therapeutic efficacy of certain pharmacological chaperones and histone deacetylase inhibitors. These therapies are promising for Parkinson's disease, regardless of mutation status. Recently, there has been a boom in studies investigating the role of glucocerebrosidase in the pathology of Parkinson's disease. This merits a comprehensive review of the current cell biological processes and pathological pictures involving Parkinson's disease associated with GBA mutations.
10.1016/j.neuint.2015.12.004
Parkinson's disease.
Barbosa E R,Limongi J C,Cummings J L
The Psychiatric clinics of North America
Parkinson's disease (PD) is one of the most common neurodegenerative diseases and affects 150 to 200 people per 100,000 population. Rapid advances have been made in the neurobiology of PD; this disorder is now recognized as a model of dysfunction in fronto-striatal circuits expressed by motor and behavioral symptoms. Several clinical and surgical strategies for the management of PD are discussed.
10.1016/s0193-953x(05)70344-0
Are genetic and idiopathic forms of Parkinson's disease the same disease?
Correia Guedes Leonor,Mestre Tiago,Outeiro Tiago F,Ferreira Joaquim J
Journal of neurochemistry
Genetic forms represent a small fraction of Parkinson's disease (PD) but their discovery has revolutionized research in the field, putting α-synuclein in the spotlight, and uncovering other key neuropathological mechanisms of the disease. The question of whether genetic and idiopathic PD (iPD) correspond to a same disease entity is not simply philosophical, has implications for the discovery of the biological background of PD and for the development of novel therapeutic strategies that may also be applicable to the larger iPD group. Here, we review the current landscape of what has been labeled genetic PD and critically discuss the rational for merging or separating genetic and idiopathic forms of PD as the same or different disease entities. We conclude by addressing the potential implications for future research.
10.1111/jnc.14902
Fatigue in Parkinson's disease and potential interventions.
Lou Jau-Shin
NeuroRehabilitation
BACKGROUND:Fatigue is common in patients with Parkinson's disease (PD). It occurs at every stage of PD and affects quality of life. Fatigue severity worsens over time as PD progresses, and it is associated with other non-motor symptoms such as apathy, depression, sleep disorder, and cognitive dysfunction. PURPOSE:In this literature review, I discuss the measurement and pathophysiology of fatigue and fatigability. There are no evidence-based treatments for fatigue and fatigability available. I review several pilot studies on the effects of pharmacological agents and exercise on fatigue and fatigability. These studies provide some insights on the design of future larger clinical trials. CONCLUSION:Fatigue inventories including The Fatigue Severity Scale, the Multidimensional Fatigue Inventory, or theParkinson Fatigue Scale are used to assess the severity of fatigue. Finger tapping and force generation are useful in quantifying physical fatigability. A reaction time paradigm such as the Attention Network Test can be used to measure cognitive fatigability. Physical fatigability is associated with the change in cortical excitability in PD measured by Transcranial Magnetic Stimulation. Cognitive fatigability is most likely associated with the neurotransmitter abnormalities (dopaminergic, cholinergic and noradrenergic) in PD. Levodopa, modafanil, methylphenidate, and rasagiline may be effective in treating fatigue and fatigability. Exercise programs may also be effective.
10.3233/NRE-151238
Pain in Parkinson's Disease: Pathophysiology, Classification and Treatment.
Journal of integrative neuroscience
Continuous medical progress is significantly improving the quality of health care. As a result, people are living longer than during the past century, but this has also caused an increase of the prevalence of many neurological disorders. Parkinson's disease (PD) is the fastest growing neurological condition, with a doubling of cases reported between 1995 and 2015 and a further doubling projected by 2030. Parkinson's disease is generally associated with characteristic motor symptoms (resting tremor, rigidity, bradykinesia and postural instability). However, patients with PD also experience many non-motor symptoms that might be at least as debilitating as the motor symptoms and which significantly impact patients' quality of life (QoL). Pain is a frequent yet underrecognized symptom; the incidence in PD is much higher than in the general population and constitutes a silent disability that significantly contributes to a deterioration in QoL. Accurate identification of parkinsonian pain is important for its diagnosis and effective treatment. In this review, we provide an overview of the pathophysiology, classification, and management of pain in PD. We define the various modalities of chronic PD pain, suggesting possible explanations for its relationship with PD pathology, and discuss its management and currently recommended therapies.
10.31083/j.jin2205132
The clinical heterogeneity of Parkinson's disease and its therapeutic implications.
The European journal of neuroscience
Although Parkinson's disease (PD) is primarily a movement disorder, there are a range of associated nonmotor symptoms, including cognitive impairment, depression and sleep disturbance. These can occur throughout the disease course, even predating the motor syndrome. However, both motor and nonmotor symptoms are variable between individual patients. Rate of disease progression is also heterogenous: although 50% have reached key milestones of either postural instability or dementia within 4 years from diagnosis, almost a quarter have a good prognosis at 10 years. In this review we discuss how a range of different factors including clinical features, pathology and genetics, have been used to describe the heterogeneity of PD. We explore the value of longitudinal studies of incident PD cohorts, based on our own experience in Cambridgeshire, to define differences in rates of disease progression and predictors of outcome, including how such studies have informed the development of prognostic models which can be used at an individual patient level. Finally, we discuss the benefits of better understanding the basis of heterogeneity of PD in terms of implications for the development and trialling of more targeted therapies for different subgroups of patients, including regenerative approaches.
10.1111/ejn.14094
Mood Disorders and Anxiety in Parkinson's Disease: Current Concepts.
Lintel Hendrik,Corpuz Timothy,Paracha Saif-Ur-Rahman,Grossberg George T
Journal of geriatric psychiatry and neurology
Mood disorders and anxiety significantly impact the prognosis and disease course of Parkinson's disease. Non-motor symptoms of Parkinson's disease such as apathy, anhedonia, and fatigue overlap with diagnostic criteria for anxiety and depression, thus making accurate diagnosis of mood disorders in Parkinson's disease patients difficult. Furthermore, treatment options for mood disorders can produce motor complications leading to poor adherence and impaired quality of life in Parkinson's disease patients. This review aims to clarify the current state of diagnostic and treatment options pertaining to anxiety and mood disorders in Parkinson's disease. It explores both the pharmacologic and non-pharmacologic treatment modalities for various mood disorders in comorbid Parkinson's disease with a brief discussion of the future outlook of the field given the current state of the literature.
10.1177/08919887211018267
Nonmotor Subtyping in Parkinson's Disease.
Sauerbier Anna,Rosa-Grilo Miguel,Qamar Mubasher A,Chaudhuri K Ray
International review of neurobiology
Nonmotor symptoms are integral to Parkinson's disease. Several subtypes dominated by specific nonmotor symptoms have emerged. In this chapter, the rationale behind nonmotor subtyping and currently proposed nonmotor subgroups within Parkinson's disease based on data-driven cluster analysis and clinical observations will be summarized. Furthermore, the concept of seven clinical nonmotor subtypes will be discussed in detail including the clinical presentation, potential biomarkers, and the clinical relevance. In future, nonmotor subtypes will possibly play a major role within the aim to achieve personalized medicine.
10.1016/bs.irn.2017.05.011
Treatment of Older Parkinson's Disease.
Lenka Abhishek,Padmakumar Chandrasekharapillai,Pal Pramod K
International review of neurobiology
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The prevalence of PD increases with age. The spectrum of clinical features, the rate of progression of the disease, the burden of nonmotor symptoms, and the response to medications are different in older patients with PD from the relatively younger patients. Management of symptoms of PD in older patients is challenging because of possible existence of several age-related systemic illness. While dealing with older patients, it is crucial not to attribute all the physical symptoms to PD. Thorough evaluation for existence of diseases such as normal pressure hydrocephalus and vascular parkinsonism which partially mimic the symptoms of PD carries immense importance. Medical management of parkinsonian symptoms should be preferred with levodopa monotherapy. However, in patients with significant motor fluctuations, dopaminergic agents may be added with caution, as they are notorious for several adverse reactions. Nonmotor symptoms must be provided high importance as they substantially worsen the quality of life. In addition to parkinsonian symptoms, older patients with PD may need to undergo surgery for several conditions. Meticulous perioperative management is crucial as older patients with PD may face several surgery-related complications compared to the younger patients. Compliance to treatment is an important issue in old age. Hence multidisciplinary approach to management of PD in older patients should be emphasized.
10.1016/bs.irn.2017.01.005
Does Parkinson's disease start in the gut?
Gershanik Oscar S
Arquivos de neuro-psiquiatria
Current understanding of the pathophysiology of Parkinson's disease suggests a key role of the accumulation of alpha-synuclein in the pathogenesis. This critical review highlights major landmarks, hypotheses and controversies about the origin and progression of synucleinopathy in Parkinson's disease, leading to an updated review of evidence suggesting the enteric nervous system might be the starting point for the whole process. Although accumulating and compelling evidence favors this theory, the remaining knowledge gaps are important points for future studies.
10.1590/0004-282X20170188
Does paraquat cause Parkinson's disease? A review of reviews.
Weed Douglas L
Neurotoxicology
To examine the extent to which a consensus exists in the scientific community regarding the relationship between exposure to paraquat and Parkinson's disease, a critical review of reviews was undertaken focusing on reviews published between 2006 and the present that offered opinions on the issue of causation. Systematic searches were undertaken of scientific databases along with searches of published bibliographies to identify English language reviews on the topic of paraquat and Parkinson's disease including those on the broader topic of environmental and occupational risk factors for Parkinson's disease. Of the 269 publications identified in the searches, there were twelve reviews, some with meta-analyses, that met the inclusion criteria. Information on methods used by the reviewers, if any, and source of funding was collected; the quality of the reviews was considered. No author of any published review stated that it has been established that exposure to paraquat causes Parkinson's disease, regardless of methods used and independent of funding source. A consensus exists in the scientific community that the available evidence does not warrant a claim that paraquat causes Parkinson's disease. Future research on this topic should focus on improving the quality of epidemiological studies including better exposure measures and identifying specific mechanisms of action. Future reviews of emerging evidence should be structured as systematic narrative reviews with meta-analysis if appropriate.
10.1016/j.neuro.2021.08.006
New markers in Parkinson's disease.
Bougea Anastasia
Advances in clinical chemistry
Parkinson's disease (PD) is a chronic, debilitating neurodegenerative disorder characterized clinically by a variety of progressive motor and nonmotor symptoms. Currently, there is a dearth of diagnostic tools available to predict, diagnose or mitigate disease risk or progression, leading to a challenging dilemma within the healthcare management system. The search for a reliable biomarker for PD that reflects underlying pathology is a high priority in PD research. Currently, there is no reliable single biomarker predictive of risk for motor and cognitive decline, and there have been few longitudinal studies of temporal progression. A combination of multiple biomarkers might facilitate earlier diagnosis and more accurate prognosis in PD. In this review, we focus on the recent developments of serial biomarkers for PD from a variety of clinical, biochemical, genetic and neuroimaging perspectives.
10.1016/bs.acc.2019.12.001
Biomarkers in Parkinson's disease: Advances and strategies.
Delenclos Marion,Jones Daryl R,McLean Pamela J,Uitti Ryan J
Parkinsonism & related disorders
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization.
10.1016/j.parkreldis.2015.09.048
Parkinson's disease.
Playfer J R
Postgraduate medical journal
Parkinson's disease is a common disabling disease of old age. The diagnosis of idiopathic Parkinson's disease is based on clinical signs and has poor sensitivity, with about 25% of patients confidently diagnosed as having the disease actually having other conditions such as multi-system atrophy and other parkinsonism-plus syndromes. Benign essential tremor and arteriosclerotic pseudo-parkinsonism can easily be confused with Parkinson's disease. The cause of Parkinson's disease remains unknown. Speculative research highlights the role of oxidative stress and free radical mediated damage to dopaminergic cells. Parkinson's disease is the one neurodegenerative disorder in which drugs have been demonstrated to be of value. There is now a wide variety of drugs and formulations available, including anticholinergics, amantidine, L-dopa, dopamine agonists including apomorphine, selegiline and soon to be available catechol-O-methyltransferase inhibitors. Disabling side-effects of treatment, fluctuations, dyskinesias and psychiatric problems require strategic use of the drugs available. There is an increasing potential for neurosurgical intervention.
10.1136/pgmj.73.859.257
Peripheral neuropathy in Parkinson's disease.
Paul Dion A,Qureshi Abdul Rehman M,Rana Abdul Qayyum
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Peripheral neuropathy (PN) is a common neurological problem defined as a dysfunction of sensory, motor, and autonomic nerves. The presence of peripheral neuropathy has recently been noticed in Parkinson's disease (PD) This comorbidity is concerning as it increases the burden on patients whose motor functions are previously compromised. A comprehensive computer-based literature review utilizing multiple peer-reviewed databases (e.g., Embase, PsycINFO, CINAHL, etc.) was conducted. There is evidence for the utility of robust diagnostic criteria to distinguish between large fiber neuropathy (LFN) and small fiber neuropathy (SFN). Some studies have established links between prolonged L-DOPA exposure and prevalence with increased levels of homocysteine (HCY) and methylmalonic acid (MMA) as pathological underlying mechanisms. PN in PD patients with relatively truncated exposure to L-DOPA therapy may have underlying mutations in the Parkin and MHTFR gene or separate mitochondrial disorders. Vitamin B12 and cobalamin deficiencies have also been implicated as drivers of PN. Accumulation of phosphorylated α-synuclein is another central feature in PN and deems urgent exploration via large cohort studies. Importantly, these underlying mechanisms have been linked to peripheral denervation. This review delves into the potential treatments for PN targeting B12 deficiencies and the use of COMT inhibitors along with other novel approaches. Avenues of research with powerful randomized controlled and long-term cohort studies exploring genetic mechanisms and novel treatment pathways is urgently required to alleviate the burden of disease exerted by PN on PD.
10.1007/s10072-020-04407-4
Relationships between deep brain stimulation and impulse control disorders in Parkinson's disease, with a literature review.
Shotbolt P,Moriarty J,Costello A,Jha A,David A,Ashkan K,Samuel M
Parkinsonism & related disorders
Impulse control disorders (ICDs) are behavioural/neuropsychiatric complications of the pharmacological treatment of Parkinson's disease. Long term motor complications of PD can be effectively treated using deep brain stimulation (DBS) of subcortical nuclei. The relationships between ICDs and DBS treatment of the motor complications of Parkinson's disease remain unclear. We describe 50 consecutive patients in whom detailed neuropsychiatric assessments were performed as part of our routine pre-operative assessment. Eight had current or past ICDs during pre-operative assessment. These patients were more likely to be male and were younger than those without ICDs. Other psychosocial variables did not predict the presence of ICDs. Detailed neuropsychological examination failed to show any between-group differences. Our prevalence rate of 16% helps raise awareness of ICDs in this specialised clinic population and may reflect common denominators between significant motor fluctuations and dopaminergic drug - related behavioural disturbances. Four patients were deemed suitable for surgery after multi-disciplinary assessment. One had re-emergence of his ICD 18 months post-operatively, the ICD having resolved in the first 18 months. We also review published literature and the evidence regarding post-operative outcomes. We recommend the routine pre-operative examination of patients for psychopathology and emphasize the importance of post-operative psychiatric surveillance.
10.1016/j.parkreldis.2011.08.016
Parkinson's disease: chameleons and mimics.
Ali Khalid,Morris Huw R
Practical neurology
Parkinson's disease (PD) is a common neurodegenerative condition that usually presents with symptoms related to asymmetric bradykinesia, resting tremor, rigidity and postural instability. Making the correct diagnosis can be challenging as many conditions-including tremor, gait and atypical parkinsonian disorders-can mimic PD. PD can present with unanticipated motor and non-motor symptoms, and so can masquerade as a number of rheumatological, neurological, sleep and mood disorders. Careful clinical assessment, informed by well-validated diagnostic criteria, is important in the initial diagnostic formulation. In uncertain or ambiguous cases, follow-up with monitoring of the treatment response usually gives the correct diagnosis, as validated in postmortem follow-up studies. 'Premotor' PD-a range of non-motor symptoms, particularly sleep disorders and constipation, which can occur up to 20 years before PD motor onset-is common. The presence of non-motor features in early disease sometimes supports the diagnosis of PD. Here we give an overview of the diagnosis of PD and its most important chameleons and mimics, and review the recent advances in structural and functional imaging in parkinsonism.
10.1136/practneurol-2014-000849
'Atypical' Parkinson's disease - genetic.
Weissbach Anne,Wittke Christina,Kasten Meike,Klein Christine
International review of neurobiology
Genetic atypical Parkinson's disease (PD) describes monogenic forms of PD that resemble idiopathic PD but feature prominent atypical clinical signs and symptoms and can be sub-grouped into i) atypical monogenic forms caused by mutations in the ATP13A2, DNAJC6, FBXO7, SYNJ1, VPS13C, and DCTN genes; ii) monogenic PD more closely resembling idiopathic PD, but associated with atypical features in at least a subset of cases (SNCA-, LRRK2-, VPS35-, Parkin-, PINK1-, and DJ-1-linked PD; iii) carriers of mutations in genes that are usually associated with other movement disorders but may present with parkinsonism, such as dopa-responsive dystonia. Some atypical features are shared by almost all forms, such as an overall early age at onset. Other clinical signs are present in carriers of mutations across several different genes, such as for example, early cognitive decline. Finally, several clinical features can serve as red flags for specific forms of atypical PD including a supranuclear gaze palsy in ATP13A2 mutation carriers or hypoventilation linked to mutations in the DCTN1 gene.
10.1016/bs.irn.2019.10.011
Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature.
Behavioural neurology
Background:Neuropsychiatric symptoms (NPS) are a common and potentially serious manifestation of Parkinson's disease (PD) but are frequently overlooked in favor of a focus on motor symptomatology. Here, we conducted a literature review of the prevalence and type of NPS experienced by PD patients with a clinically defined course of their illness. Methods:We identified reports of NPS in patients with PD and mean disease duration over 3 years. Three databases-PubMed, Scopus, and Dialnet-were searched for relevant literature published between 2010 and 2020. Predefined exclusion criteria were applied prior to a descriptive analysis of the literature base. Results:In all, 87 unique reports were identified and 30 met inclusion and exclusion criteria. These included 7142 patients with PD (male: 67.3%; mean age: 66.2 years; mean disease duration: 6.7 years). The most frequent NPS were mood disorders (apathy, depression, and anxiety), psychosis, and impulse control disorders (ICD). Treatment with dopamine agonists was identified as an important risk factor for ICD. Co-occurrence of NPS and cognitive dysfunction was also evidenced in a number of studies. Patients with more significant cognitive deficits and higher levels of NPS appeared to be of older age with a longer disease duration and to have more severe motor symptoms. Conclusions:NPS, most commonly mood disorders (apathy, depression, and anxiety), psychosis, and ICDs are frequent manifestations of PD. The results of this review reflect the need to develop unified validated assessment protocols for NPS in PD, as well as to improve their management in clinical practice.
10.1155/2022/1213393
Patients with Parkinson's Disease and Myasthenia Gravis-A Report of Three New Cases and Review of the Literature.
Odajiu Irina,Davidescu Eugenia Irene,Mitu Cristina,Popescu Bogdan Ovidiu
Medicina (Kaunas, Lithuania)
Neurodegenerative diseases such as Parkinson's disease (PD)have increasing incidence, due to lifespan expansion. The association between PD and Myasthenia Gravis (MG) is uncommon, and so far, since 1987, 26 cases have been reported. We report here a series of three new cases, two men and one woman with this peculiar combination of conditions, identified in the Neurology Department of Colentina Clinical Hospital. In this article, the pathogenesis of MG in patients with PD is discussed, along with a literature review regarding the co-occurrence of these two neurological diseases.
10.3390/medicina56010005
'Atypical' Parkinson's disease - sporadic.
Zeuner Kirsten E,Berg Daniela
International review of neurobiology
Parkinson's disease still is a clinical diagnosis. Also, the MDS Clinical Diagnostic Criteria for Parkinson's disease published in 2015 are based on clinical characteristics and were designed codifying the diagnostic process of an expert. The purpose was to support less experienced neurologists to achieve the diagnostic procedure up to the level of an expert. The criteria include both negative and positive properties. However, some features exclude patients with typical Parkinson's disease mainly during their early or late stages. These includes symptoms such as the absence of the combination of typical motor symptoms, the insufficient response to dopaminergic treatment, autonomic dysfunction, dystonia, postural instability or cognitive impairment. This chapter discusses those "atypical" symptom constellations that complicate the differential diagnosis of PD versus atypical parkinsonism and illustrates additional considerations that might be helpful to achieve a correct diagnosis.
10.1016/bs.irn.2019.10.002
Parkinson's disease, antiparkinson medicines, and driving.
Álvarez F Javier
Expert review of neurotherapeutics
INTRODUCTION:Parkinson's disease is a progressive neurodegenerative disorder with multiple motor and non-motor features. It is well known that the ability to drive safely is impaired in Parkinson's disease patients. While the impairing effects on psychomotor performance and vision are well established, there is uncertainty about the increased risk of road traffic accidents among drivers with Parkinson's disease. These issues, considering the progressive nature of Parkinson's disease, comorbidities and the profile of unwanted effects of the pharmacological treatments used, indicate that driving automobiles is a unique concern. AREAS COVERED:The Driving under the Influence of Drugs, Alcohol and Medicines (DRUID) categorization and specific advice for medications used in treating Parkinson's disease are presented. Expert commentary: Most medicines currently in use are considered DRUID category II: Likely to produce moderate effects on fitness to drive. Health professionals treating Parkinson's disease patients must be involved in providing proper advice and information to the patient, family and caregivers on the effects of the disorder and its medications on driving, and all possible actions should be undertaken to transition drivers with Parkinson's disease from driving to non-driving.
10.1080/14737175.2016.1218278
Parkinson's disease between internal medicine and neurology.
Journal of neural transmission (Vienna, Austria : 1996)
General medical problems and complications have a major impact on the quality of life in all stages of Parkinson's disease. To introduce an effective treatment, a comprehensive analysis of the various clinical symptoms must be undertaken. One must distinguish between (1) diseases which arise independently of Parkinson's disease, and (2) diseases which are a direct or indirect consequence of Parkinson's disease. Medical comorbidity may induce additional limitations to physical strength and coping strategies, and may thus restrict the efficacy of the physical therapy which is essential for treating hypokinetic-rigid symptoms. In selecting the appropriate medication for the treatment of any additional medical symptoms, which may arise, its limitations, contraindications and interactions with dopaminergic substances have to be taken into consideration. General medical symptoms and organ manifestations may also arise as a direct consequence of the autonomic dysfunction associated with Parkinson's disease. As the disease progresses, additional non-parkinsonian symptoms can be of concern. Furthermore, the side effects of Parkinson medications may necessitate the involvement of other medical specialists. In this review, we will discuss the various general medical aspects of Parkinson's disease.
10.1007/s00702-015-1443-z
Parkinson's: a syndrome rather than a disease?
Titova Nataliya,Padmakumar C,Lewis Simon J G,Chaudhuri K Ray
Journal of neural transmission (Vienna, Austria : 1996)
Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.
10.1007/s00702-016-1667-6
Nutritional aspects in Parkinson's disease.
Critical reviews in food science and nutrition
The links between diet and Parkinson's disease (PD) are unclear and incomprehensible. However, numerous studies have demonstrated the correlation between diet, nutrients and health condition in PD patients. They indicate the possibility of management of the disease, which might be possible through nutrition. Pharmaceutical treatment as well as a complementary holistic approach to the patients should be considered. It is of critical importance to understand how the diet and nutrients might influence PD. A better understanding of the relationship between diet and PD could help to better manage the disease explain promising therapeutic approaches, minimize motor and nonmotor symptoms and disease progression based on a personalized diet. In this review, the recent literature on the observed nutrition disorders and the possible role of diet and nutrients in the prevention and potential regression of PD, as well as dietary interventions and supplementation used to manage the disease is revised.
10.1080/10408398.2021.1902261
Parkinson's disease: Diagnosis and appreciation of comorbidities.
Deeb Wissam,Nozile-Firth Kamilia,Okun Michael S
Handbook of clinical neurology
Parkinson's disease (PD) is a complex neuropsychiatric disorder that manifests with a variety of motor and nonmotor symptoms. Its incidence increases with age. It is important for clinicians to be able to distinguish symptoms of aging and other comorbidities from those of PD. The diagnosis of PD has traditionally been rendered using strict criteria that mainly rely on the cardinal motor symptoms of rest tremor, rigidity, and bradykinesia. However, newer diagnostic criteria proposed by the Movement Disorders Society for diagnosis of PD collectively reflect a greater appreciation for the nonmotor symptoms. The treatment of PD remains symptomatic and the most noticeable improvements have been documented in the motor symptoms. Levodopa remains the gold standard for therapy, however there are now many other potential medical and surgical treatment strategies. Nonmotor symptoms have been shown to affect quality of life more than the motor symptoms. There is ongoing research into symptomatic and disease modifying treatments. Given the multisystem involvement in PD, an interdisciplinary patient-centered approach is recommended by most experts. This chapter addresses first the diagnostic approach and the many geriatric considerations. This is followed by a review of the nonmotor symptoms. Finally, a summary of current treatment strategies in PD is presented along with potential treatment complications.
10.1016/B978-0-12-804766-8.00014-5
Apathy in Parkinson's Disease.
Pagonabarraga Javier,Kulisevsky Jaime
International review of neurobiology
The normal maintenance of human motivation depends on the integrity of subcortical structures that link the medial and lateral prefrontal cortex with the limbic system. Apathy is highly prevalent in Parkinson's disease and causes major impact on the quality of life of patients and caregivers, comparable to depression or cognitive impairment. The clinical differentiation of apathy from the emotional symptoms of depression, and from difficulties in planning or organizing mental programs as a consequence of executive dysfunction, may guide a rationale for individualized treatment approach of apathetic symptoms, which is presently lacking. To review the different apathetic syndromes that can be diagnosed in clinical practice by appropriate scales, as well as the brain systems that subserve each syndrome, helps to explain how dopaminergic, antidepressant, or cholinergic medications may lead to individual improvements in apathy.
10.1016/bs.irn.2017.05.025
Parkinson's disease.
Béné Raphael,Antić Sonja,Budisić Mislav,Lisak Marijana,Trkanjec Zlatko,Demarin Vida,Podobnik-Sarkanji Slava
Acta clinica Croatica
Parkinson's disease is one of the most common neurodegenerative diseases caused by degeneration of dopaminergic neurons in substantia nigra. The neuropathologic hallmark of Parkinson's disease is the presence of Lewy bodies composed mostly of alpha-synuclein and ubiquitin. It is believed that the occurrence of Parkinson's disease is due to a combination of genetic and environmental factors, but the exact mechanism of Parkinson's disease development is not fully elucidated. The most characteristic motor symptoms for Parkinson's disease include bradykinesia, rigidity, resting tremor and postural instability, while many patients also have non-motor signs and symptoms. The key therapeutic agent in the treatment of Parkinson's disease is L-dopa, and the others are dopaminergic agents, monoamine oxidase-B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, amantadine and anticholinergic agents.
Metabolomics in Parkinson's disease.
Troisi Jacopo,Landolfi Annamaria,Cavallo Pierpaolo,Marciano Francesca,Barone Paolo,Amboni Marianna
Advances in clinical chemistry
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder in which environmental (lifestyle, dietary, infectious disease) factors as well as genetic make-up play a role. Metabolomics, an evolving research field combining biomarker discovery and pathogenetics, is particularly useful in studying complex pathophysiology in general and Parkinson's disease (PD) specifically. PD, the second most frequent neurodegenerative disorder, is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of intraneural inclusions of α-synuclein aggregates. Although considered a predominantly movement disorder, PD is also associated with number of non-motor features. Metabolomics has provided useful information regarding this neurodegenerative process with the aim of identifying a disease-specific fingerprint. Unfortunately, many disease variables such as clinical presentation, motor system involvement, disease stage and duration substantially affect biomarker relevance. As such, metabolomics provides a unique approach to studying this multifactorial neurodegenerative disorder.
10.1016/bs.acc.2020.09.003
Misperceptions and Parkinson's disease.
Friedman Joseph H
Journal of the neurological sciences
Most of the neurobehavioral aspects of Parkinson's disease have been well established and studied, but many are not well known, and hardly studied. This article focuses on several behavioral abnormalities that are common, and frequently cause difficulty for the patient and family due to lack of recognition as part of the disease. While it is well known that L-Dopa dyskinesias are frequently not recognized or under appreciated by patients, a similar lack of recognition may affect the patient's own speech volume, where their center of gravity is located, whether they are tilted to one side, and their under-recognition of others' emotional displays. In addition, PD patients are often misperceived by others incorrect impression of their emotional and cognitive state based purely on facial expression. These changes and others are briefly reviewed.
10.1016/j.jns.2016.12.059
Comparison of Awake and Asleep Deep Brain Stimulation for Parkinson's Disease: A Detailed Analysis Through Literature Review.
Wang Jun,Ponce Francisco A,Tao Jun,Yu Hong-Mei,Liu Ji-Yuan,Wang Yun-Jie,Luan Guo-Ming,Ou Shao-Wu
Neuromodulation : journal of the International Neuromodulation Society
OBJECTIVES:Deep brain stimulation (DBS) for Parkinson's disease (PD) has been applied to clinic for approximately 30 years. The goal of this review is to explore the similarities and differences between "awake" and "asleep" DBS techniques. METHODS:A comprehensive literature review was carried out to identify relevant studies and review articles describing applications of "awake" or "asleep" DBS for Parkinson's disease. The surgical procedures, clinical outcomes, costs and complications of each technique were compared in detail through literature review. RESULTS:The surgical procedures of awake and asleep DBS surgeries rely upon different methods for verification of intended target acquisition. The existing research results demonstrated that the stereotactic targeting accuracy of lead placement obtained by either method is reliable. There were no significant differences in clinical outcomes, costs, or complications between the two techniques. CONCLUSION:The surgical and clinical outcomes of asleep DBS for PD are comparable to those of awake DBS.
10.1111/ner.13061
Capgras syndrome in Parkinson's disease: two new cases and literature review.
Cannas Antonino,Meloni Mario,Mascia Marcello Mario,Solla Paolo,Cocco Luigi,Muroni Antonella,Floris Gianluca,Di Stefano Francesca,Marrosu Francesco
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
The Capgras syndrome (CS) is a rare psychiatric disorder. CS is classified as a delusional misidentification syndrome. Initially, CS was described in paranoid schizophrenia and schizoaffective disorders. CS has also been reported in neurodegenerative diseases such as Alzheimer's disease and Lewy body dementia. To date, there are very few descriptions of the occurrence of CS in idiopathic Parkinson's disease (PD), with or without dementia. Considering the recent observation of two new cases in PD patients, a systematic overview of the literature published between 1976 and 2016 reporting CS in PD was conducted. The purpose of this article is to examine the phenomenon in people with PD with and without dementia, the psychopathologic context in which it happened, the role played by the dopaminergic medications and to define useful therapeutic strategies. Our CS cases occurred in two elderly patients with advanced PD and cognitive impairment, respectively, after an acute stressor event and after an increase of the total daily dose of levodopa. In light of our observations and the cases reported in the literature, we argue that CS is an acute or subacute psychotic disorder occurring mostly in PD with dementia. Besides, the increase in brain dopamine levels induced by acute stressful events and/or dopamine-enhancing medications should be considered as a possible causal mechanism of CS in patients with advanced stages of PD and cognitive decline.
10.1007/s10072-016-2765-9
Parkinsonism-Hyperpyrexia Syndrome and Dyskinesia-Hyperpyrexia Syndrome in Parkinson's Disease: Two Cases and Literature Review.
Journal of Parkinson's disease
Parkinsonism-hyperpyrexia syndrome (PHS) and dyskinesia-hyperpyrexia syndrome (DHS) are rare but exhibit life-threatening complications in Parkinson's disease (PD). We herein presented two cases of PD patients and performed a comprehensive and comparative literature review for these two syndromes. The first case was diagnosed as PHS with cerebral salt wasting syndrome caused by abrupt withdrawal of antiparkinsonian medication. Her symptoms were gradually remitted with reinstitution of the medication. The second one was an early-stage PD patient diagnosed as DHS in association with abuse of antiparkinsonian drugs. Her symptoms were gradually remitted with reduced dosage of dopaminergic drugs. Results of literature reviews revealed a total of 56 and 13 cases of PHS and DHS, respectively, and they were more likely to occur in elderly and long-term PD patients. These two syndromes showed different female-to-male ratio, similar mortality, and different recovery time. There were stark differences between PHS and DHS, including triggers (abrupt drug stoppage versus drug abuse), symptoms (worsened tremor and rigidity versus continuous dyskinesia), and treatment (drug reinstitution versus drug reduction). In summary, our reports and the review provide new insights into PHS and DHS in association with PD and may facilitate rapid discrimination of the syndromes for timely and proper treatment to reduce mortality.
10.3233/JPD-223362
Pain in Parkinson's disease: analysis and literature review.
Rana Abdul Qayyum,Kabir Ashish,Jesudasan Margaret,Siddiqui Ishraq,Khondker Sumaiya
Clinical neurology and neurosurgery
Pain is a common problem faced by Parkinson's disease (PD) patients. Despite its impact and disabling effects pain is still frequently overlooked. In this study we analyze a representative sample of peer reviewed literature for the prevalence and types of pain in PD, the impact and significance of pain in the quality of life of the PD patient and the challenges inherent in the diagnosis and management of pain in PD patients. We compared and analyzed the findings of articles indexed in the PubMed database which looked at symptoms reported by large cohorts of PD patients. These articles all reported the incidence, nature and quality of pain in these patients and described the effects of pain on quality of life and generally were cross-sectional, retrospective or case-control studies, though a major pharmacoepidemiological design study was also analyzed. Results of our analysis showed that the pain was prevalent in 59.77% of PD patients. Five different types of pain were reported by PD patients--dystonia, musculoskeletal pain, nerve/nerve root pain, primary/central pain and according to some, akathisia. Patients who reported pain symptoms were also significantly more likely to report associated depression and a decreased quality of life. Many PD patients also reported poor management of pain and lower analgesic use than would be expected. We further discuss some of the possible approaches toward the development of a treatment algorithm regarding the management of pain in PD. We conclude that pain in is an under-recognized and under treated symptom in PD patients. Effective management of pain in PD patients would significantly improve their quality of life. Our analysis is in line with current thinking that identifies PD is much more of a multisystem disease with non-motor symptoms than previously thought.
10.1016/j.clineuro.2013.08.022
Premotor, nonmotor and motor symptoms of Parkinson's Disease: A new clinical state of the art.
Ageing research reviews
Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.
10.1016/j.arr.2022.101834
Biomarkers for Parkinson's Disease: How Good Are They?
Li Tianbai,Le Weidong
Neuroscience bulletin
Parkinson's disease (PD) is a complex neurodegenerative disorder with no cure in sight. Clinical challenges of the disease include the inability to make a definitive diagnosis at the early stages and difficulties in predicting the disease progression. The unmet demand to identify reliable biomarkers for early diagnosis and management of the disease course of PD has attracted a lot of attention. However, only a few reported candidate biomarkers have been tried in clinical practice at the present time. Studies on PD biomarkers have often overemphasized the discovery of novel identity, whereas efforts to further evaluate such candidates are rare. Therefore, we update the new development of biomarker discovery in PD and discuss the standard process in the evaluation and assessment of the diagnostic or prognostic value of the identified potential PD biomarkers in this review article. Recent developments in combined biomarkers and the current status of clinical trials of biomarkers as outcome measures are also discussed. We believe that the combination of different biomarkers might enhance the specificity and sensitivity over a single measure that might not be sufficient for such a multiplex disease.
10.1007/s12264-019-00433-1
Overview of Parkinson's disease.
Lew Mark
Pharmacotherapy
This overview of Parkinson's disease is designed to serve as a background to the discussion elsewhere in this supplement on the pharmacotherapy used in its management. Parkinson's disease is a common progressive neurodegenerative condition associated with significant disability and negative impact on quality of life. Although the cause of Parkinson's disease is unknown, the pathologic manifestation involves the loss or dysfunction of dopaminergic neurons in the substantia nigra pars compacta. Characteristic clinical manifestations include difficulty with coordinated movement such as asymmetric resting tremor, rigidity, and bradykinesia. These symptoms and their response to levodopa constitute the basis for a clinical diagnosis of Parkinson's disease. Postural instability and gait abnormalities occur in more advanced disease. Although there is no cure for Parkinson's disease, a number of pharmacologic treatments are available for managing the motor and nonmotor symptoms. Research is under way to assess the disease-modifying ability of both standard and newer treatments.
10.1592/phco.27.12part2.155S
Animal Model for Prodromal Parkinson's Disease.
Taguchi Tomoyuki,Ikuno Masashi,Yamakado Hodaka,Takahashi Ryosuke
International journal of molecular sciences
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, but various non-motor symptoms (NMS) often precede motor symptoms. Recently, NMS have attracted much attention as a clue for identifying patients in a prodromal stage of PD, which is an excellent point at which to administer disease-modifying therapies (DMTs). These prodromal symptoms include olfactory loss, constipation, and sleep disorders, especially rapid eye movement sleep behavior disorder (RBD), all of which are also important for elucidating the mechanisms of the initiation and progression of the disease. For the development of DMTs, an animal model that reproduces the prodromal stage of PD is also needed. There have been various mammalian models reported, including toxin-based, genetic, and alpha synuclein propagation models. In this article, we review the animal models that exhibit NMS as prodromal symptoms and also discuss an appropriate prodromal model and its importance for the development of DMT of PD.
10.3390/ijms21061961
Young-onset Parkinson's disease: Its unique features and their impact on quality of life.
Mehanna Raja,Jankovic Joseph
Parkinsonism & related disorders
Young-onset Parkinson's disease (YOPD), defined as age at onset between 21 and 40 years, presents unique motor and non-motor features that differentiate this subtype from the typical late onset Parkinson's disease (LOPD), starting after age 61. Because it affects patients in the prime of their life, it often has an extraordinary impact on their family, social, and professional life. While typically progressing at a slower rate than LOPD, patients with YOPD are more prone to develop levodopa-related motor complications, including dyskinesia. In this article we will review the clinical features and epidemiology of YOPD with focus on its impact on pregnancy, employment and family, as well as its particular diagnostic and management challenges.
10.1016/j.parkreldis.2019.06.001
Sex and Gender Differences in Parkinson's Disease.
Neurologic clinics
The lower prevalence of Parkinson disease (PD) in females is not well understood but may be partially explained by sex differences in nigrostriatal circuitry and possible neuroprotective effects of estrogen. PD motor and nonmotor symptoms differ between sexes, and women experience disparities in care including undertreatment with DBS and less access to caregiving. Our knowledge about PD in gender diverse individuals is limited. Future studies should improve our understanding of the role of hormone replacement therapy in PD, address gender-based inequities in PD care and expand our understanding of PD in SGM and marginalized communities.
10.1016/j.ncl.2022.12.001
Gastrointestinal dysfunction in Parkinson's disease.
Fasano Alfonso,Visanji Naomi P,Liu Louis W C,Lang Antony E,Pfeiffer Ronald F
The Lancet. Neurology
Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.
10.1016/S1474-4422(15)00007-1
Palliative care for Parkinson's disease.
Ng Jeffrey Sheung Ching
Annals of palliative medicine
Parkinson's disease (PD) is a slowly progressive multi-system neurodegenerative disorder, with no available disease-modifying treatment. The disease is associated with motor and non-motor symptoms leading to impaired quality of life, disability and signi cant caregiver distress. Patients with PD bene t from palliative care which provides a holistic approach to meet their multi-faceted needs, including symptom control, communication needs and caregiver support. This article would review on recent articles addressing palliative care for PD.
10.21037/apm.2017.12.02
Awareness and current knowledge of Parkinson's disease: a neurodegenerative disorder.
Khan Asmat Ullah,Akram Muhammad,Daniyal Muhammad,Zainab Rida
The International journal of neuroscience
CONTEXT:Parkinson's disease (PD) is the second common progressive neurodegenerative disease, distressing older men and is prevalent Worldwide. OBJECTIVES:This article is aimed to review the epidemiology, etiology, pathogenesis, clinical manifestation, diagnosis and management of PD. METHODS:A google search was performed to recognise studies that review the characteristics of PD. Search terms included 'Parkinson's disease', 'epidemiology', 'etiology', 'pathogenesis', 'clinical manifestations', 'diagnosis' and 'management of Parkinson disease'. RESULTS:PD is linked to factors such as environmental chemicals, aging, family history and pesticide exposure such as the use of synthetic heroin. PD is characterised clinically by tremors at rest, postural instability, expressionless countenance, lead pipe rigidity and less commonly cognitive impairment. After 60 years of age, PD is commonly prevalent in 1-% of the population, no racial differences are apparent, but the prevalence of PD is more common in men than women. There has also been a better understanding that the disorder may be linked with major non-motor trouble in addition to the additional generally recognised motor complications. There are various management options for the timely management of PD. As the ailment advances, further management strategies are existing; however, the management of non-motor manifestations and late stage motor complications remains mainly testing and will advantage from additional clinical studies. CONCLUSIONS:In this article, we have discussed current progress in the understanding of the epidemiology, clinical manifestations, pathogenesis and management strategies of the disease.
10.1080/00207454.2018.1486837
Systematic review for the prevention and management of falls and fear of falling in patients with Parkinson's disease.
Brain and behavior
OBJECTIVE:To synthesize recent empirical evidence for the prevention and management of falls and fear of falling in patients with Parkinson's disease (PD). DATA SOURCE:Database from PubMed, Cochrane Library, and EMBASE. STUDY DESIGN:Systematic review. DATA COLLECTION:We searched the PubMed, Cochrane Library, and EMBASE databases for studies published from inception to February 27, 2021. Inclusion criteria were nonreview articles on prevention and management measures related to falls and fall prevention in Parkinson's disease patients. PRINCIPAL FINDINGS:We selected 45 articles and conducted in-depth research and discussion. According to the causes of falls in PD patients, they were divided into five directions, namely physical status, pre-existing conditions, environment, medical care, and cognition. In the cognitive domain, we focused on the fear of falling. On the above basis, we constructed a fall prevention model, which is a tertiary prevention health care network, based on The Johns Hopkins Fall Risk Assessment Tool to provide ideas for the prevention and management of falling and fear of falling in PD patients in clinical practice CONCLUSIONS: Falls and fear of falls in patients with Parkinson's disease can be reduced by effective clinical prevention and management. Future studies are needed to explore the efficacy of treatment and prevention of falls and fear of falls.
10.1002/brb3.2690
The initial diagnosis and management of Parkinson's disease.
Australian journal of general practice
BACKGROUND:Parkinson's disease is a common, progressive neurodegenerative disorder, the prevalence of which is on the rise. The diagnosis and management of Parkinson's disease is therefore likely to become increasingly frequent in general practice. OBJECTIVE:The aim of this article is to provide a practical overview for the general practitioner of the initial diagnosis and management of Parkinson's disease. DISCUSSION:Parkinson's disease is a multisystem disorder, and the way the diagnosis is delivered, as well as the early management, can have a lasting impact on the patient experience. In this article, the authors present their preferred approach to diagnosis and initial treatment, while highlighting common pitfalls and some useful simple strategies for communicating the diagnosis.
10.31128/AJGP-07-21-6087
Consensus on the treatment of dysphagia in Parkinson's disease.
Schindler Antonio,Pizzorni Nicole,Cereda Emanuele,Cosentino Giuseppe,Avenali Micol,Montomoli Cristina,Abbruzzese Giovanni,Antonini Angelo,Barbiera Filippo,Benazzo Marco,Benarroch Eduardo,Bertino Giulia,Clavè Pere,Cortelli Pietro,Eleopra Roberto,Ferrari Chiara,Hamdy Shaheen,Huckabee Maggie-Lee,Lopiano Leonardo,Marchese-Ragona Rosario,Masiero Stefano,Michou Emilia,Occhini Antonio,Pacchetti Claudio,Pfeiffer Ronald F,Restivo Domenico A,Rondanelli Mariangela,Ruoppolo Giovanni,Sandrini Giorgio,Schapira Anthony,Stocchi Fabrizio,Tolosa Eduardo,Valentino Francesca,Zamboni Mauro,Zangaglia Roberta,Zappia Mario,Tassorelli Cristina,Alfonsi Enrico
Journal of the neurological sciences
BACKGROUND:Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD. OBJECTIVE:To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management. METHODS:A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. RESULTS:The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed. CONCLUSIONS:The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists.
10.1016/j.jns.2021.120008
Parkinson's disease psychosis: presentation, diagnosis and management.
Schneider Ruth B,Iourinets Julia,Richard Irene H
Neurodegenerative disease management
Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor symptoms. Psychosis is a common feature of Parkinson's disease. Parkinson's disease psychosis (PDP) encompasses minor phenomena (illusions, passage hallucinations and presence hallucinations), visual and nonvisual hallucinations and delusions. PDP is associated with reduced function and quality of life. The initial management approach should focus on identification and treatment of any contributory medical factors, reduction or discontinuation of medications with potential to induce or worsen psychosis, nonpharmacological strategies and consideration of acetylcholinesterase inhibitor treatment in the setting of dementia. Pimavanserin, quetiapine and clozapine may all be considered for use in PDP. In this review, we discuss the presentation, diagnosis and management of PDP.
10.2217/nmt-2017-0028
Covid-19 and Parkinson's disease: an overview.
Cartella S M,Terranova C,Rizzo V,Quartarone A,Girlanda P
Journal of neurology
In March 2020, WHO declared Covid-19 outbreak pandemic. There has been increasing evidence that frail, old, multi-pathological patients are at greater risk of developing severe Covid-19 infection than younger, healthy ones. Covid-19's impact on Parkinson's Disease (PD) patients could be analysed through both the influence on PD patients' health and their risk of developing severe Covid-19, and the consequences of lockdown and restrictive measures on mental and cognitive health on both patients and caregivers. Moreover, there are critical issues to be considered about patients' care and management through an unprecedented time like this. One important issue to consider is physiotherapy, as most patients cannot keep exercising because of restrictive measures which has profoundly impacted on their health. Lastly, the relationship between PD and Sars-Cov2 may be even more complicated than it seems as some studies have hypothesized a possible Covid-19-induced parkinsonism. Hereby, we review the state of the art about the relationship between Covid-19 and Parkinson's Disease, focusing on each of these five points.
10.1007/s00415-021-10721-4
The hallmarks of Parkinson's disease.
Antony Paul M A,Diederich Nico J,Krüger Rejko,Balling Rudi
The FEBS journal
Since the discovery of dopamine as a neurotransmitter in the 1950s, Parkinson's disease (PD) research has generated a rich and complex body of knowledge, revealing PD to be an age-related multifactorial disease, influenced by both genetic and environmental factors. The tremendous complexity of the disease is increased by a nonlinear progression of the pathogenesis between molecular, cellular and organic systems. In this minireview, we explore the complexity of PD and propose a systems-based approach, organizing the available information around cellular disease hallmarks. We encourage our peers to adopt this cell-based view with the aim of improving communication in interdisciplinary research endeavors targeting the molecular events, modulatory cell-to-cell signaling pathways and emerging clinical phenotypes related to PD.
10.1111/febs.12335
Dysphagia in Parkinson's Disease.
Suttrup Inga,Warnecke Tobias
Dysphagia
More than 80 % of patients with Parkinson's disease (PD) develop dysphagia during the course of their disease. Swallowing impairment reduces quality of life, complicates medication intake and leads to malnutrition and aspiration pneumonia, which is a major cause of death in PD. Although the underlying pathophysiology is poorly understood, it has been shown that dopaminergic and non-dopaminergic mechanisms are involved in the development of dysphagia in PD. Clinical assessment of dysphagia in PD patients is challenging and often delivers unreliable results. A modified water test assessing maximum swallowing volume is recommended to uncover oropharyngeal dysphagia in PD. PD-specific questionnaires may also be useful to identify patients at risk for swallowing impairment. Fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study are both considered to be the gold standard for evaluation of PD-related dysphagia. In addition, high-resolution manometry may be a helpful tool. These instrumental methods allow a reliable detection of aspiration events. Furthermore, typical patterns of impairment during the oral, pharyngeal and/or esophageal swallowing phase of PD patients can be identified. Therapy of dysphagia in PD consists of pharmacological interventions and swallowing treatment by speech and language therapists (SLTs). Fluctuating dysphagia with deterioration during the off-state should be treated by optimizing dopaminergic medication. The methods used during swallowing treatment by SLTs shall be selected according to the individual dysphagia pattern of each PD patient. A promising novel method is an intensive training of expiratory muscle strength. Deep brain stimulation does not seem to have a clinical relevant effect on swallowing function in PD. The goal of this review is giving an overview on current stages of epidemiology, pathophysiology, diagnosis, and treatment of PD-associated dysphagia, which might be helpful for neurologists, speech-language therapists, and other clinicians in their daily work with PD patients and associated swallowing difficulties. Furthermore areas with an urgent need for future clinical research are identified.
10.1007/s00455-015-9671-9
Epidemiology of Parkinson's disease.
de Lau Lonneke M L,Breteler Monique M B
The Lancet. Neurology
The causes of Parkinson's disease (PD), the second most common neurodegenerative disorder, are still largely unknown. Current thinking is that major gene mutations cause only a small proportion of all cases and that in most cases, non-genetic factors play a part, probably in interaction with susceptibility genes. Numerous epidemiological studies have been done to identify such non-genetic risk factors, but most were small and methodologically limited. Larger, well-designed prospective cohort studies have only recently reached a stage at which they have enough incident patients and person-years of follow-up to investigate possible risk factors and their interactions. In this article, we review what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies.
10.1016/S1474-4422(06)70471-9
The diagnosis of Parkinson's disease.
Tolosa Eduardo,Wenning Gregor,Poewe Werner
The Lancet. Neurology
The correct diagnosis of Parkinson's disease is important for prognostic and therapeutic reasons and is essential for clinical research. Investigations of the diagnostic accuracy for the disease and other forms of parkinsonism in community-based samples of patients taking antiparkinsonian medication confirmed a diagnosis of parkinsonism in only 74% of patients and clinically probable Parkinson's disease in 53% of patients. Clinicopathological studies based on brain bank material from the UK and Canada have shown that clinicians diagnose the disease incorrectly in about 25% of patients. In these studies, the most common reasons for misdiagnosis were presence of essential tremor, vascular parkinsonism, and atypical parkinsonian syndromes. Infrequent diagnostic errors included Alzheimer's disease, dementia with Lewy bodies, and drug-induced parkinsonism. Increasing knowledge of the heterogeneous clinical presentation of the various parkinsonisms has resulted in improved diagnostic accuracy of the various parkinsonian syndromes in specialised movement-disorder units. Also genetic testing and various other ancillary tests, such as olfactory testing, MRI, and dopamine-transporter single-photon-emission computed-tomography imaging, help with clinical diagnostic decisions.
10.1016/S1474-4422(05)70285-4
Current trends in etiology, prognosis and therapeutic aspects of Parkinson's disease: a review.
Acta bio-medica : Atenei Parmensis
Parkinson's disease (PD) is a movement disorder, mainly affecting population consisting of the aged. PD occurs chiefly due to progressive loss of dopaminergic neurons in nigrostriatal pathway. Largely, PD patients suffer from non-motor symptoms, such as depression, anxiety, fatigue, and sleep disorders, that needs further investigation and addressing during PD research. Depression in PD is a predominant and complex symptom, and its pathology exists extrinsic to the nigrostriatal system. This disease can ultimately be managed by a combination of regular physiotherapy and proper medication. Taking together the present scenario of PD, including the nature of disease, characteristics, treatment, diagnosis of the patients with PD, these outcomes were reviewed to be explored along with many speech-based solutions to PD in this study. This neurodegenerative disorder needs advancement in research and development which can help patients with PD to lead a normal life.
10.23750/abm.v88i3.6063
Parkinson's disease.
Samii Ali,Nutt John G,Ransom Bruce R
Lancet (London, England)
Parkinson's disease is the most common serious movement disorder in the world, affecting about 1% of adults older than 60 years. The disease is attributed to selective loss of neurons in the substantia nigra, and its cause is enigmatic in most individuals. Symptoms of Parkinson's disease respond in varying degrees to drugs, and surgery offers hope for patients no longer adequately controlled in this manner. The high prevalence of the disease, and important advances in its management, mean that generalists need to have a working knowledge of this disorder. This Seminar covers the basics, from terminology to aspects of diagnosis, treatment, and pathogenesis.
10.1016/S0140-6736(04)16305-8
Parkinson's Disease: Risk Factor Modification and Prevention.
Seminars in neurology
The global burden of Parkinson's disease (PD) has increased from 2.5 to 6.1 million since the 1990s. This is expected to rise as the world population ages and lives longer. With the current consensus on the existence of a of PD, which can be divided into a e and a , we can better define the risk markers and prodromal markers of PD in the broader context of PD pathogenesis. Here, we review this pathogenetic process, and discuss the evidence behind various heritability factors, exposure to pesticides and farming, high dairy consumption, and traumatic brain injuries that have been known to raise PD risk. Physical activity, early active lifestyle, high serum uric acid, caffeine consumption, exposure to tobacco, nonsteroidal anti-inflammatory drugs, and calcium channel blockers, as well as the Mediterranean and the MIND diets are observed to lower PD risk. This knowledge, when combined with ways to identify at-risk populations and early prodromal PD patients, can help the clinician make practical recommendations. Most importantly, it helps us set the parameters for epidemiological studies and create the paradigms for clinical trials.
10.1055/s-0042-1758780
The Genetics of Parkinson's Disease and Implications for Clinical Practice.
Day Jacob Oliver,Mullin Stephen
Genes
The genetic landscape of Parkinson's disease (PD) is characterised by rare high penetrance pathogenic variants causing familial disease, genetic risk factor variants driving PD risk in a significant minority in PD cases and high frequency, low penetrance variants, which contribute a small increase of the risk of developing sporadic PD. This knowledge has the potential to have a major impact in the clinical care of people with PD. We summarise these genetic influences and discuss the implications for therapeutics and clinical trial design.
10.3390/genes12071006
Mitochondria and Parkinson's Disease: Clinical, Molecular, and Translational Aspects.
Borsche Max,Pereira Sandro L,Klein Christine,Grünewald Anne
Journal of Parkinson's disease
Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson's disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction to the disease. Here, proteins encoded by the autosomal recessively inherited PD genes Parkin, PTEN-induced kinase 1 (PINK1), and DJ-1 are involved in mitochondrial pathways. Additional evidence for mitochondrial dysfunction stems from models of autosomal-dominant PD due to mutations in alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2). Moreover, patients harboring alterations in mitochondrial polymerase gamma (POLG) often exhibit signs of parkinsonism. While some molecular studies suggest that mitochondrial dysfunction is a primary event in PD, others speculate that it is the result of impaired mitochondrial clearance. Most recent research even implicated damage-associated molecular patterns released from non-degraded mitochondria in neuroinflammatory processes in PD. Here, we summarize the manifold literature dealing with mitochondria in the context of PD. Moreover, in light of recent advances in the field of personalized medicine, patient stratification according to the degree of mitochondrial impairment followed by mitochondrial enhancement therapy may hold potential for at least a subset of genetic and idiopathic PD cases. Thus, in the second part of this review, we discuss therapeutic approaches targeting mitochondrial dysfunction with the aim to prevent or delay neurodegeneration in PD.
10.3233/JPD-201981
Progress towards therapies for disease modification in Parkinson's disease.
The Lancet. Neurology
The development of interventions to slow or halt the progression of Parkinson's disease remains a priority for patients and researchers alike. To date, no agents have been shown to have unequivocal evidence of disease-modifying effects in Parkinson's disease. The absence of disease-modifying treatments might relate not only to inadequate approaches for the selection of therapeutic candidates but also to insufficient attention to detail in clinical trial design. Better understanding of Parkinson's disease pathogenesis associated with advances in laboratory models, the use of objective biomarkers of disease progression and target engagement, and a focus on agents known to be safe for human use, alongside the use of precision medicine approaches, should together greatly increase the likelihood for successful identification of disease-modifying treatments for Parkinson's disease.
10.1016/S1474-4422(21)00061-2
Motor assessment in Parkinson`s disease.
Opara Józef,Małecki Andrzej,Małecka Elżbieta,Socha Teresa
Annals of agricultural and environmental medicine : AAEM
Parkinson's disease (PD) is one of most disabling disorders of the central nervous system. The motor symptoms of Parkinson's disease: shaking, rigidity, slowness of movement, postural instability and difficulty with walking and gait, are difficult to measure. When disease symptoms become more pronounced, the patient experiences difficulties with hand function and walking, and is prone to falls. Baseline motor impairment and cognitive impairment are probable predictors of more rapid motor decline and disability. An additional difficulty is the variability of the symptoms caused by adverse effects of drugs, especially levodopa. Motor assessment of Parkinson`s Disease can be divided into clinimetrics, assessment of balance and posture, arm and hand function, and gait/walking. These are many clinimetric scales used in Parkinson`s Disease, the most popular being the Hoehn and Yahr stages of progression of the disease and Unified Parkinson's Disease Rating Scale. Balance and posture can be assessed by clinimetric scales like the Berg BS, Tinetti, Brunel BA, and Timed Up and Go Test, or measured by posturometric platforms. Among skill tests, the best known are: the Purdue Pegboard Test, Nine-Hole Peg Test, Jebsen and Taylor test, Pig- Tail Test, Frenchay Arm Test, Action Research Arm Test, Wolf FMT and Finger-Tapping Test. Among motricity scales, the most popular are: the Fugl-Meyer Motor Assessment Scale and Södring Motor Evaluation. Gait and walking can also be assessed quantitatively and qualitatively. Recently, the most popular is three-dimensional analysis of movement. This review article presents the current possibilities of motor assessment in Parkinson`s disease.
10.5604/12321966.1232774
Parkinson's disease: Mechanisms, translational models and management strategies.
Raza Chand,Anjum Rabia,Shakeel Noor Ul Ain
Life sciences
Parkinson's disease is a progressive neurodegenerative disorder. The classical motor symptoms include resting tremors, bradykinesia, rigidity and postural instability and are accompanied by the loss of dopaminergic neurons and Lewy pathology. Diminished neurotransmitter level, oxidative stress, mitochondrial dysfunction and perturbed protein homeostasis over time worsen the disease manifestations in elderly people. Current management strategies aim to provide symptomatic relief and to slow down the disease progression. However, no pharmacological breakthrough has been made to protect dopaminergic neurons and associated motor circuitry components. Deep brain stimulation, stem cells-derived dopaminergic neurons transplantation, gene editing and gene transfer remain promising approaches for the potential management of neurodegenerative disease. Toxin or genetically induced rodent models replicating Parkinson's disease pathology are of high predictive value for translational research. This review addresses the current understanding, management strategies and the Parkinson's disease models for translational research. Preclinical research may provide powerful tools to quest the potential therapeutic and neuroprotective compounds for dopaminergic neurons and hence possible cure for the Parkinson's disease.
10.1016/j.lfs.2019.03.057
Biomarkers for Parkinson's Disease: Recent Advancement.
Neuroscience bulletin
As a multi-factorial degenerative disease, Parkinson's disease (PD) leads to tremor, gait rigidity, and hypokinesia, thus hampering normal living. As this disease is usually detected in the later stages when neurons have degenerated completely, cure is on hold, ultimately leading to death due to the lack of early diagnostic techniques. Thus, biomarkers are required to detect the disease in the early stages when prevention is possible. Various biomarkers providing early diagnosis of the disease include those of imaging, cerebrospinal fluid, oxidative stress, neuroprotection, and inflammation. Also, biomarkers, alone or in combination, are used in the diagnosis and evolution of PD. This review encompasses various biomarkers available for PD and discusses recent advances in their development.
10.1007/s12264-017-0183-5
Autonomic dysfunction in Parkinson's disease: Implications for pathophysiology, diagnosis, and treatment.
Chen Zhichun,Li Guanglu,Liu Jun
Neurobiology of disease
Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains limited, although dopaminergic replacement therapy has significantly improved patient outcomes. Autonomic dysfunction is an essential category of non-motor phenotypes that has recently become a cutting edge field that directs frontier research in PD. In this review, we initially describe the epidemiology of dysautonomic symptoms in PD. Then, we perform a meticulous analysis of the pathophysiology of autonomic dysfunction in PD and propose that the peripheral autonomic nervous system may be a key route for α-synuclein pathology propagation from the periphery to the central nervous system. In addition, we recommend that constipation, orthostatic hypotension, urinary dysfunction, erectile dysfunction, and pure autonomic failure should be viewed as prodromal dysautonomic markers in PD prediction and diagnosis. Finally, we summarize the strategies currently available for the treatment of autonomic dysfunction in PD and suggest that high-quality, better-designed, randomized clinical trials should be conducted in the future.
10.1016/j.nbd.2019.104700
Diagnosis, treatment and management of apathy in Parkinson's disease: a scoping review.
BMJ open
OBJECTIVE:To conduct a scoping review of the literature on apathy in Parkinson's disease (PD), to better understand how apathy in Parkinson's disease is diagnosed, treated and managed. METHODS:MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central Register of Control Trials and Cochrane Database of Systematic Reviews were searched to 17 May 2017. An updated review was run from 17 May 2017 to 28 January 2019. The grey literature was searched using the CADTH Grey Matters tool. Original peer-reviewed research was included if it included individuals with PD and apathy. Non-original data was only included if it was in the form of meta-analysis. All information regarding diagnosis, treatment and management of PD was extracted. Citation screening and extraction were performed in duplicate. RESULTS:From 11 375 citations, 362 articles were included in the final review. The majority of included studies focussed on prevalence, with few studies examining treatment. Twenty screening tools for apathy were identified. Fifty per cent of treatment studies were randomised control trials (RCTs). RCTs applied treatment methods including: exercise, mindfulness, rotigotine (Neupro) transdermal patch and rivastigmine (Exelon). CONCLUSIONS:This review identified a large body of literature describing current knowledge on diagnosing, treating and managing apathy in PD. Future research should aim to detect an ideal screening tool for apathy in PD, to identify the best treatment options for apathy and the variety of comorbidities it may present with and finally aim to better understand postoperative apathy in those with deep brain stimulation.
10.1136/bmjopen-2020-037632
The epidemiology of Parkinson's disease: risk factors and prevention.
Ascherio Alberto,Schwarzschild Michael A
The Lancet. Neurology
Since 2006, several longitudinal studies have assessed environmental or behavioural factors that seem to modify the risk of developing Parkinson's disease. Increased risk of Parkinson's disease has been associated with exposure to pesticides, consumption of dairy products, history of melanoma, and traumatic brain injury, whereas a reduced risk has been reported in association with smoking, caffeine consumption, higher serum urate concentrations, physical activity, and use of ibuprofen and other common medications. Randomised trials are investigating the possibility that some of the negative risk factors might be neuroprotective and thus beneficial in individuals with early Parkinson's disease, particularly with respect to smoking (nicotine), caffeine, and urate. In the future, it might be possible to identify Parkinson's disease in its prodromal phase and to promote neuroprotective interventions before the onset of motor symptoms. At this time, however, the only intervention that seems justifiable for the primary prevention of Parkinson's disease is the promotion of physical activity, which is likely to be beneficial for the prevention of several chronic diseases.
10.1016/S1474-4422(16)30230-7
Parkinson's disease: etiopathogenesis and treatment.
Jankovic Joseph,Tan Eng King
Journal of neurology, neurosurgery, and psychiatry
The concept of 'idiopathic' Parkinson's disease (PD) as a single entity has been challenged with the identification of several clinical subtypes, pathogenic genes and putative causative environmental agents. In addition to classic motor symptoms, non-motor manifestations (such as rapid eye movement sleep disorder, anosmia, constipation and depression) appear at prodromic/premotor stage and evolve, along with cognitive impairment and dysautonomia, as the disease progresses, often dominating the advanced stages of the disease. The key molecular pathogenic mechanisms include α-synuclein misfolding and aggregation, mitochondrial dysfunction, impairment of protein clearance (associated with deficient ubiquitin-proteasome and autophagy-lysosomal systems), neuroinflammation and oxidative stress. The involvement of dopaminergic as well as noradrenergic, glutamatergic, serotonergic and adenosine pathways provide insights into the rich and variable clinical phenomenology associated with PD and the possibility of alternative therapeutic approaches beyond traditional dopamine replacement therapies.One of the biggest challenges in the development of potential neuroprotective therapies has been the lack of reliable and sensitive biomarkers of progression. Immunotherapies such as the use of vaccination or monoclonal antibodies directed against aggregated, toxic α-synuclein.as well as anti-aggregation or protein clearance strategies are currently investigated in clinical trials. The application of glucagon-like peptide one receptor agonists, specific PD gene target agents (such as GBA or LRRK2 modifiers) and other potential disease modifying drugs provide cautious optimism that more effective therapies are on the horizon. Emerging therapies, such as new symptomatic drugs, innovative drug delivery systems and novel surgical interventions give hope to patients with PD about their future outcomes and prognosis.
10.1136/jnnp-2019-322338
Parkinson's Disease in Women and Men: What's the Difference?
Cerri Silvia,Mus Liudmila,Blandini Fabio
Journal of Parkinson's disease
Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson's disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.
10.3233/JPD-191683
Epidemiology of Parkinson's disease.
Tysnes Ole-Bjørn,Storstein Anette
Journal of neural transmission (Vienna, Austria : 1996)
Parkinson's disease (PD) affects 1-2 per 1000 of the population at any time. PD prevalence is increasing with age and PD affects 1% of the population above 60 years. The main neuropathological finding is α-synuclein-containing Lewy bodies and loss of dopaminergic neurons in the substantia nigra, manifesting as reduced facilitation of voluntary movements. With progression of PD, Lewy body pathology spreads to neocortical and cortical regions. PD is regarded as a movement disorder with three cardinal signs: tremor, rigidity and bradykinesia. A recent revision of the diagnostic criteria excludes postural instability as a fourth hallmark and defines supportive criteria, absolute exclusion criteria and red flags. Non-motor symptoms in PD have gained increasing attention and both motor and non-motor signs are now included among the supportive criteria. The cause of PD is unknown in most cases. Genetic risk factors have been identified, including monogenetic causes that are rare in unselected populations. Some genetic factor can be identified in 5-10% of the patients. Several environmental factors are associated with increased risk of PD. Autopsy studies show that the clinical diagnosis of PD is not confirmed at autopsy in a significant proportion of patients. Revised diagnostic criteria are expected to improve the clinician´s accuracy in diagnosing PD. Increasing knowledge on genetic and environmental risk factors of PD will probably elucidate the cause of this disease within the near future.
10.1007/s00702-017-1686-y
Parkinson's Disease.
Reich Stephen G,Savitt Joseph M
The Medical clinics of North America
The diagnosis of Parkinson disease (PD) is based on the presence of bradykinesia and either resting tremor or rigidity and there should be no features from the history or examination to suggest an alternative cause of parkinsonism. In addition to the motor manifestations of PD, there is a long list of nonmotor symptoms, several of which occur before motor signs and are considered "prodromal" PD. These are classified as neuropsychiatric, autonomic, sleep, and sensory. There are many medical options for the treatment of PD but levodopa remains the mainstay. Deep brain stimulation and other advanced therapies are also available.
10.1016/j.mcna.2018.10.014
Parkinson's disease.
Kalia Lorraine V,Lang Anthony E
Lancet (London, England)
Parkinson's disease is a neurological disorder with evolving layers of complexity. It has long been characterised by the classical motor features of parkinsonism associated with Lewy bodies and loss of dopaminergic neurons in the substantia nigra. However, the symptomatology of Parkinson's disease is now recognised as heterogeneous, with clinically significant non-motor features. Similarly, its pathology involves extensive regions of the nervous system, various neurotransmitters, and protein aggregates other than just Lewy bodies. The cause of Parkinson's disease remains unknown, but risk of developing Parkinson's disease is no longer viewed as primarily due to environmental factors. Instead, Parkinson's disease seems to result from a complicated interplay of genetic and environmental factors affecting numerous fundamental cellular processes. The complexity of Parkinson's disease is accompanied by clinical challenges, including an inability to make a definitive diagnosis at the earliest stages of the disease and difficulties in the management of symptoms at later stages. Furthermore, there are no treatments that slow the neurodegenerative process. In this Seminar, we review these complexities and challenges of Parkinson's disease.
10.1016/S0140-6736(14)61393-3
Parkinson's Disease and Parkinsonism.
Hayes Michael T
The American journal of medicine
Parkinson's disease is a progressive neurodegenerative disease characterized by tremor and bradykinesia and is a common neurologic ailment. Male sex and advancing age are independent risk factors and, as the population ages, is taking an increasing toll on productivity and medical resources. There are a number of other extrapyramidal conditions that can make the diagnosis challenging. Unlike other neurodegenerative diseases, idiopathic Parkinson's disease has effective treatments that mitigate symptoms. Medications can improve day-to-day function and, in cases where medication does not give a sustained benefit or has significant side effects, treatments like deep brain stimulation result in improved quality of life.
10.1016/j.amjmed.2019.03.001
Parkinson's disease: a review.
Beitz Janice M
Frontiers in bioscience (Scholar edition)
Parkinson's Disease is the second most common progressive neurodegenerative disorder affecting older American adults and is predicted to increase in prevalence as the United States population ages. Resulting from a pathophysiologic loss or degeneration of dopaminergic neurons in the substantia nigra of the midbrain and the development of neuronal Lewy Bodies, idiopathic Parkinson's Disease is associated with risk factors including aging, family history, pesticide exposure and environmental chemicals (e.g., synthetic heroin use). Its ultimate cause(s) is (are) unknown. Characterized by both motor and non-motor symptoms, PD patients classically display rest tremor, rigidity, bradykinesia, and stooping posture. PD can also be associated with neurobehavioral disorders (depression, anxiety), cognitive impairment (dementia), and autonomic dysfunction (e.g., orthostasis and hyperhidrosis). Recent decades have witnessed a proliferation of medical pharmacologic therapies and innovative surgical interventions like deep brain stimulation (DBS). However, definitive disease-modifying therapy is still lacking. Experimental therapies are being developed and tested with limited results. Knowledge of strategies to promote optimal quality of life for PD patients is of paramount importance for caregivers, health providers and patients themselves.
10.2741/s415
[Parkinson's Disease: Clinical Review and Update].
Cabreira Verónica,Massano João
Acta medica portuguesa
Parkinson's disease is the second most common neurodegenerative disorder, and a significant increase in its prevalence in the past three decades has been documented. Environmental and genetic factors contribute to the pathophysiology of this disease, and 5% - 10% of cases have a monogenic cause. The diagnosis relies on clinical findings, supported by adequate testing. There is no absolute method to diagnose Parkinson's disease in vivo, except for genetic testing in specific circumstances, whose usefulness is limited to a minority of cases. New diagnostic criteria have been recently proposed with the aim of improving diagnostic accuracy, emphasizing findings that might point to other causes of parkinsonism. The available therapeutic options are clinically useful, as they improve the symptoms as well as the quality of life of patients. After the introduction of levodopa, deep brain stimulation emerged as the second therapy with an important symptomatic impact in the treatment of Parkinson's disease. Non-motor symptoms and motor complications are responsible for a large proportion of disability, so these should be identified and treated. Current scientific research is focused on the identification of disease biomarkers allowing correct and timely diagnosis, and on creating more effective therapies, thus fulfilling current clinical unmet needs. This paper presents an updated review on Parkinson's disease, guiding the readership through current concepts, and allowing their application to daily clinical practice.
10.20344/amp.11978
Challenges in the diagnosis of Parkinson's disease.
The Lancet. Neurology
Parkinson's disease is the second most common neurodegenerative disease and its prevalence has been projected to double over the next 30 years. An accurate diagnosis of Parkinson's disease remains challenging and the characterisation of the earliest stages of the disease is ongoing. Recent developments over the past 5 years include the validation of clinical diagnostic criteria, the introduction and testing of research criteria for prodromal Parkinson's disease, and the identification of genetic subtypes and a growing number of genetic variants associated with risk of Parkinson's disease. Substantial progress has been made in the development of diagnostic biomarkers, and genetic and imaging tests are already part of routine protocols in clinical practice, while novel tissue and fluid markers are under investigation. Parkinson's disease is evolving from a clinical to a biomarker-supported diagnostic entity, for which earlier identification is possible, different subtypes with diverse prognosis are recognised, and novel disease-modifying treatments are in development.
10.1016/S1474-4422(21)00030-2