Showing papers in "Sleep in 2017"

Sleep, Cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis.

Abstract: Study objectives Mounting evidence implicates disturbed sleep or lack of sleep as one of the risk factors for Alzheimer's disease (AD), but the extent of the risk is uncertain. We conducted a broad systematic review and meta-analysis to quantify the effect of sleep problems/disorders on cognitive impairment and AD. Methods Original published literature assessing any association of sleep problems or disorders with cognitive impairment or AD was identified by searching PubMed, Embase, Web of Science, and the Cochrane library. Effect estimates of individual studies were pooled and relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. We also estimated the population attributable risk. Results Twenty-seven observational studies (n = 69216 participants) that provided 52 RR estimates were included in the meta-analysis. Individuals with sleep problems had a 1.55 (95% CI: 1.25-1.93), 1.65 (95% CI: 1.45-1.86), and 3.78 (95% CI: 2.27-6.30) times higher risk of AD, cognitive impairment, and preclinical AD than individuals without sleep problems, respectively. The overall meta-analysis revealed that individuals with sleep problems had a 1.68 (95% CI: 1.51-1.87) times higher risk for the combined outcome of cognitive impairment and/or AD. Approximately 15% of AD in the population may be attributed to sleep problems. Conclusion This meta-analysis confirmed the association between sleep and cognitive impairment or AD and, for the first time, consolidated the evidence to provide an "average" magnitude of effect. As sleep problems are of a growing concern in the population, these findings are of interest for potential prevention of AD.

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.

Genetic Basis of Chronotype in Humans: Insights From Three Landmark GWAS

Abstract: Study objectives Chronotype, or diurnal preference, refers to behavioral manifestations of the endogenous circadian system that governs preferred timing of sleep and wake. As variations in circadian timing and system perturbations are linked to disease development, the fundamental biology of chronotype has received attention for its role in the regulation and dysregulation of sleep and related illnesses. Family studies indicate that chronotype is a heritable trait, thus directing attention toward its genetic basis. Although discoveries from molecular studies of candidate genes have shed light onto its genetic architecture, the contribution of genetic variation to chronotype has remained unclear with few related variants identified. In the advent of large-scale genome-wide association studies (GWAS), scientists now have the ability to discover novel common genetic variants associated with complex phenotypes. Three recent large-scale GWASs of chronotype were conducted on subjects of European ancestry from the 23andMe cohort and the UK Biobank. This review discusses the findings of these landmark GWASs in the context of prior research. Methods We systematically reviewed and compared methodological and analytical approaches and results across the three GWASs of chronotype. Results A good deal of consistency was observed across studies with 9 genes identified in 2 of the 3 GWASs. Several genes previously unknown to influence chronotype were identified. Conclusions GWAS is an important tool in identifying common variants associated with the complex chronotype phenotype, the findings of which can supplement and guide molecular science. Future directions in model systems and discovery of rare variants are discussed.

Sleep-Wake Disturbances After Traumatic Brain Injury: Synthesis of Human and Animal Studies.

Abstract: Sleep-wake disturbances following traumatic brain injury (TBI) are increasingly recognized as a serious consequence following injury and as a barrier to recovery. Injury-induced sleep-wake disturbances can persist for years, often impairing quality of life. Recently, there has been a nearly exponential increase in the number of primary research articles published on the pathophysiology and mechanisms underlying sleep-wake disturbances after TBI, both in animal models and in humans, including in the pediatric population. In this review, we summarize over 200 articles on the topic, most of which were identified objectively using reproducible online search terms in PubMed. Although these studies differ in terms of methodology and detailed outcomes; overall, recent research describes a common phenotype of excessive daytime sleepiness, nighttime sleep fragmentation, insomnia, and electroencephalography spectral changes after TBI. Given the heterogeneity of the human disease phenotype, rigorous translation of animal models to the human condition is critical to our understanding of the mechanisms and of the temporal course of sleep-wake disturbances after injury. Arguably, this is most effectively accomplished when animal and human studies are performed by the same or collaborating research programs. Given the number of symptoms associated with TBI that are intimately related to, or directly stem from sleep dysfunction, sleep-wake disorders represent an important area in which mechanistic-based therapies may substantially impact recovery after TBI.

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.

Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder

Abstract: Objectives.: REM sleep behaviour disorder (RBD) is the most specific marker of prodromal alpha-synucleinopathies. We sought to delineate the baseline clinical characteristics of RBD and evaluate risk stratification models. Methods.: Clinical assessments were performed in 171 RBD, 296 control and 119 untreated Parkinson's (PD) subjects. Putative risk measures were assessed as predictors of prodromal neurodegeneration and Movement Disorders Society (MDS) criteria for prodromal PD were applied. Participants were screened for common LRRK2/GBA gene mutations. Results.: Compared to controls, RBD subjects had higher rates of solvent exposure, head injury, smoking, obesity and antidepressant use. GBA mutations were more common in RBD, but no LRRK2 mutations were found. RBD subjects performed significantly worse than controls on UPDRS-III, timed 'get-up-and-go', Flamingo test, Sniffin Sticks and cognitive tests, and had worse measures of constipation, quality of life and orthostatic hypotension. For all these measures except UPDRS-III, RBD and PD subjects were equally impaired. Depression, anxiety and apathy were worse in RBD compared to PD subjects. Stratification of RBD patients according to antidepressant use, obesity and age altered the odds ratio of hyposmia compared to controls from 3.4 to 45.5. 74% (95% CI 66%, 80%) of RBD subjects met the MDS criteria for probable prodromal Parkinson's compared to 0.3% (95% CI 0.009%, 2%) of controls. Conclusions.: RBD subjects are impaired across a range of clinical measures consistent with prodromal PD and suggestive of a more severe non-motor subtype. Clinical risk stratification has the potential to select higher risk patients for neuroprotective interventions.

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.

Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep.

Abstract: Introduction Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves. Aims Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use. Methods Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented. Results Results showed that the sound stimulation increased both slow wave (p = .002) and sleep spindle activity (p < .001). When overnight improvement of memory performance was compared between stimulus and control nights, we found a significant effect in word pair task but not in other memory tasks. The stimulation did not affect sleep structure or subjective sleep quality. Conclusions We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future.

Validation of Photoplethysmography-Based Sleep Staging Compared With Polysomnography in Healthy Middle-Aged Adults.

Abstract: Study objectives To compare the accuracy of automatic sleep staging based on heart rate variability measured from photoplethysmography (PPG) combined with body movements measured with an accelerometer, with polysomnography (PSG) and actigraphy. Methods Using wrist-worn PPG to analyze heart rate variability and an accelerometer to measure body movements, sleep stages and sleep statistics were automatically computed from overnight recordings. Sleep-wake, 4-class (wake/N1 + N2/N3/REM) and 3-class (wake/NREM/REM) classifiers were trained on 135 simultaneously recorded PSG and PPG recordings of 101 healthy participants and validated on 80 recordings of 51 healthy middle-aged adults. Epoch-by-epoch agreement and sleep statistics were compared with actigraphy for a subset of the validation set. Results The sleep-wake classifier obtained an epoch-by-epoch Cohen's κ between PPG and PSG sleep stages of 0.55 ± 0.14, sensitivity to wake of 58.2 ± 17.3%, and accuracy of 91.5 ± 5.1%. κ and sensitivity were significantly higher than with actigraphy (0.40 ± 0.15 and 45.5 ± 19.3%, respectively). The 3-class classifier achieved a κ of 0.46 ± 0.15 and accuracy of 72.9 ± 8.3%, and the 4-class classifier, a κ of 0.42 ± 0.12 and accuracy of 59.3 ± 8.5%. Conclusions The moderate epoch-by-epoch agreement and, in particular, the good agreement in terms of sleep statistics suggest that this technique is promising for long-term sleep monitoring, although more evidence is needed to understand whether it can complement PSG in clinical practice. It also offers an improvement in sleep/wake detection over actigraphy for healthy individuals, although this must be confirmed on a larger, clinical population.

Loop Gain Predicts the Response to Upper Airway Surgery in Patients With Obstructive Sleep Apnea.

Abstract: Upper airway surgery is often recommended to treat patients with obstructive sleep apnea (OSA) who cannot tolerate continuous positive airways pressure However, the response to surgery is variable, potentially because it does not improve the nonanatomical factors (ie, loop gain [LG] and arousal threshold) causing OSA Measuring these traits clinically might predict responses to surgery Our primary objective was to test the value of LG and arousal threshold to predict surgical success defined as 50% reduction in apnea-hypopnea index (AHI) and AHI We retrospectively analyzed data from patients who underwent upper airway surgery for OSA (n = 46) Clinical estimates of LG and arousal threshold were calculated from routine polysomnographic recordings presurgery and postsurgery (median of 124 [91-170] days follow-up) Surgery reduced both the AHI (391 ± 42 vs 265 ± 36 events/hour; p Our study provides proof-of-principle that upper airway surgery most effectively resolves OSA in patients with lower LG Predicting the failure of surgical treatment, consequent to less stable ventilatory control (elevated LG), can be achieved in the clinic and may facilitate avoidance of surgical failures

REM Sleep Behavior Disorder and Cognitive Impairment in Parkinson's Disease.

Abstract: Study Objectives REM sleep behavior disorder (RBD) is a parasomnia affecting 33% to 46% of patients with Parkinson's disease (PD). The existence of a unique and specific impaired cognitive profile in PD patients with RBD is still controversial. We extensively assessed cognitive functions to identify whether RBD is associated with more severe cognitive deficits in nondemented patients with PD. Methods One hundred sixty-two participants, including 53 PD patients with RBD, 40 PD patients without RBD, and 69 healthy subjects, underwent polysomnography, a neurological assessment and an extensive neuropsychological exam to assess attention, executive functions, episodic learning and memory, visuospatial abilities, and language. Results PD patients with RBD had poorer and clinically impaired performance in several cognitive tests compared to PD patients without RBD and healthy subjects. These two latter groups were similar on all cognitive measures. Mild cognitive impairment (MCI) diagnosis frequency was almost threefold higher in PD patients with RBD compared to PD patients without RBD (66% vs. 23%, p < .001). Moreover, subjective cognitive decline was reported in 89% of PD patients with RBD compared to 58% of PD patients without RBD (p = .024). Conclusions RBD in PD is associated with a more impaired cognitive profile and higher MCI diagnosis frequency, suggesting more severe and widespread neurodegeneration. This patient subgroup and their caregivers should receive targeted medical attention to better detect and monitor impairment and to enable the development of management interventions for cognitive decline and its consequences.

Sleep Quality and Nocturnal Sleep Duration in Pregnancy and Risk of Gestational Diabetes Mellitus

Abstract: Study Objectives To examine the influence of maternal sleep quality and nocturnal sleep duration on risk of gestational diabetes mellitus (GDM) in a multiethnic Asian population. Methods A cohort of 686 women (376 Chinese, 186 Malay, and 124 Indian) with a singleton pregnancy attended a clinic visit at 26-28 weeks of gestation as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). GDM was diagnosed based on a 75-g oral glucose tolerance test administered after an overnight fast (1999 WHO criteria). Multiple logistic regression was used to model separately the associations of poor sleep quality (PSQI score > 5) and short nocturnal sleep duration (<6 h) with GDM, adjusting for age, ethnicity, maternal education, body mass index, previous history of GDM, and anxiety (State-Trait Anxiety Inventory score). Results In the cohort 296 women (43.1%) had poor sleep quality and 77 women (11.2%) were categorized as short sleepers; 131 women (19.1%) were diagnosed with GDM. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of GDM (poor sleep, adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.11 to 2.76; short sleep, adjusted OR = 1.96, 95% CI 1.05 to 3.66). Conclusions During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibited abnormal glucose regulation. Treating sleep problems and improving sleep behavior in pregnancy could potentially reduce the risk and burden of GDM.

Risk of motor vehicle accidents related to sleepiness at the wheel: a systematic review and meta-analysis

Abstract: Study objectives Sleepiness at the wheel is widely believed to be a cause of motor vehicle accidents. Nevertheless, a systematic review of studies investigating this relationship has not yet been published. The objective of this study was to quantify the relationship between sleepiness at the wheel and motor vehicle accidents. Methods A systematic review was performed using Medline, Scopus, and ISI Web of Science. The outcome measure of interest was motor vehicle accident defined as involving four- or two-wheeled vehicles in road traffic, professional and nonprofessional drivers, with or without objective consequences. The exposure was sleepiness at the wheel defined as self-reported sleepiness at the wheel. Studies were included if they provided adjusted risk estimates of motor vehicle accidents related to sleepiness at the wheel. Risk estimates and 95% confidence intervals (95% CIs) were extracted and pooled as odds ratios (ORs) using a random-effect model. Heterogeneity was quantified using Q statistics and the I2 index. The potential causes of heterogeneity were investigated using meta-regressions. Results Ten cross-sectional studies (51,520 participants), six case-control studies (4904 participants), and one cohort study (13,674 participants) were included. Sleepiness at the wheel was associated with an increased risk of motor vehicle accidents (pooled OR 2.51 [95% CI 1.87; 3.39]). A significant heterogeneity was found between the individual risk estimates (Q = 93.21; I2 = 83%). Conclusions Sleepiness at the wheel increases the risk of motor vehicle accidents and should be considered when investigating fitness to drive. Further studies are required to explore the nature of this relationship. Systematic review registration number PROSPERO 2015 CRD42015024805.

Insomnia, Sleep Duration, Depressive Symptoms, and the Onset of Chronic Multisite Musculoskeletal Pain.

Abstract: Study objective: The temporal relationships among sleep, depressive symptoms, and pain are unclear. This longitudinal study examines whether insomnia and sleep duration predict the onset of chronic multisite musculoskeletal pain over 6 years and whether this association is mediated by depressive symptoms. Methods: 1860 subjects of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were followed up for the onset of chronic multisite musculoskeletal pain over 6 years (Chronic Pain Grade Questionnaire). We determined baseline insomnia (Women's Health Initiative Insomnia Rating Scale ≥9) and sleep duration (short: ≤6 hr, normal: 7-9 hr, long: ≥10 hr). Depressive symptoms were assessed at baseline and as a change score over time (Inventory of Depressive Symptomatology). Results: Insomnia (hazard ratio [HR] [95% confidence interval, 95%CI] = 1.60 [1.30-1.96], p < .001) and short sleep duration (HR [95%CI] = 1.52 [1.22-1.90], p < .001) were associated with chronic pain onset. Adding baseline depressive symptoms as a mediator attenuated the associations for insomnia and short sleep with chronic pain onset (∆B = 40% and 26%, respectively). Adding the change score of depressive symptoms further weakened the association for insomnia (∆B = 16%) but not for short sleep. All direct effects for sleep measures with chronic pain onset remained statistically significant (p < .05). Conclusions: This longitudinal study shows that insomnia and short sleep duration are risk factors for developing chronic pain. Depressive symptoms partially mediate the effect for insomnia and short sleep with developing chronic pain.

REM Sleep EEG Instability in REM Sleep Behavior Disorder and Clonazepam Effects.

Abstract: Study Objectives We aimed to analyze quantitatively rapid eye movement (REM) sleep electroencephalogram (EEG) in controls, drug-naive idiopathic REM sleep behavior disorder patients (iRBD), and iRBD patients treated with clonazepam. Methods Twenty-nine drug-naive iRBD patients (mean age 68.2 years), 14 iRBD patients under chronic clonazepam therapy (mean age 66.3 years), and 21 controls (mean age 66.8 years) were recruited. Power spectra were obtained from sleep EEG (central derivation), using a 2-second sliding window, with 1-second steps. The power values of each REM sleep EEG spectral band (one every second) were normalized with respect to the average power value obtained during sleep stage 2 in the same individual. Results In drug-naive patients, the normalized power values showed a less pronounced REM-related decrease of power in all bands with frequency <15 Hz than controls and an increase in the beta band, negatively correlated with muscle atonia; in patients treated with clonazepam there was a partial return of all bands <15 Hz toward the control values. The standard deviation values of the normalized power were higher for untreated patients in all EEG bands and were almost completely normalized in patients treated with clonazepam. Conclusions The REM sleep EEG structure changes found in this study disclose subtle but significant alterations in the cortical electrophysiology of RBD that might represent the early expression of the supposed neurodegenerative processes already taking place at this stage of the disease and might be the target of better and effective future therapeutic strategies for this condition.

Linking light exposure and subsequent sleep : A field polysomnography study in humans

Abstract: Study objectives To determine the effect of light exposure on subsequent sleep characteristics under ambulatory field conditions. Methods Twenty healthy participants were fitted with ambulatory polysomnography (PSG) and wrist-actigraphs to assess light exposure, rest-activity, sleep quality, timing, and architecture. Laboratory salivary dim-light melatonin onset was analyzed to determine endogenous circadian phase. Results Later circadian clock phase was associated with lower intensity (R2 = 0.34, χ2(1) = 7.19, p < .01), later light exposure (quadratic, controlling for daylength, R2 = 0.47, χ2(3) = 32.38, p < .0001), and to later sleep timing (R2 = 0.71, χ2(1) = 20.39, p < .0001). Those with later first exposure to more than 10 lux of light had more awakenings during subsequent sleep (controlled for daylength, R2 = 0.36, χ2(2) = 8.66, p < .05). Those with later light exposure subsequently had a shorter latency to first rapid eye movement (REM) sleep episode (R2 = 0.21, χ2(1) = 5.77, p < .05). Those with less light exposure subsequently had a higher percentage of REM sleep (R2 = 0.43, χ2(2) = 13.90, p < .001) in a clock phase modulated manner. Slow-wave sleep accumulation was observed to be larger after preceding exposure to high maximal intensity and early first light exposure (p < .05). Conclusions The quality and architecture of sleep is associated with preceding light exposure. We propose that light exposure timing and intensity do not only modulate circadian-driven aspects of sleep but also homeostatic sleep pressure. These novel ambulatory PSG findings are the first to highlight the direct relationship between light and subsequent sleep, combining knowledge of homeostatic and circadian regulation of sleep by light. Upon confirmation by interventional studies, this hypothesis could change current understanding of sleep regulation and its relationship to prior light exposure. Clinical trial details This study was not a clinical trial. The study was ethically approved and nationally registered (NL48468.042.14).

Insomnia Patients With Objective Short Sleep Duration Have a Blunted Response to Cognitive Behavioral Therapy for Insomnia.

Abstract: Study Objectives This study examined whether individuals with insomnia and objective short sleep duration 80%; χ2[1, N = 60] = 21, p 50% decline in MWASO (χ2[1, N = 60] = 60, p < .0001) compared to individuals with insomnia and short sleep duration. Additionally, those with insomnia and normal sleep duration had more success decreasing their total wake time (TWT) at the 6-month follow-up compared to those with insomnia and short sleep duration (χ2[2, N = 60] = 44.1, p < .0001). Receiver-operating characteristic curve analysis found that using a 6-h cutoff with actigraphy provided a 95.7% sensitivity and 91.9% specificity for determining insomnia remission, with the area under the curve = 0.986. Conclusions Findings suggest that individuals with insomnia and objective short sleep duration <6 h are significantly less responsive to CBT-I than those with insomnia and normal sleep duration ≥6 h. Using an actigraphy TST cutoff of 6 hours to classify sleep duration groups was highly accurate and provided good discriminant value for determining insomnia remission.

Test-Retest Reliability of the Multiple Sleep Latency Test in Central Disorders of Hypersomnolence.

Abstract: Study objectives To assess the test-retest reliability of the polysomnography-multiple sleep latency test (PSG-MSLT) diagnostic classification and measures and to study the determinants of its variability in patients with narcolepsy type 1 (NT1) or with noncataplectic central disorders of hypersomnolence (NCHS): type 2 (NT2), idiopathic hypersomnia (IH), and unspecified hypersomnolence (unspecified excessive daytime sleepiness [UnsEDS]). Methods PSG-MSLT in drug-free conditions was administered twice (median interval of 1.9 years) in 22 patients with NT1 (10 males, median age 31.2 years) and 75 patients with NCHS (32 males, median age 25.7 years). Results At the first PSG-MSLT, patients with NCHS were classified as having NT2 (22.7%), IH (26.7%), or UnsEDS (50.6%). A positive PSG-MSLT was confirmed in 72.7% of NT1. The classification consistency at retesting was significantly lower for the NT2 (47.1%), IH (25.0%), and UnsEDS (42.1%) categories than NT1 (81.3%). The between-test mean sleep latency (MSL) variability was significantly different in NT1 and NCHS, with higher changes in NT2 and lower in NT1. A longer test-retest interval was associated with improved MSL and MSLT normalization. Between-test variations in SOREMP number were associated with changes in nocturnal REM sleep parameters and MSL. No association was found with the clinical decision to repeat the evaluation or the disease clinical course. Conclusion The PSG-MSLT measures and classification are not stable in patients with NCHS, with frequent diagnostic changes, particularly for NT2 and IH, compared with NT1. MSLT needs to be repeated at regular intervals to confirm a stable hypersomnia and provide an accurate diagnosis of NT2 and IH.

Large-Scale Automated Sleep Staging.

Abstract: Study objectives Automated sleep staging has been previously limited by a combination of clinical and physiological heterogeneity. Both factors are in principle addressable with large data sets that enable robust calibration. However, the impact of sample size remains uncertain. The objectives are to investigate the extent to which machine learning methods can approximate the performance of human scorers when supplied with sufficient training cases and to investigate how staging performance depends on the number of training patients, contextual information, model complexity, and imbalance between sleep stage proportions. Methods A total of 102 features were extracted from six electroencephalography (EEG) channels in routine polysomnography. Two thousand nights were partitioned into equal (n = 1000) training and testing sets for validation. We used epoch-by-epoch Cohen's kappa statistics to measure the agreement between classifier output and human scorer according to American Academy of Sleep Medicine scoring criteria. Results Epoch-by-epoch Cohen's kappa improved with increasing training EEG recordings until saturation occurred (n = ~300). The kappa value was further improved by accounting for contextual (temporal) information, increasing model complexity, and adjusting the model training procedure to account for the imbalance of stage proportions. The final kappa on the testing set was 0.68. Testing on more EEG recordings leads to kappa estimates with lower variance. Conclusion Training with a large data set enables automated sleep staging that compares favorably with human scorers. Because testing was performed on a large and heterogeneous data set, the performance estimate has low variance and is likely to generalize broadly.

Social Media Use Before Bed and Sleep Disturbance Among Young Adults in the United States: A Nationally Representative Study.

Abstract: Study objectives Social media (SM) use has been positively associated with disturbed sleep among young adults. However, previous studies have not elucidated the specific importance of SM use immediately before bed. We aimed to determine the independent association of SM use during the 30 minutes before bed and disturbed sleep while controlling for covariates including total SM use throughout the day. Methods We assessed a nationally representative sample of 1763 US young adults aged 19-32. Participants estimated to what extent they used SM in the 30 minutes before bed. We assessed sleep disturbance using the brief Patient-Reported Outcomes Measurement Information System (PROMIS®) Sleep Disturbance measure. After testing the proportional odds assumption, we used ordered logistic regression to compute the independent association between SM use before bed and sleep disturbance controlling for covariates, including total SM use. Results Compared with those who rarely or very rarely check SM in the 30 minutes before bed, those who often or very often check SM at that time had an adjusted odds ratio of 1.62 (95% confidence interval = 1.31-2.34) for increased sleep disturbance. Additionally, we found a significant linear trend in the odds ratios between the frequency of checking SM in the 30 minutes before bed and increased sleep disturbance (p = .007). Results were consistent in all sensitivity analyses. Conclusions SM use in the 30 minutes before bed is independently associated with disturbed sleep among young adults. Future work should use qualitative and experimental methods to further elucidate the directionality of-and mechanisms underlying-this association.

The Neighborhood Social Environment and Objective Measures of Sleep in the Multi-Ethnic Study of Atherosclerosis

Abstract: Study objectives To investigate cross-sectional associations of neighborhood social environment (social cohesion, safety) with objective measures of sleep duration, timing, and disturbances Methods A racially/ethnically diverse population of men and women (N = 1949) aged 54 to 93 years participating in the Multi-Ethnic Study of Atherosclerosis Sleep and Neighborhood Ancillary studies Participants underwent 1-week actigraphy between 2010 and 2013 Measures of sleep duration, timing, and disruption were averaged over all days Neighborhood characteristics were assessed via questionnaires administered to participants and an independent sample within the same neighborhood and aggregated at the neighborhood (census tract, N = 783) level using empirical Bayes estimation Multilevel linear regression models were used to assess the association between the neighborhood social environment and each sleep outcome Results Neighborhood social environment characterized by higher levels of social cohesion and safety were associated with longer sleep duration and earlier sleep midpoint Each 1 standard deviation higher neighborhood social environment score was associated with 61 minutes longer [95% confidence interval (CI): 20, 102] sleep duration and 64 minutes earlier (CI: 22, 106) sleep midpoint after adjustment for age, sex, race, socioeconomic status, and marital status These associations persisted after adjustment for other risk factors Neighborhood social factors were not associated with sleep efficiency or sleep fragmentation index Conclusions A more favorable neighborhood social environment is associated with longer objectively measured sleep duration and earlier sleep timing Intervening on the neighborhood environment may improve sleep and subsequent health outcomes

Prevalence of Circadian Misalignment and Its Association with Depressive Symptoms in Delayed Sleep Phase Disorder.

Abstract: Study Objective: To examine the prevalence of circadian misalignment in clinically diagnosed delayed sleep phase disorder (DSPD) and to compare mood and daytime functioning in those with and without a circadian basis for the disorder. Methods: One hundred and eighty-two DSPD patients aged 16-64 years, engaged in regular employment or school, underwent sleep-wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime (DBT), or non-circadian DSPD, defined as DLMO occurring before DBT. Results: One hundred and three patients (57%) were classified as circadian DSPD and 79 (43%) as non-circadian DSPD. DLMO occurred 1.66 hours later in circadian DSPD compared to non-circadian DSPD (p < .001). Moderate-severe depressive symptoms (Beck Depression Inventory-II) were more prevalent in circadian DSPD (14.0%) than in non-circadian DSPD (3.8%; p < .05). Relative to non-circadian DSPD patients, circadian DSPD patients had 4.31 times increased odds of at least mild depressive symptoms (95% CI 1.75 to 10.64; p < .01). No group differences were found for daytime sleepiness or function, but DSPD symptoms were rated by clinicians to be more severe in those with circadian DSPD. Conclusions: Almost half of patients clinically diagnosed with DSPD did not show misalignment between the circadian pacemaker and the DBT, suggesting that the reported difficulties initiating sleep at the DBT are unlikely to be explained by the (mis)timing of the circadian rhythm of sleep propensity. Circadian misalignment in DSPD is associated with increased depressive symptoms and DSPD symptom severity.

Short Sleep Duration Increases Metabolic Impact in Healthy Adults: A Population-Based Cohort Study.

Abstract: Objectives The metabolic impact of inadequate sleep has not been determined in healthy individuals outside laboratories. This study aims to investigate the impact of sleep duration on five metabolic syndrome components in a healthy adult cohort. Methods A total of 162121 adults aged 20-80 years (men 47.4%) of the MJ Health Database, who were not obese and free from major diseases, were recruited and followed up from 1996 to 2014. Sleep duration and insomnia symptoms were assessed by a self-administered questionnaire. Incident cases of five metabolic syndrome components were identified by follow-up medical examinations. Cox proportional hazard ratios (HRs) were calculated for three sleep duration categories " 8 hours/day (long)" with adjustment for potential confounding factors. Analyses were stratified by insomnia symptoms to assess whether insomnia symptoms modified the association between sleep duration and metabolic syndrome. Results Compared to regular sleep duration, short sleep significantly (p < .001) increased the risk for central obesity by 12% (adjusted HR 1.12 [1.07-1.17]), for elevated fasting glucose by 6% (adjusted HR 1.06 [1.03-1.09]), for high blood pressure by 8% (adjusted HR 1.08 [1.04-1.13]), for low high-density lipoprotein-cholesterol by 7% (adjusted HR 1.07 [1.03-1.11]), for hypertriglyceridemia by 9% (adjusted HR 1.09 [1.05-1.13]), and for metabolic syndrome by 9% (adjusted HR 1.09 [1.05-1.13]). Long sleep decreased the risk of hypertriglyceridemia (adjusted HR 0.89 [0.84-0.94]) and metabolic syndrome (adjusted HR 0.93 [0.88-0.99]). Insomnia symptoms did not modify the effects of sleep duration. Conclusions Sleep duration may be a significant determinant of metabolic health.

Mediterranean Diet and Changes in Sleep Duration and Indicators of Sleep Quality in Older Adults

Abstract: Study Objective To examine the association between adherence to a Mediterranean diet (MD) and changes in sleep duration and sleep quality in older adults. Methods We used data from 1596 participants in the Seniors-ENRICA cohort aged ≥ 60 years. MD was evaluated in 2012 with the Mediterranean Diet Adherence Screener (MEDAS) score. Sleep duration (h) and indicators of poor sleep quality were assessed both in 2012 and 2015. Analyses were adjusted for sociodemographic, lifestyle and morbidity variables, and for sleep duration and the number of poor sleep indicators at baseline. Results Over a median follow-up of 2.8 years, 12.2% of individuals increased and 8.8% decreased their sleep duration by ≥2 h/night. Compared with those in the lowest tertile of adherence to the MD in 2012, those in the highest tertile showed both a lower risk of a ≥2 h/night increase in sleep duration (odds ratio [OR]: 0.54, 95% confidence interval [CI] 0.34-0.85, p-trend = .01) and of a ≥2 h/night decrease (OR: 0.58, 95% CI 0.35-0.95, p-trend = 0.02) from 2012 to 2015. Being in the highest tertile of MD in 2012 was also associated with lower risk of poor sleep quality at follow-up, the OR (95% CI) for having 2-3 indicators of poor sleep was 0.70 (0.51-0.97) and for ≥4 indicators was 0.68 (0.47-0.99, p-trend = .04). High adherence to the MD was also associated with 56% lower odds of having large changes in sleep duration and ≥2 indicators of poor sleep quality simultaneously (OR: 0.44, 95% CI 0.29-0.68, p trend < .001). Conclusions Adherence to a MD pattern was associated with lower risk of changes in sleep duration and with better sleep quality in older adults.

Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia.

Abstract: Study objectives Schizophrenia patients have correlated deficits in sleep spindle density and sleep-dependent memory consolidation. In addition to spindle density, memory consolidation is thought to rely on the precise temporal coordination of spindles with slow waves (SWs). We investigated whether this coordination is intact in schizophrenia and its relation to motor procedural memory consolidation. Methods Twenty-one chronic medicated schizophrenia patients and 17 demographically matched healthy controls underwent two nights of polysomnography, with training on the finger tapping motor sequence task (MST) on the second night and testing the following morning. We detected SWs (0.5-4 Hz) and spindles during non-rapid eye movement (NREM) sleep. We measured SW-spindle phase-amplitude coupling and its relation with overnight improvement in MST performance. Results Patients did not differ from controls in the timing of SW-spindle coupling. In both the groups, spindles peaked during the SW upstate. For patients alone, the later in the SW upstate that spindles peaked and the more reliable this phase relationship, the greater the overnight MST improvement. Regression models that included both spindle density and SW-spindle coordination predicted overnight improvement significantly better than either parameter alone, suggesting that both contribute to memory consolidation. Conclusion Schizophrenia patients show intact spindle-SW temporal coordination, and these timing relationships, together with spindle density, predict sleep-dependent memory consolidation. These relations were seen only in patients suggesting that their memory is more dependent on optimal spindle-SW timing, possibly due to reduced spindle density. Interventions to improve memory may need to increase spindle density while preserving or enhancing the coordination of NREM oscillations.

Neurobehavioral Impact of Successive Cycles of Sleep Restriction With and Without Naps in Adolescents

Abstract: Study objectives To characterize adolescents' neurobehavioral changes during two cycles of restricted and recovery sleep and to examine the effectiveness of afternoon naps in ameliorating neurobehavioral deficits associated with multiple nights of sleep restriction. Methods Fifty-seven healthy adolescents (aged 15-19 years; 31 males) participated in a parallel group study. They underwent two cycles of sleep restriction (5-hr time in bed [TIB] for five and three nights in the first and the second cycles, respectively; 01:00-06:00) and recovery (9-hr TIB for two nights per cycle; 23:00-08:00) intended to simulate the weekday sleep loss and weekend attempt to "catch up" on sleep. Half of the participants received a 1-hr nap opportunity at 14:00 following each sleep-restricted night, while the other half stayed awake. Sustained attention, sleepiness, speed of processing, executive function, and mood were assessed 3 times each day. Results Participants who were not allowed to nap showed progressive decline in sustained attention that did not return to baseline after two nights of recovery sleep. Exposure to the second period of sleep restriction increased the rate of vigilance deterioration. Similar patterns were found for other neurobehavioral measures. Napping attenuated but did not eliminate performance decline. These findings contrasted with the stable performance of adolescents, given 9-hr TIB each night in our recent study. Conclusions Adolescents' neurobehavioral functions may not adapt to successive cycles of sleep curtailment and recovery. In sleep-restricted adolescents, weekend "catch-up sleep," even when combined with napping during weekdays, is inferior to receiving a 9-hr sleep opportunity each night.

Sleep and Physiological Dysregulation: A Closer Look at Sleep Intraindividual Variability.

Abstract: Study Objectives Variable daily sleep (ie, higher intraindividual variability; IIV) is associated with negative health consequences, but potential physiological mechanisms are poorly understood. This study examined how the IIV of sleep timing, duration, and quality is associated with physiological dysregulation, with diurnal cortisol trajectories as a proximal outcome and allostatic load (AL) as a multisystem distal outcome. Methods Participants are 436 adults (Mage ± standard deviation = 54.1 ± 11.7, 60.3% women) from the Midlife in the United States study. Sleep was objectively assessed using 7-day actigraphy. Diurnal cortisol was measured via saliva samples (four/day for 4 consecutive days). AL was measured using 23 biomarkers from seven systems (inflammatory, hypothalamic–pituitary–adrenal axis, metabolic glucose and lipid, cardiovascular, parasympathetic, sympathetic) using a validated bifactor model. Linear and quadratic effects of sleep IIV were estimated using a validated Bayesian model. Results Controlling for covariates, more variable sleep timing (p = .04 for risetime, p = .097 for bedtime) and total sleep time (TST; p = .02), but not mean sleep variables, were associated with flatter cortisol diurnal slope. More variable sleep onset latency and wake after sleep onset, later average bedtime, and shorter TST were associated with higher AL adjusting for age and sex (p-values < .05); after controlling for all covariates, however, only later mean bedtime remained significantly associated with higher AL (p = .04). Conclusions In a community sample of adults, more variable sleep patterns were associated with blunted diurnal cortisol trajectories but not with higher multisystem physiological dysregulation. The associations between sleep IIV and overall health are likely complex, including multiple biopsychosocial determinants and require further investigation.

Associations of Sleep Duration and Disturbances With Hypertension in Metropolitan Cities of Delhi, Chennai, and Karachi in South Asia: Cross-Sectional Analysis of the CARRS Study

Abstract: Objectives Sleep duration and disturbances may be risk factors for hypertension. Despite the high burden of hypertension in South Asia, little is known about this relationship in this region. Methods We analyzed population-level cross-sectional data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) study that recruited representative samples of adults ≥ 20 years from three cities-Delhi, Chennai (India), and Karachi (Pakistan) during 2010-2011. We defined hypertension as self-reported treatment or measured blood pressure (BP) ≥140/90 mm Hg. Data on usual duration of sleep, insomnia, and snoring were collected using "The Sleep Habits Questionnaire" and excessive daytime sleepiness (EDS) using Epworth Sleepiness Score. Logistic and linear regression were done with hypertension and BP as outcome variables, respectively. Age, gender, education, wealth index, family history, and body mass index (BMI) were included as covariates. We used multiple imputation to account for missing variables. Results Prevalence of hypertension was 30.1%. The mean (SD) sleep duration was 7.3 (1.2) hours. Insomnia, snoring, and EDS were present in 13.6%, 28.7%, and 4.6%, respectively. Moderate and habitual snoring were associated with increased odds of hypertension (odds ratio [OR] = 1.18, 95% confidence interval [CI] [1.04 to 1.33] and 1.47 [1.29 to 1.67], respectively), after adjusting for covariates. Rare, occasional, and frequent insomnia were associated with increased hypertension (OR 1.41 [1.12 to 1.77], 1.39 [1.16 to 1.67], and 1.34 [1.09 to 1.65], respectively). Sleep duration and EDS were not associated with hypertension. Conclusion Self-reported snoring and insomnia were associated with hypertension in South Asia. This relationship needs further exploration through robust longitudinal studies in this region.

Detecting the Cognitive Prodrome of Dementia with Lewy Bodies: A Prospective Study of REM Sleep Behavior Disorder.

Abstract: Study Objectives Long-term studies in REM sleep behavior disorder (RBD) have shown a high rate of conversion into synucleinopathies. We aimed to prospectively follow-up a large cohort of RBD patients to identify cognitive markers for early detection of prodromal dementia. Methods Seventy-six idiopathic RBD patients underwent polysomnography and a complete neuropsychological and neurological assessment and were then followed for a mean of 3.6 years. Cognitive characteristics at baseline were compared between patients who remained disease-free and those who developed a synucleinopathy, and between those who developed dementia first and those who developed parkinsonism first. Receiver operating characteristic curves were calculated to assess the diagnostic value of cognitive tests for detecting prodromal dementia. Results At follow-up, 34 patients developed a neurodegenerative disease: 19 parkinsonism-first and 15 dementia-first. RBD patients who first developed dementia were impaired at baseline in all cognitive domains (attention/executive functions, learning/memory, and visuospatial) compared to patients who developed parkinsonism. Moreover, 93% of patients who first developed dementia had mild cognitive impairment at baseline compared to 42% of patients who developed parkinsonism. RBD patients who developed parkinsonism first were similar at baseline to disease-free RBD patients on cognition. In dementia-first patients, two cognitive tests assessing attention and executive functions (Stroop Color Word Test and Trail Making Test) reliably predicted dementia (area under the curve ≥0.85) compared to parkinsonism-first patients or controls. Conclusions This study shows that cognitive tests assessing attention and executive functions strongly predict conversion to dementia in RBD patients, and may be useful endpoints to determine the effectiveness of interventions to prevent cognitive deterioration in RBD patients.

Asleep at the Wheel—The Road to Addressing Drowsy Driving

Abstract: Drowsy driving is a dangerous behavior that leads to thousands of deaths and injuries each year. It is also a controllable factor for drivers. Drivers are capable of modifying this behavior if given sufficient information and motivation. Our goal is to establish a comprehensive and strategic effort to end drowsy driving crashes and deaths. This article highlights some of the conclusions of a unique recent meeting of sleep experts and highway safety professionals and describes the first steps the community has taken and plans to take in the future to address this issue.