Showing papers on "Sleep disorder published in 2017"

Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits

Abstract: Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10-13) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10-9; waist circumference: rg = 0.20, P = 2.12 × 10-7).

Clinical manifestations of the anti-IgLON5 disease.

Abstract: Objective: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies. Methods: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques. Results: Patients9 median age was 64 years (range 46–83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16. Conclusions: Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.

A decision support system for automated identification of sleep stages from single-channel EEG signals

Abstract: A single channel EEG based automated sleep scoring method is proposed.A novel signal processing technique, namely TQWT is employed for sleep staging.We introduce bagging to classify sleep stages.Efficacy of the method is confirmed by statistical and graphical analyses.The performance of the proposed scheme, compared to the existing ones is promising. A decision support system for automated detection of sleep stages can alleviate the burden of medical professionals of manually annotating a large bulk of data, expedite sleep disorder diagnosis, and benefit research. Moreover, the implementation of a sleep monitoring device that is low-power and portable requires a reliable and successful sleep stage detection scheme. This article presents a methodology for computer-aided scoring of sleep stages using singe-channel EEG signals. EEG signal segments are first decomposed into sub-bands using tunable-Q wavelet transform (TQWT). Four statistical moments are then extracted from the resulting TQWT sub-bands. The proposed scheme exploits bootstrap aggregating (Bagging) for classification. Efficacy of the feature generation scheme is evaluated using intuitive, statistical, and Fisher criteria analyses. Furthermore, the efficacy of Bagging is evaluated using out-of-bag error analysis. Optimal choices of Bagging and TQWT parameters are explicated. The proposed methodology for automated sleep scoring is tested on the benchmark Sleep-EDF database and DREAMS Subjects database. Our methodology achieves 92.43%, 93.69%, 94.36%, 96.55%, and 99.75% accuracy for 2-state to 6-state classification of sleep stages on Sleep-EDF database. Experimental results show that the algorithmic performance of the automated sleep scoring technique presented herein achieves better performance as compared to the state-of-the-art sleep staging algorithms. Besides, the proposed scheme performs equally well for two sleep scoring standards, namely AASM and R&K. Moreover, the proposed decision support system yields high success rate for identifying sleep states REM and non-REM 1. It can be anticipated that owing to its use of only one channel of EEG signal, the proposed method will be suitable for device implementation, eliminate the onus of medical professionals of annotating a large volume of recordings manually, and expedite sleep disorder diagnosis.

Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder

Abstract: Objective To assess the efficacy and safety of novel pediatric-appropriate prolonged-release melatonin minitablets (PedPRM) vs. placebo for insomnia in children with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD). Method 125 children (2-17.5 years; 96.8% ASD, 3.2% Smith-Magenis syndrome [SMS]) whose sleep failed to improve on behavioral intervention alone were randomized (1:1 ratio), double-blind, to receive PedPRM (2mg escalated to 5mg) or placebo for 13 weeks. Sleep measures included the validated caregivers' Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI). The a priori primary endpoint was SND-reported total sleep time (TST) after 13 weeks of treatment. Results The study met the primary endpoint: after 13 weeks of double-blind treatment, participants slept on average 57.5 minutes longer at night with PedPRM compared to 9.14 with placebo (adjusted mean treatment difference PedPRM–placebo -32.43 minutes; p= .034). Sleep latency (SL) decreased by 39.6 minutes on average with PedPRM and 12.5 with placebo (adjusted mean treatment difference -25.30 minutes; p= .011) without causing earlier wakeup time. Rate of participants attaining clinically meaningful responses in TST and/or SL was significantly higher with PedPRM than placebo (68.9% vs 39.3% respectively; p= .001) corresponding to number needed to treat (NNT) 3.38. Overall sleep disturbance (CSDI) tended to decrease. PedPRM was generally safe; somnolence was more commonly reported with PedPRM than placebo. Conclusion PedPRM was efficacious and safe for treatment of insomnia in children with ASD with/without ADHD and NGD. The acceptability of this pediatric formulation in a population who usually experience significant difficulties in swallowing was remarkably high.

Timed Light Therapy for Sleep and Daytime Sleepiness Associated With Parkinson Disease: A Randomized Clinical Trial.

Abstract: Importance Impaired sleep and alertness are some of the most common nonmotor manifestations of Parkinson disease (PD) and currently have only limited treatment options. Light therapy (LT), a widely available treatment modality in sleep medicine, has not been systematically studied in the PD population. Objective To determine the safety and efficacy of LT on excessive daytime sleepiness (EDS) associated with PD. Design, Settings, and Participants This randomized, placebo-controlled, clinical intervention study was set in PD centers at Northwestern University and Rush University. Participants were 31 patients with PD receiving stable dopaminergic therapy with coexistent EDS, as assessed by an Epworth Sleepiness Scale score of 12 or greater, and without cognitive impairment or primary sleep disorder. Participants were randomized 1:1 to receive bright LT or dim-red LT (controlled condition) twice daily in 1-hour intervals for 14 days. This trial was conducted between March 1, 2007, and October 31, 2012. Data analysis of the intention-to-treat population was conducted from November 1, 2012, through April 30, 2016. Main Outcomes and Measures The primary outcome measure was the change in the Epworth Sleepiness Scale score comparing the bright LT with the dim-red LT. Secondary outcome measures included the Pittsburgh Sleep Quality Index score, the Parkinson’s Disease Sleep Scale score, the visual analog scale score for daytime sleepiness, and sleep log–derived and actigraphy-derived metrics. Results Among the 31 patients (13 males and 18 females; mean [SD] disease duration, 5.9 [3.6] years), bright LT resulted in significant improvements in EDS, as assessed by the Epworth Sleepiness Scale score (mean [SD], 15.81 [3.10] at baseline vs 11.19 [3.31] after the intervention). Both bright LT and dim-red LT were associated with improvements in sleep quality as captured by mean (SD) scores on the Pittsburg Sleep Quality Index (7.88 [4.11] at baseline vs 6.25 [4.27] after bright LT, and 8.87 [2.83] at baseline vs 7.33 [3.52] after dim-red LT) and the Parkinson’s Disease Sleep Scale (97.24 [22.49] at baseline vs 106.98 [19.37] after bright LT, and 95.11 [19.86] at baseline vs 99.28 [16.94] after dim-red LT). Bright LT improved several self-reported mean (SD) sleep metrics, including sleep fragmentation (number of overnight awakenings, 1.51 [1.03] at baseline vs 0.92 [0.97] after the intervention), sleep quality (sleep diary score, 3.03 [1.01] at baseline vs 3.53 [0.91] after the intervention), and ease of falling asleep (sleep diary score, 2.32 [0.89] at baseline vs 1.83 [0.88] after the intervention). Light therapy was associated with increased daily physical activity as assessed by actigraphy (average activity [SD] counts, 165.01 [66.87] at baseline vs 194.59 [87.81] after the intervention). Conclusions and Relevance Light therapy was well tolerated and may be a feasible intervention for improving the sleep-wake cycles in patients with PD. Further studies are required to determine optimal parameters of LT for PD. Trial Registration clinicaltrials.gov Identifier:NCT01338649

Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer’s Disease Biomarkers Changes

Abstract: 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 beta-amyloid 42, 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 A beta 42 concentrations, higher CSF lactate levels, and higher t-tau/A beta 42 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 Aa 42 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 A beta 42 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.

Sleep Disturbance after Hospitalization and Critical Illness: A Systematic Review.

Abstract: Rationale: Sleep disturbance during intensive care unit (ICU) admission is common and severe. Sleep disturbance has been observed in survivors of critical illness even after transfer out of the ICU. Not only is sleep important to overall health and well being, but patients after critical illness are also in a physiologically vulnerable state. Understanding how sleep disturbance impacts recovery from critical illness after hospital discharge is therefore clinically meaningful.Objectives: This Systematic Review aimed to summarize studies that identify the prevalence of and risk factors for sleep disturbance after hospital discharge for critical illness survivors.Data Sources: PubMed (January 4, 2017), MEDLINE (January 4, 2017), and EMBASE (February 1, 2017).Data Extraction: Databases were searched for studies of critically ill adult patients after hospital discharge, with sleep disturbance measured as a primary outcome by standardized questionnaire or objective measurement tools. From each relevant study, w...

Sleep disorders in the elderly: Diagnosis and management

Abstract: Compared with younger people, elderly people show age-related sleep changes, including an advanced sleep phase and decreased slow-wave sleep, which result in fragmented sleep and early awakening. Multiple etiologies contribute to insomnia in the elderly, consistent with the observation that elderly people are likely to have comorbid conditions and medications. When elderly individuals complain of insomnia, it is important to assess treatable medical conditions and medication use that may be responsible for the insomnia before the use of hypnotics is initiated. Also, screening for primary sleep disorders, such as sleep apnea syndrome, restless legs syndrome and rapid eye movement sleep behavior disorder, is essential. We review sleep disorders commonly observed in the elderly and describe their diagnosis and management.

Sleep Disturbance, Cognitive Decline, and Dementia: A Review.

Abstract: Approximately half of older people report sleep disturbances, which are associated with various health conditions, including neurodegenerative disease and dementia. Indeed, 60 to 70% of people with cognitive impairment or dementia have sleep disturbances, which are linked to poorer disease prognosis. Sleep disturbances in people with dementia have long been recognized and studied; however, in the past 10 years, researchers have begun to study disturbed sleep, including sleep fragmentation, abnormal sleep duration, and sleep disorders, as risk factors for dementia. In this review the authors summarize evidence linking sleep disturbance and dementia. They describe how specific aspects of sleep (e.g., quality, duration) and the prevalence of clinical sleep disorders (e.g., sleep-disordered breathing, rapid eye movement sleep behavior disorder) change with age; how sleep parameters and sleep disorders are associated with the risk of dementia; how sleep can be disturbed in dementia; and how disturbed sleep affects dementia prognosis. These findings highlight the potential importance of identifying and treating sleep problems and disorders in middle-aged and older adults as a strategy to prevent cognitive decline and dementia. The authors also review recent evidence linking sleep disturbances to the pathophysiology underlying dementing conditions, and briefly summarize available treatments for sleep disorders in people with dementia.

REM Sleep Behavior Disorder in Parkinson's Disease and Other Synucleinopathies

Abstract: Rapid eye movement sleep behavior disorder is characterized by dream enactment and complex motor behaviors during rapid eye movement sleep and rapid eye movement sleep atonia loss (rapid eye movement sleep without atonia) during polysomnography. Rapid eye movement sleep behavior disorder may be idiopathic or symptomatic and in both settings is highly associated with synucleinopathy neurodegeneration, especially Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure. Rapid eye movement sleep behavior disorder frequently manifests years to decades prior to overt motor, cognitive, or autonomic impairments as the presenting manifestation of synucleinopathy, along with other subtler prodromal "soft" signs of hyposmia, constipation, and orthostatic hypotension. Between 35% and 91.9% of patients initially diagnosed with idiopathic rapid eye movement sleep behavior disorder at a sleep center later develop a defined neurodegenerative disease. Less is known about the long-term prognosis of community-dwelling younger patients, especially women, and rapid eye movement sleep behavior disorder associated with antidepressant medications. Patients with rapid eye movement sleep behavior disorder are frequently prone to sleep-related injuries and should be treated to prevent injury with either melatonin 3-12 mg or clonazepam 0.5-2.0 mg to limit injury potential. Further evidence-based studies about rapid eye movement sleep behavior disorder are greatly needed, both to enable accurate prognostic prediction of end synucleinopathy phenotypes for individual patients and to support the application of symptomatic and neuroprotective therapies. Rapid eye movement sleep behavior disorder as a prodromal synucleinopathy represents a defined time point at which neuroprotective therapies could potentially be applied for the prevention of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure. © 2017 International Parkinson and Movement Disorder Society.

Sleep architecture and the risk of incident dementia in the community

Abstract: Objective Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS). Methods Our sample comprised a subset of 321 FHS Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998 and who were aged over 60 years at the time of sleep assessment (mean age 67 ± 5 years, 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for a maximum of 19 years for incident dementia (mean follow-up 12 ± 5 years). Results We observed 32 cases of incident dementia; 24 were consistent with Alzheimer disease dementia. After adjustments for age and sex, lower REM sleep percentage and longer REM sleep latency were both associated with a higher risk of incident dementia. Each percentage reduction in REM sleep was associated with approximately a 9% increase in the risk of incident dementia (hazard ratio 0.91; 95% confidence interval 0.86, 0.97). The magnitude of association between REM sleep percentage and dementia was similar following adjustments for multiple covariates including vascular risk factors, depressive symptoms, and medication use, following exclusions for persons with mild cognitive impairment at baseline and following exclusions for early converters to dementia. Stages of non-REM sleep were not associated with dementia risk. Conclusions Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia.

Sleep Disturbance and Short Sleep as Risk Factors for Depression and Perceived Medical Errors in First-Year Residents.

Abstract: Study Objectives While short and poor quality sleep among training physicians has long been recognized as problematic, the longitudinal relationships among sleep, work hours, mood, and work performance are not well understood. Here, we prospectively characterize the risk of depression and medical errors based on preinternship sleep disturbance, internship-related sleep duration, and duty hours. Methods Survey data from 1215 nondepressed interns were collected at preinternship baseline, then 3 and 6 months into internship. We examined how preinternship sleep quality and internship sleep and work hours affected risk of depression at 3 months, per the Patient Health Questionnaire 9. We then examined the impact of sleep loss and work hours on depression persistence from 3 to 6 months. Finally, we compared self-reported errors among interns based on nightly sleep duration (≤6 hr vs. >6 hr), weekly work hours (<70 hr vs. ≥70 hr), and depression (non- vs. acutely vs. chronically depressed). Results Poorly sleeping trainees obtained less sleep and were at elevated risk of depression in the first months of internship. Short sleep (≤6 hr nightly) during internship mediated the relationship between sleep disturbance and depression risk, and sleep loss led to a chronic course for depression. Depression rates were highest among interns with both sleep disturbance and short sleep. Elevated medical error rates were reported by physicians sleeping ≤6 hr per night, working ≥ 70 weekly hours, and who were acutely or chronically depressed. Conclusions Sleep disturbance and internship-enforced short sleep increase risk of depression development and chronicity and medical errors. Interventions targeting sleep problems prior to and during residency hold promise for curbing depression rates and improving patient care.

Schizophrenia and sleep disorders: links, risks, and management challenges

Abstract: Schizophrenia is a major psychiatric disorder that has a massive, long-lasting negative impact on the patients as well as society. While positive symptoms (i.e., delusions and hallucinations), negative symptoms (i.e., anhedonia, social withdrawal), and cognitive impairments are traditionally considered the most prominent features of this disorder, the role of sleep and sleep disturbances has gained increasing prominence in clinical practice. Indeed, the vast majority of patients with schizophrenia report sleep abnormalities, which tend to precede illness onset and can predict an acute exacerbation of psychotic symptoms. Furthermore, schizophrenia patients often have a comorbid sleep disorder, including insomnia, obstructive sleep apnea, restless leg syndrome, or periodic limb movement disorder. Despite accumulating data, the links between sleep disorders and schizophrenia have not been thoroughly examined, in part because they are difficult to disentangle, as numerous factors contribute to their comorbidity, including medication status. Additionally, sleep disorders are often not the primary focus of clinicians treating this population, despite studies suggesting that comorbid sleep disorders carry their own unique risks, including worsening of psychotic symptoms and poorer quality of life. There is also limited information about effective management strategies for schizophrenia patients affected by significant sleep disturbances and/or sleep disorders. To begin addressing these issues, the present review will systematically examine the literature on sleep disorders and schizophrenia, focusing on studies related to 1) links between distinct sleep disorders and schizophrenia; 2) risks unique to patients with a comorbid sleep disorder; and 3) and management challenges and strategies.

Cognitive Behavioral Insomnia Therapy for Those With Insomnia and Depression: A Randomized Controlled Clinical Trial

Abstract: Study objective To compare cognitive behavioral therapy for insomnia (CBT-I) + antidepressant medication (AD) against treatments that target solely depression or solely insomnia. Design A blinded, randomized split-plot experimental study. Setting Two urban academic clinical centers. Participants 107 participants (68% female, mean age 42 ± 11) with major depressive disorder and insomnia. Interventions Randomization was to one of three groups: antidepressant (AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo pill, or AD + 4-session sleep hygiene control (SH). Measurements and results Subjective sleep was assessed via 2 weeks of daily sleep diaries (use of medication was covaried in all analyses); although there were no statistically significant group differences detected, all groups improved from baseline to posttreatment on subjective sleep efficiency (SE) and total wake time (TWT) and the effect sizes were large. Objective sleep was assessed via overnight polysomnographic monitoring at baseline and posttreatment; analyses revealed both CBT groups improved on TWT (p = .03), but the AD + SH group worsened. There was no statistically significant effect for PSG SE (p = .07). There was a between groups medium effect observed for the AD + SH and CBT + placebo group differences on diary TWT and both PSG variables. All groups improved significantly from baseline to posttreatment on the Hamilton Rating Scale for Depression (HAMD-17); the groups did not differ. Conclusions Although all groups self-reported sleeping better after treatment, only the CBT-I groups improved on objective sleep, and AD + SH's sleep worsened. This suggests that we should be treating sleep in those with depression with an effective insomnia treatment and relying on self-report obscures sleep worsening effects. All groups improved on depression, even a group with absolutely no depression-focused treatment component (CBT-I + placebo). The depression effect in CBT-I only group has been reported in other studies, suggesting that we should further investigate the antidepressant properties of CBT-I.