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    Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Maldonado José R The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Delirium is a neurobehavioral syndrome caused by dysregulation of neuronal activity secondary to systemic disturbances. Over time, a number of theories have been proposed in an attempt to explain the processes leading to the development of delirium. Each proposed theory has focused on a specific mechanism or pathologic process (e.g., dopamine excess or acetylcholine deficiency theories), observational and experiential evidence (e.g., sleep deprivation, aging), or empirical data (e.g., specific pharmacologic agents' association with postoperative delirium, intraoperative hypoxia). This article represents a review of published literature and summarizes the top seven proposed theories and their interrelation. This review includes the "neuroinflammatory," "neuronal aging," "oxidative stress," "neurotransmitter deficiency," "neuroendocrine," "diurnal dysregulation," and "network disconnectivity" hypotheses. Most of these theories are complementary, rather than competing, with many areas of intersection and reciprocal influence. The literature suggests that many factors or mechanisms included in these theories lead to a final common outcome associated with an alteration in neurotransmitter synthesis, function, and/or availability that mediates the complex behavioral and cognitive changes observed in delirium. In general, the most commonly described neurotransmitter changes associated with delirium include deficiencies in acetylcholine and/or melatonin availability; excess in dopamine, norepinephrine, and/or glutamate release; and variable alterations (e.g., either a decreased or increased activity, depending on delirium presentation and cause) in serotonin, histamine, and/or γ-aminobutyric acid. In the end, it is unlikely that any one of these theories is fully capable of explaining the etiology or phenomenologic manifestations of delirium but rather that two or more of these, if not all, act together to lead to the biochemical derangement and, ultimately, to the complex cognitive and behavioral changes characteristic of delirium. 10.1016/j.jagp.2013.09.005
    MRI Markers of Neurodegenerative and Neurovascular Changes in Relation to Postoperative Delirium and Postoperative Cognitive Decline. Kant Ilse M J,de Bresser Jeroen,van Montfort Simone J T,Slooter Arjen J C,Hendrikse Jeroen The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Postoperative delirium (POD) and postoperative cognitive decline (POCD) are common in elderly patients. The aim of the present review was to explore the association of neurodegenerative and neurovascular changes with the occurrence of POD and POCD. Fifteen MRI studies were identified by combining multiple search terms for POD, POCD, and brain imaging. These studies described a total of 1,422 patients and were all observational in design. Neurodegenerative changes (global and regional brain volumes) did not show a consistent association with the occurrence of POD (four studies) or POCD (two studies). In contrast, neurovascular changes (white matter hyperintensities and cerebral infarcts) were more consistently associated with the occurrence of POD (seven studies) and POCD (five studies). In conclusion, neurovascular changes appear to be consistently associated with the occurrence of POD and POCD, and may identify patients at increased risk of these conditions. Larger prospective studies are needed to study the consistency of these findings and to unravel the underlying pathophysiological mechanisms. 10.1016/j.jagp.2017.06.016
    Depressive Symptoms and Risk of Postoperative Delirium. Smith Patrick J,Attix Deborah K,Weldon B Craig,Monk Terri G The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry OBJECTIVE:Previous studies have shown that elevated depressive symptoms are associated with increased risk of postoperative delirium. However, to our knowledge no previous studies have examined whether different components of depression are differentially predictive of postoperative delirium. METHODS:One thousand twenty patients were screened for postoperative delirium using the Confusion Assessment Method and through retrospective chart review. Patients underwent cognitive, psychosocial, and medical assessments preoperatively. Depression was assessed using the Geriatric Depression Scale-Short Form. RESULTS:Thirty-eight patients developed delirium (3.7%). Using a factor structure previously validated among geriatric medical patients, the authors examined three components of depression as predictors of postoperative delirium: negative affect, cognitive distress, and behavioral inactivity. In multivariate analyses controlling for age, education, comorbidities, and cognitive function, the authors found that greater behavioral inactivity was associated with increased risk of delirium (OR: 1.95 [1.11, 3.42]), whereas negative affect (OR: 0.65 [0.31, 1.36]) and cognitive distress (OR: 0.95 [0.63, 1.43]) were not. CONCLUSION:Different components of depression are differentially predictive of postoperative delirium among adults undergoing noncardiac surgery. 10.1016/j.jagp.2015.12.004
    Delirium Subtypes and Associated Characteristics in Older Patients With Exacerbation of Chronic Conditions. Gual Neus,Inzitari Marco,Carrizo Gabriela,Calle Alicia,Udina Cristina,Yuste Anna,Morandi Alessandro The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry OBJECTIVE:The prevalence and prognosis of delirium motor subtypes are not yet well established. We analyzed the prevalence of motor subtypes of delirium, as well as their risk factors and outcomes, among older vulnerable patients admitted for short-term management of exacerbated chronic conditions. METHODS:Cohort study of patients aged 65 and older who developed delirium while admitted to a subacute care unit for 12 months (N = 352). Confusion Assessment Method was used to determine the presence of delirium and the Delirium Motor Subtype Scale was used to define the motor subtype. Outcomes included discharge destination, mortality, readmission, and functional trajectories. RESULTS:Out of 352 patients with delirium (mean age= 87.4, 73.6% with dementia), hyperactive delirium was the most prevalent subtype (40.6%), followed by mixed (31%), hypoactive (25.9%), and nonmotor (2.6%). In multivariate models, worse preadmission functional status (odds ratio [OR] [95% confidence interval {CI}] = 0.97 [0.96-0.98]) and higher comorbidity (OR [95% CI] = 1.3 [1.04-1.51]) were associated with an increased risk of hypoactive delirium. In multivariate models adjusted for different variables, including disability, hypoactive delirium was associated with mortality compared with hyperactive delirium (OR [95% CI] = 4.7 [1.6-14]) and mixed delirium (OR [95% CI] = 2.0 [1.02-3.9]) and with worse functional recovery (Beta[95% CI] = -0.2 [-12.0-(-0.4)]). CONCLUSION:Delirium motor subtypes were associated with different patient characteristics and outcomes. Hypoactive delirium seems to affect more vulnerable patients and to be associated with worse outcomes. More research on the different delirium subtypes could help develop better preventive and management strategies. 10.1016/j.jagp.2018.07.003
    Clinical Features Associated with Delirium Motor Subtypes in Older Inpatients: Results of a Multicenter Study. Morandi Alessandro,Di Santo Simona G,Cherubini Antonio,Mossello Enrico,Meagher David,Mazzone Andrea,Bianchetti Angelo,Ferrara Nicola,Ferrari Alberto,Musicco Massimo,Trabucchi Marco,Bellelli Giuseppe, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry OBJECTIVE:To date motor subtypes of delirium have been evaluated in single-center studies with a limited examination of the relationship between predisposing factors and motor profile of delirium. We sought to report the prevalence and clinical profile of subtypes of delirium in a multicenter study. METHODS:This is a point prevalence study nested in the "Delirium Day 2015", which included 108 acute and 12 rehabilitation wards in Italy. Delirium was detected using the 4-AT and motor subtypes were measured with the Delirium Motor Subtype Scale (DMSS). A multinomial logistic regression was used to determine the factors associated with delirium subtypes. RESULTS:Of 429 patients with delirium, the DMSS was completed in 275 (64%), classifying 21.5% of the patients with hyperactive delirium, 38.5% with hypoactive, 27.3% with mixed and 12.7% with the non-motor subtype. The 4-AT score was higher in the hyperactive subtype, similar in the hypoactive, mixed subtypes, while it was lowest in the non-motor subtype. Dementia was associated with all three delirium motor subtypes (hyperactive, OR 3.3, 95% CI: 1.2-8.7; hypoactive, OR 2.8, 95% CI: 1.2-6.5; mixed OR 2.6, 95% CI: 1.1-6.2). Atypical antipsychotics were associated with hypoactive delirium (OR 0.23, 95% CI: 0.1-0.7), while intravenous lines were associated with mixed delirium (OR 2.9, 95% CI: 1.2-6.9). CONCLUSIONS:The study shows that hypoactive delirium is the most common subtype among hospitalized older patients. Specific clinical features were associated with different delirium subtypes. The use of standardized instruments can help to characterize the phenomenology of different motor subtypes of delirium. 10.1016/j.jagp.2017.05.003
    Delirium: Medical Students' Knowledge and Effectiveness of Different Teaching Methods. Baessler Franziska,Ciprianidis Anja,Rizvi Ali Z,Weidlich Joshua,Wagner Fabienne L,Klein Sonja B,Baumann Tabea C,Nikendei Christoph,Schultz Jobst-Hendrik The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry OBJECTIVE:Medical schools are often blamed for inadequately training doctors on delirium. This study assesses the knowledge of medical students regarding delirium and evaluates different teaching methods for comparing learning outcomes. METHODS:A video, a handout, and a video+handout were used as three different teaching methods. Students were randomly assigned to three groups and pre- and postintervention knowledge gains were compared. Interventions were held between 2015 and 2018 at the University of Heidelberg Medical School in Germany. Seventy-eight (video intervention 33; handout 26; video+handout 19) sixth-year medical students participated. Participants learned about delirium with the help of a video, a handout, and both a video+handout at the start of one-hour lectures dedicated to teaching about delirium. Pre- and postintervention questionnaires, comprising five multiple-choice questions and a self-estimated grade of knowledge about delirium, were used. Variables calculated were objective and subjective knowledge, recall, and accuracy of self-assessment. Microsoft Excel and analysis of covariance were used to analyze data. RESULTS:Knowledge gains for all interventions were large (d>0.8) irrespective of gender. Post hoc comparison showed video and video+handout methods were more effective with high recall for video (92.8%). Students rated their knowledge as satisfactory, although they scored 11.4 out of 20. Preintervention knowledge level was correctly estimated by 31% of students, and postintervention by 40.3% students. CONCLUSION:Teaching about delirium to medical students with a video resulted in better knowledge transfer and recall. Most medical students, particularly men, overestimated their knowledge about delirium. 10.1016/j.jagp.2019.03.003