Impact of Obstructive Sleep Apnea on Neurocognitive Function and Impact of Continuous Positive Air Pressure. Davies Charles R,Harrington John J Sleep medicine clinics There is evidence that obstructive sleep apnea (OSA) can negatively impact attention, memory, learning, executive function, and overall intellectual function in adults and children. Imaging techniques, including MRI, MR diffusion tensor imaging, MR spectroscopy, and fMRI, have provided additional insight into the anatomic and functional underpinnings of OSA-related cognitive impairment. Both animal and human studies have looked to elucidate the separate effects of oxygen desaturation and sleep fragmentation on independent aspects of cognition. Data from animal models point to neuro-inflammation and oxidative stress as driving factors of cognitive impairment. 10.1016/j.jsmc.2016.04.006
    Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome. Busch David R,Lynch Jennifer M,Winters Madeline E,McCarthy Ann L,Newland John J,Ko Tiffany,Cornaglia Mary Anne,Radcliffe Jerilynn,McDonough Joseph M,Samuel John,Matthews Edward,Xiao Rui,Yodh Arjun G,Marcus Carole L,Licht Daniel J,Tapia Ignacio E Sleep STUDY OBJECTIVES:Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. METHODS:CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. RESULTS:Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). CONCLUSIONS:Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS. 10.5665/sleep.5350
    Obstructive sleep apnea. White David P,Younes Magdy K Comprehensive Physiology Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive collapse of the pharyngeal airway during sleep. Control of pharyngeal patency is a complex process relating primarily to basic anatomy and the activity of many pharyngeal dilator muscles. The control of these muscles is regulated by a number of processes including respiratory drive, negative pressure reflexes, and state (sleep) effects. In general, patients with OSA have an anatomically small airway the patency of which is maintained during wakefulness by reflex-driven augmented dilator muscle activation. At sleep onset, muscle activity falls, thereby compromising the upper airway. However, recent data suggest that the mechanism of OSA differs substantially among patients, with variable contributions from several physiologic characteristics including, among others: level of upper airway dilator muscle activation required to open the airway, increase in chemical drive required to recruit the pharyngeal muscles, chemical control loop gain, and arousal threshold. Thus, the cause of sleep apnea likely varies substantially between patients. Other physiologic mechanisms likely contributing to OSA pathogenesis include falling lung volume during sleep, shifts in blood volume from peripheral tissues to the neck, and airway edema. Apnea severity may progress over time, likely due to weight gain, muscle/nerve injury, aging effects on airway anatomy/collapsibility, and changes in ventilatory control stability. 10.1002/cphy.c110064
    Palatal implant system can provide effective treatment for obstructive sleep apnea by recovering retropalatal patency. Seo Jungmin,Yun Seunghyeon,Shim Shinyong,Cho Sung-Woo,Choi Jin-Woo,Kim Jeong-Whun,Kim Sung June Journal of neural engineering OBJECTIVE:Obstructive sleep apnea (OSA) is a disorder with a high prevalence rate that may induce serious complications. Recent progress in the area of hypoglossal nerve stimulation has played a role as an alternative to conventional therapies though, some patients having retropalatal collapse still have not benefitted. Therefore, here we propose a new type of upper-airway stimulation, referred to as the palatal implant system, which recovers the upper-airway patency by electrically stimulating the soft palate. APPROACH:The system consists of two major parts: an implant that stimulates the soft palate through electrodes and an intra-oral device that delivers power and data simultaneously to the implant via an inductive link. Evaluations of the system are conducted in bench-top, in vitro, and in vivo tests to evaluate its feasibility as an OSA treatment, and the potential development of the system is addressed in the discussion section. MAIN RESULTS:In the bench-top test, the power efficiency was 12.4% at d = 5 mm and the system could operate up to 8 mm distance in a bio-medium. Data transmission was also successful at distances ranging 2 to 8 mm within an error margin of 10%. The measured CSC and the impedance magnitude of the electrode were 62.25 mC cm and 390 Ω, respectively, proving a feasibility of the electrode as a stimluator interface. The system was applied to a rabbit and contraction of the soft palate muscle was recorded via a C-arm fluoroscopy. SIGNIFICANCE:As a proof of concept, we suggest and demonstrate the palatal implant system as a new therapy for those undergoing treatment for OSA. 10.1088/1741-2552/ab7d61
    Non-surgical treatment of obstructive sleep apnea syndrome. Tingting Xu,Danming You,Xin Chen European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Obstructive sleep apnea syndrome (OSAS), a pervasive disease, is closely associated with complications such as cardiovascular diseases, neurocognitive diseases, and metabolic syndromes. Continuous positive airway pressure (CPAP) is the standard treatment for OSAS, with low compliance due to multifarious factors. The two other modes of ventilation, bi-level positive airway pressure (BPAP) and autotitrating positive airway pressure (APAP), which were developed from CPAP, are slightly different from CPAP in specific groups, as well as the corresponding treatment effect and compliance. The compliance of traditional positional therapy is not high, but with the emergence of the neck-based position treatment device, its compliance and indications have changed. Although CPAP is superior to mandibular advancement device (MAD) in improving AHI, MAD seems to be comparable to CPAP in improving other indicators. Corticosteroids and leukotriene receptor antagonists are effective treatments for mild OSAS children. Whether corticosteroids can be used in other OSAS groups and their adjunctive functions to CPAP remains unclear. The combination of these two kinds of drugs appears to be more effective than single drug. Researches on transcutaneous electrical stimulation are still not enough. Its effectiveness and stimulation settings still need further study. This review summarized the various OSAS non-surgical treatments from indications, treatment outcomes, compliance, adverse reactions, and recent progress. 10.1007/s00405-017-4818-y
    Obstructive sleep apnoea and dementia: is there a link? Shastri Abhishek,Bangar Santosh,Holmes John International journal of geriatric psychiatry OBJECTIVE:Obstructive sleep apnoea is a common sleep disturbance in people of all ages, while dementia is an increasing entity among the ageing population of the world. Recent studies have established a link between sleep apnoea and cognitive decline. This literature review explores this relationship and examines the mechanisms, neurobiology and treatment modalities. DESIGN:The study was conducted with the use of narrative literature overview. RESULTS AND CONCLUSIONS:While there are numerous studies that establish a clear relationship between obstructive sleep apnoea, cognitive decline and dementia, more work is needed in understanding the mechanism and processes involved. A detailed understanding of pathophysiology of sleep and the relationship with cognitive decline will be vital in addressing the possibility of averting a likely reversible cause of dementia or cognitive decline. 10.1002/gps.4345
    Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Echouffo-Tcheugui Justin B,Conner Sarah C,Himali Jayandra J,Maillard Pauline,DeCarli Charles S,Beiser Alexa S,Vasan Ramachandran S,Seshadri Sudha Neurology OBJECTIVE:To assess the association of early morning serum cortisol with cognitive performance and brain structural integrity in community-dwelling young and middle-aged adults without dementia. METHODS:We evaluated dementia-free Framingham Heart Study (generation 3) participants (mean age 48.5 years, 46.8% men) who underwent cognitive testing for memory, abstract reasoning, visual perception, attention, and executive function (n = 2,231) and brain MRI (n = 2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear and logistic regression to assess the relations of cortisol (categorized in tertiles, with the middle tertile as referent) to measures of cognition, MRI volumes, presence of covert brain infarcts and cerebral microbleeds, and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, , and vascular risk factors. RESULTS:Higher cortisol (highest tertile vs middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain and occipital and frontal lobar gray matter volumes. Higher cortisol was associated with multiple areas of microstructural changes (decreased regional FA), especially in the splenium of corpus callosum and the posterior corona radiata. The association of cortisol with total cerebral brain volume varied by sex ( for interaction = 0.048); higher cortisol was inversely associated with cerebral brain volume in women ( = 0.001) but not in men ( = 0.717). There was no effect modification by the genotype of the relations of cortisol and cognition or imaging traits. CONCLUSION:Higher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic younger to middle-aged adults, with the association being evident particularly in women. 10.1212/WNL.0000000000006549
    The effects of HPA axis function on cognition and its implications for the pathophysiology of bipolar disorder. Young Allan H Harvard review of psychiatry Bipolar disorders (BDs) are common and complex diseases. Recent findings have provided the basis for an integrated approach linking seemingly disparate findings, based on a greater understanding of the effects of stress on those vulnerable to these illnesses and the brain's consequent responses. Genes are associated with this disorder, although their integration into current pathophysiological models is unclear. Manic states are associated with enhanced dopaminergic transmission, and experimental stress enhances dopamine neurotransmission and impairs cognition. Stress activates the hypothalamic-pituitary-adrenal axis, and dysfunction of this axis and impairments in neurocognitive function have both been demonstrated in BD. Glucocorticoid receptors are abnormal in postmortem brain studies in BD and play an important role in the HPA axis. The glucocorticoid receptor antagonist RU-486 has been shown to improve aspects of cognitive function in BD. The implications of these findings for models of pathophysiology are discussed. Future efforts should focus on further integrating the current and emerging research findings into a coherent pathophysiological model that generates testable hypotheses. 10.1097/HRP.0000000000000020
    HPA axis in psychotic major depression and schizophrenia spectrum disorders: Cortisol, clinical symptomatology, and cognition. Cherian Kirsten,Schatzberg Alan F,Keller Jennifer Schizophrenia research The Hypothalamic Pituitary Adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance, and a potential role of HPA axis genetic variation in cognition. In schizophrenia differential HPA activity has been found, including higher rates of non-suppression to dexamethasone challenge and higher salivary cortisol levels, which have been a premonitory risk factor for conversion to psychosis in adolescents at risk for developing schizophrenia. The present study investigated the simultaneous roles HPA axis activity and clinical symptomatology play in poor cognitive performance. Patients with major depression with psychosis (PMD) or schizophrenia spectrum disorder (SCZ) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, and overnight hourly blood sampling for cortisol. Cognitive performance did not differ between the clinical groups, though they both performed more poorly than the HC's across a variety of cognitive domains. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher evening cortisol levels than did SCZ and HCs. Cortisol and clinical symptoms, as well as age, sex, and antipsychotic use predicted cognitive performance. Diathesis stress models and their links to symptomatology, cognition, and HPA function are discussed. 10.1016/j.schres.2019.07.003
    Biomarkers of dementia in obstructive sleep apnea. Baril Andrée-Ann,Carrier Julie,Lafrenière Alexandre,Warby Simon,Poirier Judes,Osorio Ricardo S,Ayas Najib,Dubé Marie-Pierre,Petit Dominique,Gosselin Nadia, Sleep medicine reviews Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decision-making. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimer's disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk. 10.1016/j.smrv.2018.08.001
    Magnetic resonance imaging of obstructive sleep apnea in children. Fleck Robert J,Shott Sally R,Mahmoud Mohamed,Ishman Stacey L,Amin Raouf S,Donnelly Lane F Pediatric radiology Sleep-disordered breathing has a spectrum of severity that spans from snoring and partial airway collapse with increased upper airway resistance, to complete upper airway obstruction with obstructive sleep apnea during sleeping. While snoring occurs in up to 20% of children, obstructive sleep apnea affects approximately 1-5% of children. The obstruction that occurs in obstructive sleep apnea is the result of the airway collapsing during sleep, which causes arousal and impairs restful sleep. Adenotonsillectomy is the first-line treatment of obstructive sleep apnea and is usually effective in otherwise healthy nonsyndromic children. However, there are subgroups in which this surgery is less effective. These subgroups include children with obesity, severe obstructive sleep apnea preoperatively, Down syndrome, craniofacial anomalies and polycystic ovarian disease. Continuous positive airway pressure (CPAP) is the first-line therapy for persistent obstructive sleep apnea despite previous adenotonsillectomy, but it is often poorly tolerated by children. When CPAP is not tolerated or preferred by the family, surgical options beyond adenotonsillectomy are discussed with the parent and child. Dynamic MRI of the airway provides a means to identify and localize the site or sites of obstruction for these children. In this review the authors address clinical indications for imaging, ideal team members to involve in an effective multidisciplinary program, basic anesthesia requirements, MRI protocol techniques and interpretation of the findings on MRI that help guide surgery. 10.1007/s00247-018-4180-2
    [Effect of oral appliance treatment on age-related changes of sleep respiratory function in patients with obstructive sleep apnea hypopnea syndrome]. Gong X,Yu M,Li W R,Gao X M Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery The severity of obstructive sleep apnea hypopnea syndrome (OSAHS) has a tendency to increase with age. The purpose of this study was to explore whether oral appliance (OA) treatment can block this age-related change. This study was a retrospective study. Fifteen patients (12 males,3 females) of OSAHS treated with OA were selected as treatment group,with an average age of (47.44±10.00) years and initial body mass index (BMI) of (26.31±3.33) kg/m(2). The follow-up length was 54 [22, 100] months. Nineteen patients (13 males,6 females) with untreated OSAHS served as controls, with an average age of (45.00±9.26) years and initial BMI of (25.53±2.58) kg/m(2),and the follow-up length was 35 [26,63] months. There were no significant differences in terms of gender,age,initial BMI, apnea hypopnea index(AHI), and follow-up length between the two groups. Polysomnography(PSG) data for the two groups were compared to observe the sleep respiratory function changes as aging by Wilcoxon test. There was no significant difference in BMI of the treatment group and the control group at the time of follow-up, with BMI of treatment group from (26.31±3.33) kg/m(2) to (25.67±3.65) kg/m(2),=-1.223,0.221; and BMI of control group from (25.53±2.58) kg/m(2) to (25.12±2.72) kg/m(2),=-1.193,0.233. There was no significant difference in the change of AHI within the treatment group, from 26.20 [11.50, 52.98]/h to 23.10 [16.00, 45.00]/h, =-0.284, 0.776; AHI in the control group was higher than that at the first visit, and the AHI increased from 15.00 [10.72, 28.90]/h to 31.10 [13.00, 41.80]/h, =-3.481, 0.001. The longest apnea duration was not statistically different in the treatment group, from 60.00 [56.40, 74.00] s to 63.00 [52.00, 77.00] s, =-0.345, 0.730; the longest apnea duration in the control group increased from 42.00 [34.00, 56.70] s to 46.00 [37.00,62.00] s,=-2.274,0.023. There was no significant difference in the lowest blood oxygen saturation of the treatment group and the control group, with the treatment group from 72.47%±12.69% to 72.73%±17.59%, =-0.597, 0.550; and the control group from 78.21%±9.30% to 76.42%±12.17%, =-0.153, 0.879. Symptoms of sleep apnea in OSAHS patients tend to increase with age,and oral appliance treatment may have the effect of slowing down this age-related worsening effect. 10.3760/cma.j.issn.1673-0860.2019.06.003
    Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer's Disease Biomarkers Changes. Liguori Claudio,Mercuri Nicola Biagio,Izzi Francesca,Romigi Andrea,Cordella Alberto,Sancesario Giuseppe,Placidi Fabio Sleep Study Objectives:Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer's Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid42, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP). Methods:We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis. Results:OSA patients showed lower CSF Aβ42 concentrations, higher CSF lactate levels, and higher t-tau/Aβ42 ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ42 levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients. Conclusions:We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ42 levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes. 10.1093/sleep/zsx011
    [Cognitive impairment in patients with COPD: a review]. Cleutjens F A H M,Janssen D J A,Gijsen C,Dijkstra J B,Ponds R W H M,Wouters E F M Tijdschrift voor gerontologie en geriatrie COPD (Chronic Obstructive Pulmonary Disease) is a respiratory disease characterized by progressive and largely irreversible airway limitation and extrapulmonary problems. The prevalence of COPD increases with age. Mental health problems, including cognitive capacity limitations, occur frequently. Patients with COPD may have problems with cognitive functioning, either globally or in single cognitive domains, such as information processing, attention and concentration, memory, executive functioning and self-regulation. Possible causes are hypoxemia, hypercapnia, exacerbations and decreased physical activity. Cognitive problems in these patients may be related to structural brain abnormalities, such as gray matter pathologic changes and the loss of white matter integrity. Because of the negative impact on health and daily life, it is important to assess cognitive functioning in patients with COPD in order to optimize patient-oriented treatment and to reduce personal discomfort, hospital admissions and mortality. 10.1007/s12439-013-0053-1
    Haemodynamic and neural responses to hypercapnia in the awake rat. Martin Chris,Jones Myles,Martindale John,Mayhew John The European journal of neuroscience The relationship between localized changes in brain activity and metabolism, and the blood oxygenation level-dependent (BOLD) signal used in functional magnetic resonance imaging studies is not fully understood. One source of complexity is that stimulus-elicited changes in the BOLD signal arise both from changes in oxygen consumption due to increases in activity and purely 'haemodynamic' changes such as increases in cerebral blood flow. It is well established that robust cortical haemodynamic changes can be elicited by increasing the concentration of inspired CO(2) (inducing hypercapnia) and it is widely believed that these haemodynamic changes occur without significant effects upon neural activity or cortical metabolism. Hypercapnia is therefore commonly used as a calibration condition in functional magnetic resonance imaging studies to enable estimation of oxidative metabolism from subsequent stimulus-evoked functional magnetic resonance imaging BOLD signal changes. However, there is little research that has investigated in detail the effects of hypercapnia upon all components of the haemodynamic response (changes in cerebral blood flow, volume and oxygenation) in addition to recording neural activity. In awake animals, we used optical and electrophysiological techniques to measure cortical haemodynamic and field potential responses to hypercapnia (60 s, 5% CO(2)). The main findings are that firstly, in the awake rat, the temporal structure of the haemodynamic response to hypercapnia differs from that reported previously in anaesthetized preparations in that the response is more rapid. Secondly, there is evidence that hypercapnia alters ongoing neural activity in awake rats by inducing periods of cortical desynchronization and this may be associated with changes in oxidative metabolism. 10.1111/j.1460-9568.2006.05135.x
    Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron. Sharma Aruna,Muresanu Dafin F,Lafuente José V,Patnaik Ranjana,Tian Z Ryan,Buzoianu Anca D,Sharma Hari S Molecular neurobiology Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB disruption and brain pathology, (ii) nanoparticles exacerbate SD-induced brain damage, and (iii) serotonin 5-HT3 receptor antagonist ondansetron is neuroprotective in SD that is further potentiated byTiO2-nanowired delivery, not reported earlier. 10.1007/s12035-015-9236-9
    Action plan interrupted: resolution of proactive interference while coordinating execution of multiple action plans during sleep deprivation. Fournier Lisa R,Hansen Devon A,Stubblefield Alexandra M,Van Dongen Hans P A Psychological research The ability to retain an action plan to execute another is necessary for most complex, goal-directed behavior. Research shows that executing an action plan to an interrupting event can be delayed when it partly overlaps (vs. does not overlap) with the retained action plan. This phenomenon is known as partial repetition costs (PRCs). PRCs reflect proactive interference, which may be resolved by inhibitory, executive control processes. We investigated whether these inhibitory processes are compromised due to one night of sleep deprivation. Participants were randomized to a sleep-deprived group or a well-rested control group. All participants performed an action planning task at baseline after a full night of sleep, and again either after a night of sleep deprivation (sleep-deprived group) or a full night of sleep (control group). In this task, two visual events occurred in a sequence. Participants retained an action plan to the first event in working memory while executing a speeded action to the second (interrupting) event; afterwards, they executed the action to the first event. The two action plans either partly overlapped (required the same hand) or did not (required different hands). Results showed slower responses to the interrupting event during sleep deprivation compared to baseline and the control group. However, the magnitude of the PRCs was no different during sleep deprivation compared to baseline and the control group. Thus, one night of sleep deprivation slowed global responses to the interruption, but inhibitory processes involved in reducing proactive interference while responding to an interrupting event were not compromised. These findings are consistent with other studies that show sleep deprivation degrades global task performance, but does not necessarily degrade performance on isolated, executive control components of cognition. The possibility that our findings involve local as opposed to central inhibition is also discussed. 10.1007/s00426-018-1054-z
    Sleep architecture changes in the APP23 mouse model manifest at onset of cognitive deficits. Van Erum Jan,Van Dam Debby,Sheorajpanday Rishi,De Deyn Peter Paul Behavioural brain research Alzheimer's disease (AD), which accounts for most of the dementia cases, is, aside from cognitive deterioration, often characterized by the presence of non-cognitive symptoms such as activity and sleep disturbances. AD patients typically experience increased sleep fragmentation, excessive daytime sleepiness and night-time insomnia. Here, we sought to investigate the link between sleep architecture, cognition and amyloid pathology in the APP23 amyloidosis mouse model for AD. By means of polysomnographic recordings the sleep-wake cycle of freely-moving APP23 and wild-type (WT) littermates of 3, 6 and 12 months of age was examined. In addition, ambulatory cage activity was assessed by interruption of infrared beams surrounding the home cage. To assess visuo-spatial learning and memory a hidden-platform Morris-type Water Maze (MWM) experiment was performed. We found that sleep architecture is only slightly altered at early stages of pathology, but significantly deteriorates from 12 months of age, when amyloid plaques become diffusely present. APP23 mice of 12 months old had quantitative reductions of NREM and REM sleep and were more awake during the dark phase compared to WT littermates. These findings were confirmed by increased ambulatory cage activity during that phase of the light-dark cycle. No quantitative differences in sleep parameters were observed during the light phase. However, during this light phase, the sleep pattern of APP23 mice was more fragmented from 6 months of age, the point at which also cognitive abilities started to be affected in the MWM. Sleep time also positively correlated with MWM performance. We also found that spectral components in the EEG started to alter at the age of 6 months. To conclude, our results indicate that sleep architectural changes arise around the time the first amyloid plaques start to form and cognitive deterioration becomes apparent. These changes start subtle, but gradually worsen with age, adequately mimicking the clinical condition. 10.1016/j.bbr.2019.112089
    The protective effect of 20(S)-protopanaxadiol (PPD) against chronic sleep deprivation (CSD)-induced memory impairments in mice. Lu Cong,Lv Jingwei,Dong Liming,Jiang Ning,Wang Yan,Fan Bei,Wang Fengzhong,Liu Xinmin Brain research bulletin Sleep deprivation (SD) is associated with oxidative stress that causes learning and memory impairment. 20(S)-Protopanaxadiol (PPD), one of the protopanaxadiol-type saponins, has antioxidant and neuroprotective effect. This study was designed to research the protective effect of PPD against cognitive deficits induced by chronic sleep deprivation (CSD) in mice. The CSD model was induced by subjecting the mice to our self-made Sleep Interruption Apparatus (SIA) continuously for 14 days. The memory enhancing effects of PPD were evaluated by behavioral tests and the related mechanism was further explored by observing the oxidative stress changes in the cortex and hippocampus of mice. The results revealed that PPD (20 and 40 μmol/kg, i.p.) administration significantly improved the cognitive performance of CSD model mice in object location recognition experiment, novel object recognition task and Morris water maze test. Furthermore, PPD effectively restored the levels/activities of antioxidant defense biomarkers in the cortex and hippocampus, including the superoxide dismutase (SOD) enzyme activity, catalase (CAT) enzyme activity, glutathione (GSH), and lipid peroxidation (LPO). In conclusion, PPD could attenuate cognitive deficits induced by CSD, and the neuroprotective effect of PPD might be mediated by alleviation of oxidative stress. It was assumed that PPD has the potential to be a neuroprotective substance for cognition dysfunction. 10.1016/j.brainresbull.2017.12.012
    Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method. Feng Li,Wu Hong-wei,Song Guang-qing,Lu Cong,Li Ying-hui,Qu Li-na,Chen Shan-guang,Liu Xin-min,Chang Qi Behavioural brain research Good sleep is necessary for optimal health, especially for mental health. Insomnia, sleep deprivation will make your ability to learn and memory impaired. Nevertheless, the underlying pathophysiological mechanism of sleep disorders-induced cognitive decline is still largely unknown. In this study, the sleep deprivation of animal model was induced by chronical sleep interruption (CSI), the behavioral tests, biochemical index determinations, and a liquid chromatography-mass spectrometry (LC-MS) based serum metabolic profiling analysis were performed to explore the effects of CSI on cognitive function and the underlying mechanisms. After 14-days CSI, the cognitive function of the mice was evaluated by new objects preference (NOP) task and temporal order judgment (TOJ) task. Serum corticosterone (CORT), and brain Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT) levels were determined by ELISA kits. Data were analyzed by Principal Component Analysis (PCA), Partial Least Squares project to latent structures-Discriminant Analysis (PLS-DA), and Student's t-test. We found that the cognitive function of the mice was significantly affected by CSI. Besides, levels of CORT and MDA were higher, and SOD and CAT were lower in CSI mice than those of control. Obvious body weight loss of CSI mice was also observed. Thirteen potential serum biomarkers including choline, valine, uric acid, allantoic acid, carnitines, and retinoids were identified. Affected metabolic pathways involve metabolism of purine, retinoid, lipids, and amino acid. These results showed that CSI can damage the cognitive performance notably. The cognitive decline may ascribe to excessive oxidative stress and a series of disturbed metabolic pathways. 10.1016/j.bbr.2015.12.039
    Obstructive sleep apnea and longitudinal Alzheimer's disease biomarker changes. Bubu Omonigho M,Pirraglia Elizabeth,Andrade Andreia G,Sharma Ram A,Gimenez-Badia Sandra,Umasabor-Bubu Ogie Q,Hogan Megan M,Shim Amanda M,Mukhtar Fahad,Sharma Nidhi,Mbah Alfred K,Seixas Azizi A,Kam Korey,Zizi Ferdinand,Borenstein Amy R,Mortimer James A,Kip Kevin E,Morgan David,Rosenzweig Ivana,Ayappa Indu,Rapoport David M,Jean-Louis Girardin,Varga Andrew W,Osorio Ricardo S, Sleep STUDY OBJECTIVES:To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (Aβ42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer's disease (AD) elderly. METHODS:Longitudinal study with mean follow-up time of 2.52 ± 0.51 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF Aβ42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA. RESULTS:In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B = .06, 95% CI = .02, .11 and B = .08, 95% CI = .05, .12, respectively) and decrease in CSF Aβ42 levels (B = -2.71, 95% CI = -3.11, -2.35 and B = -2.62, 95% CI = -3.23, -2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA- participants. No significant variations in the biomarker changes over time were seen in the AD group. CONCLUSIONS:In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD. 10.1093/sleep/zsz048
    Age differences in the association of obstructive sleep apnea risk with cognition and quality of life. Addison-Brown Kristin J,Letter Abraham J,Yaggi Klar,McClure Leslie A,Unverzagt Frederick W,Howard Virginia J,Lichtman Judith H,Wadley Virginia G Journal of sleep research Using a sample of 2925 stroke-free participants drawn from a national population-based study, we examined cross-sectional associations of obstructive sleep apnea (OSA) risk with cognition and quality of life and whether these vary with age, while controlling for demographics and comorbidities. Included participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were aged 47-93 years. OSA risk was categorized as high or low based on responses to the Berlin Sleep Questionnaire. Cognitive function was assessed with standardized fluency and recall measures. Depressive symptoms were assessed with the four-item Center for Epidemiologic Studies Depression Scale. Health-related quality of life (HRQoL) was assessed with the Medical Outcomes Study Short Form-12 (SF-12). Multivariate analyses of covariance (mancova) statistics were applied separately to the cognitive and quality of life dependent variables while accounting for potential confounders (demographics, comorbidities). In fully adjusted models, those at high risk for OSA had significantly lower cognitive scores (Wilks' lambda = 0.996, F3,2786  = 3.31, P < 0.05) and lower quality of life [depressive symptoms and HRQoL] (Wilks' lambda = 0.989, F3,2786  = 10.02, P < 0.0001). However, some of the associations were age-dependent. Differences in cognition and quality of life between those at high and low obstructive sleep apnea risk were most pronounced during middle age, with attenuated effects after age 70 years. 10.1111/jsr.12086
    Factors associated with the severity of obstructive sleep apnea in older adults. Hongyo Kazuhiro,Ito Norihisa,Yamamoto Koichi,Yasunobe Yukiko,Takeda Masao,Oguro Ryosuke,Takami Yoichi,Takeya Yasushi,Sugimoto Ken,Rakugi Hiromi Geriatrics & gerontology international AIM:Epidemiological studies have shown that severe obstructive sleep apnea (OSA) is associated with higher mortality when compared with mild to moderate OSA. Because aging is a well-known risk factor for OSA, we aimed to elucidate the underlying factors associated with the severity of OSA in elderly patients. METHODS:Patients who underwent polysomnography were divided into the non-elderly group (aged <65 years; n = 44) and the elderly group (aged ≥65 years; n = 46). The severity of OSA was determined by the apnea hypopnea index (AHI), and each group was subdivided into two groups: mild to moderate OSA (5 < AHI < 30) and severe OSA (AHI ≥30) . In the elderly group, geriatric assessments to evaluate physical and neuropsychiatric function were carried out. RESULTS:All patients had OSA as diagnosed by an AHI >5. Whereas body mass index was positively correlated with AHI in both groups, age was correlated with AHI only in the elderly group. Body mass index and age were higher in severe OSA than mild to moderate OSA in the elderly group. Unexpectedly, no significant difference was observed in physical strength, cognitive function, apathy scale, depression scale or activities of daily living between mild to moderate OSA and severe OSA in the elderly group. Binary logistic regression analysis showed that male sex, body mass index and aging were independent risk factors of severe OSA in the elderly group. CONCLUSIONS:Our findings suggest that aging increases the severity of OSA in elderly patients, even if they are physically active and neuropsychiatrically unimpaired. Geriatr Gerontol Int 2017; 17: 614-621. 10.1111/ggi.12768
    Update on Research and Practices in Major Sleep Disorders: Part I. Obstructive Sleep Apnea Syndrome. Chaiard Jindarat,Weaver Terri E Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing PURPOSE:The purpose of this first of two review articles providing an update on sleep disorders was to examine the pathophysiology, epidemiology, and treatment of obstructive sleep apnea (OSA). OSA is a common sleep disorder whose prevalence is similar to asthma. As with other sleep disorders, OSA has a broad impact on individuals, affecting their daily behaviors, cognitive abilities, and performance, and putting them at increased risk for accidents, mood disorders, cancer, cardiovascular disease, and hypertension. Thus, early recognition and management, much of which can be implemented by nurses, can reduce health and accident risks and improve daily functioning. METHODS:This narrative review utilized medical databases such as PubMed to identify relevant English language original and systematic review articles predominantly from peer-reviewed journals from 2012 to 2018. However, as background, findings from classic articles prior to 2012 were also included. CLINICAL RELEVANCE:OSA is a common condition with considerable impact on daily functioning and potential for accidents and serious comorbidities such as hypertension, cardiovascular disease, diabetes, and depressed mood. The impairments and comorbidities associated with OSA can be reduced through early detection, encouraging treatment, providing education about sleep and OSA, and, importantly, promoting adherence to the predominant therapy, positive airway pressure. 10.1111/jnu.12489
    Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study. Sharma Ram A,Varga Andrew W,Bubu Omonigho M,Pirraglia Elizabeth,Kam Korey,Parekh Ankit,Wohlleber Margaret,Miller Margo D,Andrade Andreia,Lewis Clifton,Tweardy Samuel,Buj Maja,Yau Po L,Sadda Reem,Mosconi Lisa,Li Yi,Butler Tracy,Glodzik Lidia,Fieremans Els,Babb James S,Blennow Kaj,Zetterberg Henrik,Lu Shou E,Badia Sandra G,Romero Sergio,Rosenzweig Ivana,Gosselin Nadia,Jean-Louis Girardin,Rapoport David M,de Leon Mony J,Ayappa Indu,Osorio Ricardo S American journal of respiratory and critical care medicine RATIONALE:Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. OBJECTIVES:To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. METHODS:Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. MEASUREMENTS AND MAIN RESULTS:We found that severity of OSA indices (AHIall [F = 4.26; P < 0.05] and AHI4% [F = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in AD-mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F = 2.96, P = 0.09; and F = 2.32, not significant, respectively). CONCLUSIONS:In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly. 10.1164/rccm.201704-0704OC
    Obstructive sleep apnea, cognition and Alzheimer's disease: A systematic review integrating three decades of multidisciplinary research. Bubu Omonigho M,Andrade Andreia G,Umasabor-Bubu Ogie Q,Hogan Megan M,Turner Arlener D,de Leon Mony J,Ogedegbe Gbenga,Ayappa Indu,Jean-Louis G Girardin,Jackson Melinda L,Varga Andrew W,Osorio Ricardo S Sleep medicine reviews Increasing evidence links cognitive-decline and Alzheimer's disease (AD) to various sleep disorders, including obstructive sleep apnea (OSA). With increasing age, there are substantial differences in OSA's prevalence, associated comorbidities and phenotypic presentation. An important question for sleep and AD researchers is whether OSA's heterogeneity results in varying cognitive-outcomes in older-adults compared to middle-aged adults. In this review, we systematically integrated research examining OSA and cognition, mild cognitive-impairment (MCI) and AD/AD biomarkers; including the effects of continuous positive airway pressure (CPAP) treatment, particularly focusing on characterizing the heterogeneity of OSA and its cognitive-outcomes. Broadly, in middle-aged adults, OSA is often associated with mild impairment in attention, memory and executive function. In older-adults, OSA is not associated with any particular pattern of cognitive-impairment at cross-section; however, OSA is associated with the development of MCI or AD with symptomatic patients who have a higher likelihood of associated disturbed sleep/cognitive-impairment driving these findings. CPAP treatment may be effective in improving cognition in OSA patients with AD. Recent trends demonstrate links between OSA and AD-biomarkers of neurodegeneration across all age-groups. These distinct patterns provide the foundation for envisioning better characterization of OSA and the need for more sensitive/novel sleep-dependent cognitive assessments to assess OSA-related cognitive-impairment. 10.1016/j.smrv.2019.101250
    The Relationship between Obstructive Sleep Apnea and Alzheimer's Disease. Andrade Andreia G,Bubu Omonigho M,Varga Andrew W,Osorio Ricardo S Journal of Alzheimer's disease : JAD Obstructive sleep apnea (OSA) and Alzheimer's disease (AD) are highly prevalent conditions with growing impact on our aging society. While the causes of OSA are now better characterized, the mechanisms underlying AD are still largely unknown, challenging the development of effective treatments. Cognitive impairment, especially affecting attention and executive functions, is a recognized clinical consequence of OSA. A deeper contribution of OSA to AD pathogenesis is now gaining support from several lines of research. OSA is intrinsically associated with disruptions of sleep architecture, intermittent hypoxia and oxidative stress, intrathoracic and hemodynamic changes as well as cardiovascular comorbidities. All of these could increase the risk for AD, rendering OSA as a potential modifiable target for AD prevention. Evidence supporting the relevance of each of these mechanisms for AD risk, as well as a possible effect of AD in OSA expression, will be explored in this review. 10.3233/JAD-179936
    Pediatric obstructive sleep apnea. Schwengel Deborah A,Dalesio Nicholas M,Stierer Tracey L Anesthesiology clinics Obstructive sleep apnea syndrome (OSAS) is a disorder of airway obstruction with multisystem implications and associated complications. OSAS affects children from infancy to adulthood and is responsible for behavioral, cognitive, and growth impairment as well as cardiovascular and perioperative respiratory morbidity and mortality. OSAS is associated commonly with comorbid conditions, including obesity and asthma. Adenotonsillectomy is the most commonly used treatment option for OSAS in childhood, but efforts are underway to identify medical treatment options. 10.1016/j.anclin.2013.10.012
    Risk of Alzheimer's Disease in Obstructive Sleep Apnea Syndrome: Amyloid-β and Tau Imaging. Elias Alby,Cummins Tia,Tyrrell Regan,Lamb Fiona,Dore Vincent,Williams Robert,Rosenfeld J V,Hopwood Malcolm,Villemagne Victor L,Rowe Christopher C Journal of Alzheimer's disease : JAD BACKGROUND:An association between obstructive sleep apnea (OSA) and Alzheimer's disease has been suggested but little is known about amyloid-β and tau deposition in this syndrome. OBJECTIVE:To determine amyloid and tau burden and cognitive function in OSA in comparison with those without a diagnosis of OSA. METHODS:The status of OSA was determined by asking participants about history of polysomnographic diagnosis of OSA and the use of Continuous Positive Airway Pressure (CPAP). A comprehensive neuropsychological battery measured cognitive function. Positron emission tomography (PET) was used to measure standardized uptake value ratio (SUVR) of 18F-florbetaben and 18F-AV1451, to quantify amyloid and tau burden. RESULTS:119 male Vietnam veterans completed assessment. Impairment in visual attention and processing speed and increased body mass index (BMI) were seen in subjects with OSA compared with those without a diagnosis OSA. The cortical uptake of 18F-florbetaben was higher in the OSA group than in the control group (SUVR: 1.35±0.21 versus 1.27±0.16, p = 0.04). There were more apolipoprotein E ɛ4 allele (APOE ɛ4) carriers in the OSA group than in the control group. In multilinear regression analysis, the significance of OSA in predicting 18F-florbetaben uptake remained independent of age and vascular risk factors but not when BMI or APOE ɛ4 was adjusted. The reported use of CPAP (n = 14) had no effect on cognitive or amyloid PET findings. There was no significant difference in 18F-AV1451 uptake between the two groups. CONCLUSIONS:Obstructive sleep apnea is associated with Alzheimer's disease pathology, but this relationship is moderated by APOE ɛ4 and BMI. 10.3233/JAD-180640
    Association between mild or moderate obstructive sleep apnea-hypopnea syndrome and cognitive dysfunction in children. Zhao Jing,Han Shujing,Zhang Jishui,Wang Guixiang,Wang Hua,Xu Zhifei,Tai Jun,Peng Xiaoxia,Guo Yongli,Liu Haihong,Tian Jinghong,Jin Xin,Zheng Li,Zhang Jie,Ni Xin Sleep medicine BACKGROUND:Childhood obstructive sleep apnea-hypopnea syndrome (OSAHS), the most common sleep-related breathing disorder, may lead to cognitive impairment. This study aims to investigate the association between mild or moderate childhood OSAHS and cognitive dysfunction. METHODS:A total of 59 children (4-12 years of age) diagnosed with mild or moderate OSAHS by polysomnography and 60 age-  and sex-matched healthy children were included in the study. The China-Wechsler Younger Children Scale of Intelligence and China-Wechsler Intelligence Scale for Children were used to evaluate the cognition of the participating children aged <6 years and ≥6 years, respectively. RESULTS:In the <6-years-old subgroup, children with OSAHS had significantly lower scores of full-scale IQ (FIQ), verbal IQ (VIQ), comprehension test, and visual analysis than the healthy children (all p < 0.05). In the ≥6-years-old subgroup, VIQ and classification test scores were significantly lower in children with OSAHS than in the healthy controls (all p < 0.05). FIQ, VIQ, and performance IQ (PIQ) scores did not correlate with AHI, OAHI, and the lowest nocturnal SO. Notably, in the <6-years-old subgroup of OSAHS, the accumulated time of SO<90% (p = 0.046) and the percentage of the accumulated time of SO<90% in the total sleep time (p = 0.034) correlated with PIQ negatively and significantly. CONCLUSIONS:Mild to moderate childhood OSAHS may adversely affect cognitive function, particularly in young children (<6 years of age). This study may increase the awareness of childhood OSAHS-associated cognitive dysfunction and advocate early interventions in childhood OSAHS. 10.1016/j.sleep.2018.04.009
    The prevalence of obstructive sleep apnea in mild cognitive impairment: a systematic review. Mubashir Talha,Abrahamyan Lusine,Niazi Ayan,Piyasena Deween,Arif Abdul A,Wong Jean,Osorio Ricardo S,Ryan Clodagh M,Chung Frances BMC neurology BACKGROUND:Previous studies have shown that obstructive sleep apnea (OSA) is associated with a higher risk of cognitive impairment or dementia in the elderly, leading to deleterious health effects and decreasing quality of life. This systematic review aims to determine the prevalence of OSA in patients with mild cognitive impairment (MCI) and examine whether an association between OSA and MCI exists. METHODS:We searched Medline, PubMed, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsychINFO, Scopus, the Web of Science, ClinicalTrials.gov and the International Clinical Trials Registry Platform for published and unpublished studies. We included studies in adults with a diagnosis of MCI that reported on the prevalence of OSA. Two independent reviewers performed the abstract and full-text screening, data extraction and the study quality critical appraisal. RESULTS:Five studies were included in the systematic review. Overall, OSA prevalence rates in patients with MCI varied between 11 and 71% and were influenced by OSA diagnostic methods and patient recruitment locations (community or clinic based). Among studies using the following OSA diagnostic measures- self-report, Home Sleep Apnea Testing, Berlin Questionnaire and polysomnography- the OSA prevalence rates in MCI were 11, 27, 59 and 71%, respectively. In a community-based sample, the prevalence of OSA in patients with and without MCI was 27 and 26%, respectively. CONCLUSIONS:Based on limited evidence, the prevalence of OSA in patients with MCI is 27% and varies based upon OSA diagnostic methods and patient recruitment locations. Our findings provide an important framework for future studies to prospectively investigate the association between OSA and MCI among larger community-based cohorts and implement a standardized approach to diagnose OSA in memory clinics. PROSPERO REGISTRATION:CRD42018096577. 10.1186/s12883-019-1422-3
    Obstructive sleep apnea exaggerates cognitive dysfunction in stroke patients. Zhang Yan,Wang Wanhua,Cai Sijie,Sheng Qi,Pan Shenggui,Shen Fang,Tang Qing,Liu Yang Sleep medicine BACKGROUND:Obstructive sleep apnea (OSA) is very common in stroke survivors. It potentially worsens the cognitive dysfunction and inhibits their functional recovery. However, whether OSA independently damages the cognitive function in stroke patients is unclear. A simple method for evaluating OSA-induced cognitive impairment is also missing. METHODS:Forty-four stroke patients six weeks after onset and 24 non-stroke patients with snoring were recruited for the polysomnographic study of OSA and sleep architecture. Their cognitive status was evaluated with a validated Chinese version of Cambridge Prospective Memory Test. The relationship between memory deficits and respiratory, sleeping, and dementia-related clinical variables were analyzed with correlation and multiple linear regression tests. RESULTS:OSA significantly and independently damaged time- and event-based prospective memory in stroke patients, although it had less power than the stroke itself. The impairment of prospective memory was correlated with increased apnea-hypopnea index, decreased minimal and mean levels of peripheral oxygen saturation, and disrupted sleeping continuity (reduced sleep efficiency and increased microarousal index). The further regression analysis identified minimal levels of peripheral oxygen saturation and sleep efficiency to be the two most important predictors for the decreased time-based prospective memory in stroke patients. CONCLUSIONS:OSA independently contributes to the cognitive dysfunction in stroke patients, potentially through OSA-caused hypoxemia and sleeping discontinuity. The prospective memory test is a simple but sensitive method to detect OSA-induced cognitive impairment in stroke patients. Proper therapies of OSA might improve the cognitive function and increase the life quality of stroke patients. 10.1016/j.sleep.2016.11.028
    Association of Mild Obstructive Sleep Apnea With Cognitive Performance, Excessive Daytime Sleepiness, and Quality of Life in the General Population: The Korean Genome and Epidemiology Study (KoGES). Kim Hyun,Thomas Robert J,Yun Chang-Ho,Au Rhoda,Lee Seung Ku,Lee Sunghee,Shin Chol Sleep Study Objectives:Research points to impaired cognitive performance in sleep clinic patients with obstructive sleep apnea (OSA). However, inconsistent findings from various epidemiologic studies make this relationship less generalizable. The current study investigated the association between OSA and functional outcome measures, such as cognition, daytime sleepiness, and quality of life, in a Korean general population sample. Methods:A total of 1492 participants from the Korean Genome and Epidemiology Study (KoGES) were included in the analyses. The presence of OSA measured by overnight polysomnography (PSG) was defined by apnea-hypopnea index (AHI) >5. Cognitive performance was determined with scores from a comprehensive neuropsychological battery. Excessive daytime sleepiness and quality of life were additionally measured through subjective reports. Results:After adjusting for various demographic and medical characteristics, OSA was independently associated with lower performance in the Digit Symbol Test (52.73 ± 17.08 vs. 58.72 ± 18.03, OSA vs. not, p = .02). Hypoxia measures were not related to cognitive performance. OSA was associated with higher odds of displaying excessive daytime sleepiness (odds ratio = 1.72, 95% CI: 1.05-2.80), but there was no significant relationship between OSA and quality of life. Conclusions:Cognition was unexpectedly unaffected overall. However, OSA was associated with impairment in a multidomain test that taps skills generally associated with frontal lobe function. The results suggest that research on protective and adaptive brain mechanisms to OSA stress can provide unique insights into the brain-sleep interface. As the study runs longitudinally, it will enable future studies on the impact of OSA on cognitive decline. 10.1093/sleep/zsx012
    Prevalence of obstructive sleep apnea in Alzheimer's disease patients. Gaeta Anna Michela,Benítez Ivan D,Jorge Carmen,Torres Gerard,Dakterzada Faride,Minguez Olga,Huerto Raquel,Pujol Montse,Carnes Anna,Dalmases Mireia,Gibert Aurora,Farré Ramón,de la Torres Manuel Sanchez,Barbé Ferran,Piñol-Ripoll Gerard Journal of neurology OBJECTIVE:To assess the prevalence of obstructive sleep apnea (OSA) in patients with mild-moderate Alzheimer's Disease (AD) and to evaluate cognitive characteristics according to the severity of OSA. METHODS:Patients with mild-moderate AD, recruited prospectively from a cognitive impairment unit, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index > 5/h. AD severity was assessed using the Mini-Mental State Examination and extensive neuropsychological battery. Epworth Sleepiness Scale and APOE status were analyzed. RESULTS:The cohort included 128 patients with a median [IQR] age of 75.0 [72.0;79.2] years and 57.8% were women. OSA was diagnosed in 116 subjects (90.6%). The distribution of mild, moderate and severe severity of OSA was 29 (22.7%), 37 (28.9%) and 50 (39.1%), respectively. Regarding sleep symptoms, the cohort showed normal values of daytime sleepiness (median EES score 5 [3, 8]), while nycturia (89.1%) and snoring (71.1%) were the most common symptoms. Participants with severe OSA included a higher proportion of older men, were associated with snoring and sedentariness. No significant differences in cognitive assessment were found between patients with and without severe OSA in any of the domains. The prevalence of APOE ε4 was not significantly different between patients with and without severe OSA. CONCLUSION:There was a high prevalence of OSA in patients with mild-moderate AD. OSA was not associated with sleepiness or worse cognitive function. APOE ε4 was not related to the presence or severity of OSA. Further longitudinal studies will be required to evaluate whether OSA impairs cognitive evolution in AD patients. 10.1007/s00415-019-09668-4
    Cognitive impairment in obstructive sleep apnea. Gagnon K,Baril A-A,Gagnon J-F,Fortin M,Décary A,Lafond C,Desautels A,Montplaisir J,Gosselin N Pathologie-biologie Obstructive sleep apnea (OSA) is characterised by repetitive cessation or reduction of airflow due to upper airway obstructions. These respiratory events lead to chronic sleep fragmentation and intermittent hypoxemia. Several studies have shown that OSA is associated with daytime sleepiness and cognitive dysfunctions, characterized by impairments of attention, episodic memory, working memory, and executive functions. This paper reviews the cognitive profile of adults with OSA and discusses the relative role of altered sleep and hypoxemia in the aetiology of these cognitive deficits. Markers of cognitive dysfunctions such as those measured with waking electroencephalography and neuroimaging are also presented. The effects of continuous positive airway pressure (CPAP) on cognitive functioning and the possibility of permanent brain damage associated with OSA are also discussed. Finally, this paper reviews the evidence suggesting that OSA is a risk factor for developing mild cognitive impairment and dementia in the aging population and stresses the importance of its early diagnosis and treatment. 10.1016/j.patbio.2014.05.015
    Changes in Neurocognitive Architecture in Patients with Obstructive Sleep Apnea Treated with Continuous Positive Airway Pressure. Rosenzweig Ivana,Glasser Martin,Crum William R,Kempton Matthew J,Milosevic Milan,McMillan Alison,Leschziner Guy D,Kumari Veena,Goadsby Peter,Simonds Anita K,Williams Steve C R,Morrell Mary J EBioMedicine BACKGROUND:Obstructive sleep apnea (OSA) is a chronic, multisystem disorder that has a bidirectional relationship with several major neurological disorders, including Alzheimer's dementia. Treatment with Continuous Positive Airway Pressure (CPAP) offers some protection from the effects of OSA, although it is still unclear which populations should be targeted, for how long, and what the effects of treatment are on different organ systems. We investigated whether cognitive improvements can be achieved as early as one month into CPAP treatment in patients with OSA. METHODS:55 patients (mean (SD) age: 47.6 (11.1) years) with newly diagnosed moderate-severe OSA (Oxygen Desaturation Index: 36.6 (25.2) events/hour; Epworth sleepiness score (ESS): 12.8 (4.9)) and 35 matched healthy volunteers were studied. All participants underwent neurocognitive testing, neuroimaging and polysomnography. Patients were randomized into parallel groups: CPAP with best supportive care (BSC), or BSC alone for one month, after which they were re-tested. FINDINGS:One month of CPAP with BSC resulted in a hypertrophic trend in the right thalamus [mean difference (%): 4.04, 95% CI: 1.47 to 6.61], which was absent in the BSC group [-2.29, 95% CI: -4.34 to -0.24]. Significant improvement was also recorded in ESS, in the CPAP plus BSC group, following treatment [mean difference (%): -27.97, 95% CI: -36.75 to -19.19 vs 2.46, 95% CI: -5.23 to 10.15; P=0.012], correlated to neuroplastic changes in brainstem (r=-0.37; P=0.05), and improvements in delayed logical memory scores [57.20, 95% CI: 42.94 to 71.46 vs 23.41, 95% CI: 17.17 to 29.65; P=0.037]. INTERPRETATION:One month of CPAP treatment can lead to adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness, and improved verbal episodic memory in patients with OSA. We propose that partial neural recovery occurs during short periods of treatment with CPAP. 10.1016/j.ebiom.2016.03.020
    [Obstructive sleep apnea syndrome and cognition: A review]. Daurat Agnès,Sarhane Majdouline,Tiberge Michel Neurophysiologie clinique = Clinical neurophysiology Obstructive sleep apnea syndrome (OSAS) is a sleep-related breathing disorder characterized by repetitive episodes of airflow cessation, resulting in brief arousals and intermittent hypoxemia. OSAS is associated with a number of adverse health consequences, and cognitive difficulties. The overall pattern of cognitive impairment in OSAS is complex, and research in this field is mixed. On balance, OSAS have negative effects on cognition, most likely in the domain of attention/vigilance, verbal and visual delayed long-term memory, and executive functions. A still unanswered question is whether these deficits are primarily a consequence of sleep fragmentation and/or hypoxemia, or whether they coexist independently from OSAS. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment of OSAS. No consistent effect of CPAP use on cognitive performance was evident. This may be due, in part, to variability in study design and sampling methodology across studies. Structural changes have been reported in different brain regions, particularly in hippocampus and frontal cortex. Recent evidence suggests that the OSAS-related structural changes may improve with CPAP treatment. However, one of the challenges is to interpret the findings in light of comorbid conditions that also cause neural lesions. Animal models will be specifically useful to disentangle the different potential contributors to cognitive impairment in OSAS. The purpose of this article is to provide a review of the literature on cognition and neuroimaging in OSAS patients before and after CPAP treatment. We also discuss the mechanisms that have been proposed to explain cognitive deficits in OSAS patients. 10.1016/j.neucli.2016.04.002
    Pharmacotherapy for residual excessive sleepiness and cognition in CPAP-treated patients with obstructive sleep apnea syndrome: A systematic review and meta-analysis. Avellar Ariane B C C,Carvalho Luciane B C,Prado Gilmar F,Prado Lucila B F Sleep medicine reviews Pharmacotherapy has been used as an adjunct to CPAP for treatment of residual excessive sleepiness in patients with a diagnosis of obstructive sleep apnea syndrome (OSAS). However, no studies with a high level of evidence have been conducted to support this practice and confirm its effectiveness. We conducted a meta-analysis to summarize and quantify the effects of pharmacological treatment in adults with OSAS who experience residual excessive sleepiness despite adequate CPAP use. We reviewed clinical trials that compared medications to placebo and evaluated the outcomes residual excessive sleepiness, cognition, and quality of life, as well as treatment effectiveness and safety. The MEDLINE, EMBASE, LILACS, Cochrane Central Register of Controlled Trials - CENTRAL, and PsycINFO electronic databases were searched using highly sensitive search strategies. Trials were only included if measures were taken to ensure effective CPAP treatment. Eight randomized clinical trials were included. Pharmacotherapy with modafinil and armodafinil led to improvement of excessive daytime sleepiness, attention/alertness, and clinical condition as measured with the CGI-C. No improvements in quality of life or other cognitive domains (including memory, executive function, and language) could be confirmed. Pharmacotherapy did not cause any severe adverse effects, but was associated with significant dropout rates as compared with placebo. In conclusion, although our results demonstrate the effectiveness of pharmacological treatment as an adjunct to CPAP, further investigation is necessary to improve confidence in its effects. Many findings on the impact of pharmacotherapy on cognition and quality of life were evaluated through analysis of single studies, with heterogeneity in tests and absence of standardization, which reduced certainty as to whether actual improvement occurred in these outcomes. 10.1016/j.smrv.2015.10.005
    Obstructive sleep apnea: neurocognitive and behavioral functions before and after treatment. Turner Katherine,Zambrelli Elena,Lavolpe S,Baldi C,Furia F,Canevini Maria Paola Functional neurology Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized by repetitive episodes of upper airway obstruction. The aim of this study was to evaluate whether continuous positive airway pressure (CPAP) treatment is linked to improvements in cognitive abilities and emotional functions of patients with OSAS. Following the exclusion of four subjects for non-adherence to CPAP treatment, the final study sample was composed of 16 patients with moderate-to-severe OSAS, who were assessed both prior to and after 3 months of CPAP treatment, using a neuropsychological battery and questionnaires to assess mood and anxiety disorders, irritability, quality of life, quality of sleep and daytime sleepiness. We observed significant improvements in Digit Span Backward, Short Story and Corsi Span performances after 3 months of CPAP treatment. Questionnaires showed a significant reduction in daytime sleepiness and improvements in the subjective perception of sleep quality and sleep efficiency, and reduced daytime dysfunction. CPAP treatment has significant effects on different cognitive domains in patients with OSAS, especially working memory, long-term verbal memory, and short-term visuospatial memory.
    [Associations between objective sleepiness and cognition function before and after CPAP in obstructive sleep apnea patients]. Lei F,Li T M,Tan L,Ren R,Tang X D,Yang L H Zhonghua yi xue za zhi To examine the association between objective sleepiness and neurocognitive function before and after continuous positive airway pressure (CPAP) in obstructive sleep apnea (OSA) patients. A total of 53 patients with overnight polysomnography (PSG) determined moderate-to-severe OSA (apnea hypopnea index (AHI) ≥15 events/h) and with overnight CPAP therapy from West China Hospital, Sichuan University within the period from Feb 2018 to Dec 2018 were enrolled in the study. At the baseline, all patients underwent overnight PSG study, multiple sleep latency test (MSLT), psychomotor vigilance test (PVT), and Epworth sleepiness score (ESS). After CPAP therapy, all patients underwent MSLT and PVT. Paired nonparametric test or test were used to compare the differences between daytime sleepiness and PVT performance before and after CPAP. Compared with baseline data, AHI [68.8(42.2, 80.0) vs 7.4(3.1, 11.1) events/h, 0.05] decreased, the percentages of non-rapid eye movement stage 3 sleep time [0(0, 0.5%) vs 4.4%(1.9%, 11.3%), 0.05] and the percentages of rapid eye movement sleep time [18.6%(13.2%, 22.7%) vs 25.4%(23.85, 30.3%), 0.05] increased after CPAP therapy. The reaction time (RT) [353.0(317.5, 429.5) vs 333.6(309.7, 381.4) ms, 0.05], the slowest 10% RT [602.9(473.2, 841.3) vs 505.5(431.6, 618.8) ms, 0.05] and the fastest 10% RT [260.8(236.6, 300.6) vs 251.4(233.6, 283.2) ms, 0.05] shortened, and the lapse [6.0(2.5, 16.5) vs 3.0(1.0, 8.5) events, 0.05] decreased. The mean sleep latency (MSL) [5.8 (3.4, 8.3) vs 7.5(4.7, 12.4) min, 0.05] increased. The changes in PVT parameters [ΔRT (0.20, 0.05), Δslowest 10% RT (0.15, 0.05), Δfastest 10% RT (0.24, 0.05), and Δlapse (0.15, 0.05)] were not correlated with the change in MSL. The significant association between the slowest 10% RT and ESS was found in baseline data. The change in MSL is not associated with the change in PVT performance before and after CPAP therapy. MSLT and PVT may be different in nature. 10.3760/cma.j.issn.0376-2491.2019.28.006
    Executive dysfunction in OSA before and after treatment: a meta-analysis. Olaithe Michelle,Bucks Romola S Sleep STUDY OBJECTIVES:Obstructive sleep apnea (OSA) is a frequent and often underdiagnosed condition that is associated with upper airway collapse, oxygen desaturation, and sleep fragmentation leading to cognitive dysfunction. There is meta-analytic evidence that subdomains of attention and memory are affected by OSA. However, a thorough investigation of the impact of OSA on different subdomains of executive function is yet to be conducted. This report investigates the impact of OSA and its treatment, in adult patients, on 5 theorized subdomains of executive function. DESIGN:An extensive literature search was conducted of published and unpublished materials, returning 35 studies that matched selection criteria. Meta-analysis was used to synthesize the results from studies examining the impact of OSA on executive functioning compared to controls (21 studies), and before and after treatment (19 studies); 5 studies met inclusion in both categories. MEASUREMENTS:Research papers were selected which assessed 5 subdomains of executive function: Shifting, Updating, Inhibition, Generativity, and Fluid Reasoning. RESULTS:All 5 domains of executive function demonstrated medium to very large impairments in OSA independent of age and disease severity. Furthermore, all subdomains of executive function demonstrated small to medium improvements with CPAP treatment. DISCUSSION:Executive function is impaired across all five domains in OSA; these difficulties improved with CPAP treatment. Age and disease severity did not moderate the effects found; however, further studies are needed to explore the extent of primary and secondary effects, and the impact of age and premorbid intellectual ability (cognitive reserve). 10.5665/sleep.2950