Search

Ya-Ting Yang,1,2 Han-Yun Chang,1 Chung-Yao Hsu,3 Jamie M Zeitzer2,4 1Institute of Education, National Cheng Kung University, Tainan City, Taiwan; 2Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; 3Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Mental Illness Research Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, USACorrespondence: Jamie M Zeitzer Email jzeitzer@stanford.eduPurpose: The Cleveland Adolescent Sleepiness Questionnaire was originally developed and published in English and has served as a valid and effective tool for the assessment of adolescents’ experiences with sleepiness in a variety of situations. To allow for comparisons between sleepiness in adolescents from different cultures, and with different linguistic backgrounds, reliable and valid measurement tools are necessary. The purpose of this study was to translate and validate a Chinese version of the Cleveland Adolescent Sleepiness Questionnaire (C-CASQ).Materials and Methods: Sensitivity, specificity, internal consistency, and criterion validity data for the C-CASQ were tested using 458 adolescents in Taiwan. Data from 191 participants were used to establish internal consistency reliability and conduct exploratory factor analysis (EFA), while data from 267 participants were used to establish criterion validity and conduct confirmatory factor analysis (CFA). Initial criterion validity was established through a comparison of the C-CASQ with scores from the Chinese version of the Morningness-Eveningness Scale for Children, a measure of chronotype.Results: EFA resulted in four factors, consistent with the original English version of the CASQ, while CFA established goodness of fit. The scale demonstrated acceptable to good internal consistency (α = 0.77∼ 0.86). Initial criterion validity was evident as the total score and each of the subscale scores on the C-CASQ was significantly higher (greater sleepiness) in evening-types.Conclusion: The C-CASQ appears to be a psychometrically sound measure to evaluate sleepiness in Chinese-speaking adolescents.Keywords: teens, sleep, alertness, chronotype

Jerome A Yesavage,1,2 Lisa M Kinoshita,1,2 Art Noda,2 Laura C Lazzeroni,2 Jennifer Kaci Fairchild,1,2 Leah Friedman,1,2 Gundeep Sekhon,1,2 Stephanie Thompson,1,2 Jauhtai Cheng,1,2 Jamie M Zeitzer1,2 1Department of Veterans Affairs Health Care System, Palo Alto, CA, USA; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA Purpose: Previous work has demonstrated the relatively high prevalence of risk factors for cognitive impairment, such as sleep disordered breathing (SDB) and obesity, in Vietnam War era veterans with post-traumatic stress disorder (PTSD). No data are currently available on the longitudinal stability of SDB as a risk factor for cognitive decline in that population, which this study now reports. Methods: Sample consisted of 48 veterans of the Vietnam War with PTSD who completed longitudinal sleep assessments over a 3-year period. The primary outcome measure, the Apnea-Hypopnea Index (AHI) indicator, was determined during standard overnight polysomnography. Body mass index (BMI) was calculated using standard measurements. Measures of cognitive function tapped auditory verbal memory as measured by the Rey Auditory Verbal Learning Test and executive functioning as measured by the Color-Word Interference Test of the Delis–Kaplan Executive Function System battery. Statistical analyses included mixed effects modeling. Results: In this sample, AHI increased significantly by 2.19 points per year (β=2.19; P

Jerome A Yesavage,1,2 Lisa M Kinoshita,1,2 Art Noda,2 Laura C Lazzeroni,2 Jennifer Kaci Fairchild,1,2 Joy Taylor,1,2 Doina Kulick,3 Leah Friedman,1,2 Jauhtai Cheng,1,2 Jamie M Zeitzer,1,2 Ruth O’Hara1,21Department of Veterans Affairs Health Care System, Palo Alto, CA, USA; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; 3Department of Medicine, University of Nevada School of Medicine, Reno, NV, USABackground: Well-known risk factors for cognitive impairment are also associated with obesity. Research has highlighted genetic risk factors for obesity, yet the relationship of those risk factors with cognitive impairment is unknown. The objective of this study was to determine the associations between cognition, hypertension, diabetes, sleep-disordered breathing, and obesity. Genetic risk factors of obesity were also examined.Methods: The sample consisted of 369 nondemented individuals aged 50 years or older from four community cohorts. Primary outcome measures included auditory verbal memory, as measured by the Rey Auditory Verbal Learning Test, and executive functioning, as measured by the Color–Word Interference Test of the Delis–Kaplan Executive Function System battery. Apnea–hypopnea index indicators were determined during standard overnight polysomnography. Statistical analyses included Pearson correlations and linear regressions.Results: Poor executive function and auditory verbal memory were linked to cardiovascular risk factors, but not directly to obesity. Genetic factors appeared to have a small but measureable association to obesity.Conclusion: A direct linkage between obesity and poor executive function and auditory verbal memory is difficult to discern, possibly because nonobese individuals may show cognitive impairment due to insulin resistance and the “metabolic syndrome”.Keywords: sleep-disordered breathing, hypertension, diabetes, sleep apnea, BMI, obesity

This paper discusses the rise of human-centric lighting and its current status in lighting. We summarise the human benefits associated with light and lighting and show that human-centric lighting has sound motivations, despite being tainted by misleading marketing claims. The phrase integrative lighting avoids the hype and encapsulates what lighting aspires to be. Embodied in these concepts are some things old and some things new. The old is twofold. First, without diminishing the value of lighting products, the core ingredient for good human outcomes is good design, driven by a design team. Second, light is still for vision, and lighting for visibility, visual comfort and visual amenity is as important as ever. Complementing the old is new awareness and responsibility for how light and lighting influence non-visual responses in humans. Circadian, neuroendocrine and neurobehavioural responses are important for human health and should be considered on-par with visual responses. This awareness leads toward lighting design solutions with increased contrast between day and night. The parties responsible for addressing non-visual responses to light and lighting are evolving. Architects, lighting professionals, lighting equipment manufacturers, medical professionals, building owners and individuals all have a stake, but who should drive decisions and in what proportion? [ABSTRACT FROM AUTHOR]

We tested the hypothesis that single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) are associated with apathy in individuals with Alzheimer's disease (AD). We analyzed a cohort of 105 Caucasian individuals with AD (age = 79.3 ± 7.03 years; MMSE = 20.2 ± 4.4) according to the presence of apathy, as defined either by the Neuropsychiatric Inventory or the Apathy Inventory. Polymorphisms in seventeen SNPs in COMT were examined. A replication cohort consisting of 176 Caucasian AD subjects in the ADNI database was also analyzed. None of the candidate gene SNPs were significantly associated with the presence of apathy in either cohort. We did not find any SNPs in COMT that were consistently associated with apathy in individuals with AD. [ABSTRACT FROM AUTHOR]

Aims: Sleep timing, influenced by chronotype, behavior, and circadian rhythms, is critical for human health. While previous research has linked chronotype to various health outcomes, the impact of aligning sleep timing with chronotype on physical health remains underexplored. The objective of this study is to investigate the association between chronotype, actual sleep timing, and their alignment with a spectrum of physical health outcomes., Methods: Objective sleep timing (actigraphy, categorized as early, intermediate, or late) and chronotype (self-reported, categorized as morning, intermediate, or evening types) were derived from the UK Biobank (n=73,888 middle-aged and older adults) and used in cross-sectional and longitudinal analyses. Physical health outcomes included metabolic disorders, diabetes, obesity, hypertension, circulatory disorders, digestive disorders, respiratory disorders, and all-cause cancer based on ICD10 codes. Analyses were adjusted for demographic factors, sleep duration and sleep timing stability., Results: As compared to morning types with early behavior (aligned), morning types with late behavior (misaligned) had an increased risk of all included physical health disorders (p's<0.001). As compared to evening-types with late behavior (aligned), however, evening-types with early behavior (misaligned) had a decreased risk of diabetes, obesity, hypertension, circulatory disorders, and respiratory disorders (p < 0.01). Longitudinal analyses, in which the likelihood of developing de novo physical health disorders was associated with chronotype, behavioral timing, and alignment between the two, confirmed cross-sectional findings., Conclusion: Late sleep timing across chronotypes was consistently associated with adverse physical health outcomes. These findings underscore the importance of going to sleep early, regardless of preference., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024. Published by Elsevier B.V.)

The duration of sleep data collection from actigraphy is often influenced by practical factors (e.g. workdays versus non-workdays), but the impact of the variation of duration on outcome measures of interest has not been well explored. This study investigates the effect of the duration of actigraphy measurement on non-parametric measures of 24-hr sleep-wake rhythms. We examined regularity inter-daily stability and fragmentation intra-daily variation over 14 days or the first 7 days in participants (n = 41) undergoing evaluation for sleep disorders. Bland-Altman plots assessed the impact of fewer than 14 or 7 days, respectively, on inter-daily stability and intra-daily variation scores. Intra-daily variation values were also calculated for each day and compared with the 14-day intra-daily variation. Compared with the entire 14-day period, using shorter durations (< 7 days) led to a higher estimated bias and increased variance in the limits of agreement for inter-daily stability. Intra-daily variation values showed increased variation in the limits of agreement with fewer days. Similar trends were observed when comparing shorter actigraphy periods 3 or 5 days-7 days. Daily intra-daily variation calculations indicate that individuals with higher daily fragmentation experienced more pronounced day-to-day fragmentation and greater variability in the degree of fragmentation, in a linear association between daily intra-daily variation standard deviation and 14-day intra-daily variation values. Our data indicate that a minimum of 7 full days of actigraphy is recommended to reduce measurement errors, and intra-daily variation and inter-daily stability derived from less than 7 days cannot be compared with those from more than 7 days without significant error., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Sleep is impaired in children with attention-deficit/hyperactivity disorder (ADHD). However, population-based examination of indicators of sleep insufficiency and bedtime irregularity is limited. This investigation examined associations between ADHD, weeknight sleep insufficiency, and bedtime irregularity in a nationally-representative child sample, and indicators of these sleep outcomes in ADHD., Methods: Parents of children aged 3-17 years with ADHD (n = 7671) were surveyed through the 2020-2021 National Survey of Children's Health. Inverse probability of treatment weighting generated a weighted matched control sample (n = 51,572). Weighted generalized linear models were performed without and with age-stratification to examine associations between ADHD and sleep, adjusting for sociodemographics in the full sample, and between nineteen sociodemographic and clinical variables and sleep in ADHD., Results: Having ADHD was associated with increased odds of sleep insufficiency and bedtime irregularity relative to controls, even after adjusting for sociodemographic variables. In ADHD, older age was associated with lower sleep insufficiency and greater bedtime irregularity. Black race, increased poverty, higher ADHD severity, depression, and increased screen time were associated with greater sleep insufficiency and bedtime irregularity. Adverse childhood experiences (ACEs) were associated with greater sleep insufficiency. Behavioral/conduct problems, female sex, and absence of both ADHD medication use and ASD diagnosis were associated with poorer bedtime irregularity. Age-stratified results are reported in text., Conclusions: Children with ADHD face heightened risk for insufficient sleep and irregular bedtimes. Findings suggest intervention targets (e.g., Black race, poverty, depression, screen time) to improve both sleep insufficiency and bedtime irregularity. Results highlight ACEs and behavioral/conduct problems as targets to improve sleep insufficiency and bedtime regularity, respectively. Age-stratified findings are discussed., Competing Interests: Declaration of competing interest EJR reports financial support was provided in part by the National Institute of Mental HealthK23MH113884. SKL reports financial support was provided in part by the National Institute of Mental HealthR01MH126041. EJR reports grants from the American Academy of Sleep Medicine, Brain and Behavior Research Foundation, and National Institute of Mental Health, relevant to the submitted work. She also reports speaking and lecture fees from Wink Sleep. SKL reports a grant from the National Institute of Mental Health relevant to the submitted work. TYL, SB, VSS, DSJ, KAK, and JMZ declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Disturbed sleep is frequently identified in adult patients with cancer and their caregivers, with detrimental impact on physical health. Less known is the extent to which self-reported and actigraph-measured sleep patterns are similar between patients and their sleep-partner caregivers, and how these different modes of sleep measurements are related to physical health., Methods: Patients diagnosed with colorectal cancer and their sleep-partner caregivers (81 dyads) completed a questionnaire for physical functioning and collected saliva samples for seven consecutive days, from which cortisol slope was quantified. Additionally, participants completed a daily sleep diary and wore actigraph for 14 consecutive days, from which sleep duration, sleep onset latency (SOL), and duration of wake after sleep onset (WASO) were calculated., Results: Participants reported sleep patterns that fell within or close to the optimal range, which were similar between patients and their caregivers. Self-reported and actigraph-measured sleep duration had moderate levels of agreement (ICC = 0.604), whereas SOL and WASO had poor agreement (ICC = 0.269). Among patients, longer self-reported WASO was associated with poorer physical health and flatter cortisol slope (p ≤ 0.013). Among caregivers, longer self-reported SOL was associated with poorer physical functioning, actigraph-measured WASO was associated with steeper cortisol slope, and longer self-reported sleep markers studied than actigraph-measured were associated with poorer physical functioning (p ≤ 0.042)., Conclusion: Findings suggest that employing multiple assessment modes for sleep and physical health is vital for comprehensive understanding of sleep health. Furthermore, when addressing patients' sleep health, it may be beneficial to include their sleep-partner caregivers who may experience similar disturbed sleep., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Objective: To achieve consensus on whether screen-based digital media (1) in general, (2) via prebedtime content, and (3) via prebedtime light impairs sleep health in (a) childhood, (b) adolescence, and (c) adulthood. Furthermore, to address whether employing behavioral strategies and interventions may reduce the potential negative effects of screens on sleep health., Methods: The National Sleep Foundation convened a 16-person multidisciplinary expert panel ("Panel"). Panelists met virtually 5 times throughout 2023, during which they followed a modified Delphi RAND/UCLA Appropriateness Method to reach consensus., Results: The Panel conducted a literature review starting with 2209 articles, narrowed down to 522 relevant empirical articles and 52 relevant review articles. The search was refined to include 35 experimental/intervention studies that examined whether there was a causal link between screen-based digital media and sleep. In addition, panelists reviewed 5 recent relevant systematic review articles. After reviewing the summarized current literature, panelists voted on 10 candidate statements about whether screen use impairs sleep health. The Panel met virtually to discuss the results of the first round of votes, which was then followed by a second round of voting, ultimately achieving consensus on 5 out of the 10 statements., Conclusions: The Panel achieved consensus that (1) in general, screen use impairs sleep health among children and adolescents, (2) the content of screen use before sleep impairs sleep health of children and adolescents, and (3) behavioral strategies and interventions may attenuate the negative effects of screen use on sleep health., Competing Interests: Declaration of conflicts of interest The authors have declared no conflicts of interest., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Obstructive sleep apnea (OSA) is a common, underdiagnosed sleep-related breathing disorder with serious health implications Objective - We propose a deep transfer learning approach for sleep stage classification and sleep apnea (SA) detection using wrist-worn consumer sleep technologies (CST). Methods - Our model is based on a deep convolutional neural network (DNN) utilizing accelerometers and photo-plethysmography signals from nocturnal recordings. The DNN was trained and tested on internal datasets that include raw data from clinical and wrist-worn devices; external validation was performed on a hold-out test dataset containing raw data from a wrist-worn CST. Results - Training on clinical data improves performance significantly, and feature enrichment through a sleep stage stream gives only minor improvements. Raw data input outperforms feature-based input in CST datasets. The system generalizes well but performs slightly worse on wearable device data compared to clinical data. However, it excels in detecting events during REM sleep and is associated with arousal and oxygen desaturation. We found; cases that were significantly underestimated were characterized by fewer of such event associations. Conclusion - This study showcases the potential of using CSTs as alternate screening solution for undiagnosed cases of OSA. Significance - This work is significant for its development of a deep transfer learning approach using wrist-worn consumer sleep technologies, offering comprehensive validation for data utilization, and learning techniques, ultimately improving sleep apnea detection across diverse devices.

Mental health is independently influenced by the inclination to sleep at specific times (chronotype) and the actual sleep timing (behavior). Chronotype and timing of actual sleep are, however, often misaligned. This study aims to determine how chronotype, sleep timing, and the alignment between the two impact mental health. In a community-dwelling cohort of middle- and older-aged adults (UK Biobank, n = 73,888), we examined the impact of chronotype (questionnaire-based), the timing of behavior (determined with 7-day accelerometry), and the alignment between the two on mental, behavioral, neurodevelopmental disorders (MBN), depression, and anxiety, as assessed through ICD-10 codes. As compared to morning types with early behavior (aligned), morning types with late behavior (misaligned) had an increased risk of having MBN, depression, and anxiety (p's<0.001). As compared to evening-types with late behavior (aligned), however, evening-types with early behavior (misaligned) had a decreased risk of depression (p < 0.01), with a trend for MBN (p = 0.04) and anxiety (p = 0.05). Longitudinal analyses, in which the likelihood of developing de novo mental health disorders was associated with chronotype, behavioral timing, and alignment between the two, confirmed cross-sectional findings. To age healthily, individuals should start sleeping before 1AM, despite chronobiological preferences., Competing Interests: Declaration of competing interest None., (Published by Elsevier B.V.)

Objective: Sleepiness and fatigue are common complaints among individuals with sleep disorders. The two concepts are often used interchangeably, causing difficulty with differential diagnosis and treatment decisions. The current study investigated sleep disorder patients to determine which factors best differentiated sleepiness from fatigue., Methods: The study used a subset of participants from a multi-site study (n = 606), using a cross-sectional study design. We selected 60 variables associated with either sleepiness or fatigue, including demographic, mental health, and lifestyle factors, medical history, sleep questionnaires, rest-activity rhythms (actigraphy), polysomnographic (PSG) variables, and sleep diaries. Fatigue was measured with the Fatigue Severity Scale and sleepiness was measured with the Epworth Sleepiness Scale. A Random Forest machine learning approach was utilized for analysis., Results: Participants' average age was 47.5 years (SD 14.0), 54.6% female, and the most common sleep disorder diagnosis was obstructive sleep apnea (67.4%). Sleepiness and fatigue were moderately correlated (r = 0.334). The model for fatigue (explained variance 49.5%) indicated depression was the strongest predictor (relative explained variance 42.7%), followed by insomnia severity (12.3%). The model for sleepiness (explained variance 17.9%), indicated insomnia symptoms was the strongest predictor (relative explained variance 17.6%). A post hoc receiver operating characteristic analysis indicated depression could be used to discriminate fatigue (AUC = 0.856) but not sleepiness (AUC = 0.643)., Conclusions: The moderate correlation between fatigue and sleepiness supports previous literature that the two concepts are overlapping yet distinct. Importantly, depression played a more prominent role in characterizing fatigue than sleepiness, suggesting depression could be used to differentiate the two concepts., Competing Interests: Declaration of competing interest None. The authors have no competing interests to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sleep-wake regulating circuits are affected during prodromal stages in the pathological progression of both Alzheimer's disease (AD) and Parkinson's disease (PD), and this disturbance can be measured passively using wearable devices. Our objective was to determine whether accelerometer-based measures of 24-h activity are associated with subsequent development of AD, PD, and cognitive decline., Methods: This study obtained UK Biobank data from 82,829 individuals with wrist-worn accelerometer data aged 40 to 79 years with a mean (± SD) follow-up of 6.8 (± 0.9) years. Outcomes were accelerometer-derived measures of 24-h activity (derived by cosinor, nonparametric, and functional principal component methods), incident AD and PD diagnosis (obtained through hospitalization or primary care records), and prospective longitudinal cognitive testing., Results: One hundred eighty-seven individuals progressed to AD and 265 to PD. Interdaily stability (a measure of regularity, hazard ratio [HR] per SD increase 1.25, 95% confidence interval [CI] 1.05-1.48), diurnal amplitude (HR 0.79, CI 0.65-0.96), mesor (mean activity; HR 0.77, CI 0.59-0.998), and activity during most active 10 h (HR 0.75, CI 0.61-0.94), were associated with risk of AD. Diurnal amplitude (HR 0.28, CI 0.23-0.34), mesor (HR 0.13, CI 0.10-0.16), activity during least active 5 h (HR 0.24, CI 0.08-0.69), and activity during most active 10 h (HR 0.20, CI 0.16-0.25) were associated with risk of PD. Several measures were additionally predictive of longitudinal cognitive test performance., Conclusions: In this community-based longitudinal study, accelerometer-derived metrics were associated with elevated risk of AD, PD, and accelerated cognitive decline. These findings suggest 24-h rhythm integrity, as measured by affordable, non-invasive wearable devices, may serve as a scalable early marker of neurodegenerative disease., (© 2024. The Author(s).)

Introduction: High variability in response and retention rates for posttraumatic stress disorder (PTSD) treatment highlights the need to identify "personalized" or "precision" medicine factors that can inform optimal intervention selection before an individual commences treatment. In secondary analyses from a non-inferiority randomized controlled trial, behavioral and physiological emotion regulation were examined as non-specific predictors (that identify which individuals are more likely to respond to treatment, regardless of treatment type) and treatment moderators (that identify which treatment works best for whom) of PTSD outcome., Methods: There were 85 US Veterans with clinically significant PTSD symptoms randomized to 6 weeks of either cognitive processing therapy (CPT; n = 44) or a breathing-based yoga practice (Sudarshan kriya yoga; SKY; n = 41). Baseline self-reported emotion regulation (Difficulties in Emotion Regulation Scale) and heart rate variability (HRV) were assessed prior to treatment, and self-reported PTSD symptoms were assessed at baseline, end-of-treatment, 1-month follow-up, and 1-year follow-up., Results: Greater baseline deficit in self-reported emotional awareness (similar to alexithymia) predicted better overall PTSD improvement in both the short- and long-term, following either CPT or SKY. High self-reported levels of emotional response non-acceptance were associated with better PTSD treatment response with CPT than with SKY. However, all significant HRV indices were stronger moderators than all self-reported emotion regulation scales, both in the short- and long-term. Veterans with lower baseline HRV had better PTSD treatment response with SKY, whereas Veterans with higher or average-to-high baseline HRV had better PTSD treatment response with CPT., Conclusions: To our knowledge, this is the first study to examine both self-reported emotion regulation and HRV, within the same study, as both non-specific predictors and moderators of PTSD treatment outcome. Veterans with poorer autonomic regulation prior to treatment had better PTSD outcome with a yoga-based intervention, whereas those with better autonomic regulation did better with a trauma-focused psychological therapy. Findings show potential for the use of HRV in clinical practice to personalize PTSD treatment., Clinical Trial Registration: ClinicalTrials.gov identifier, NCT02366403., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mathersul, Zeitzer, Schulz-Heik, Avery and Bayley.)

Objectives: To explore how the blood plasma proteome fluctuates across the 24-hour day and identify a subset of proteins that show endogenous circadian rhythmicity., Methods: Plasma samples from 17 healthy adults were collected hourly under controlled conditions designed to unmask endogenous circadian rhythmicity; in a subset of 8 participants, we also collected samples across a day on a typical sleep-wake schedule. A total of 6916 proteins were analyzed from each sample using the SomaScan aptamer-based multiplexed platform. We used differential rhythmicity analysis based on a cosinor model with mixed effects to identify a subset of proteins that showed circadian rhythmicity in their abundance., Results: One thousand and sixty-three (15%) proteins exhibited significant daily rhythmicity. Of those, 431 (6.2%) proteins displayed consistent endogenous circadian rhythms on both a sleep-wake schedule and under controlled conditions: it included both known and novel proteins. When models were fitted with two harmonics, an additional 259 (3.7%) proteins exhibited significant endogenous circadian rhythmicity, indicating that some rhythmic proteins cannot be solely captured by a simple sinusoidal model. Overall, we found that the largest number of proteins had their peak levels in the late afternoon/evening, with another smaller group peaking in the early morning., Conclusions: This study reveals that hundreds of plasma proteins exhibit endogenous circadian rhythmicity in humans. Future analyses will likely reveal novel physiological pathways regulated by circadian clocks and pave the way for improved diagnosis and treatment for patients with circadian disorders and other pathologies. It will also advance efforts to include knowledge about time-of-day, thereby incorporating circadian medicine into personalized medicine., Competing Interests: Declaration of conflicts of interest Mr. Specht and Mr. Kolosov, and Drs. Arrona-Palacios, Bueno, Cederberg, Duffy, Pardilla-Delgado, Ruiz-Herrera, Zeitzer, and Zitting, declare no conflict of interest. Dr. Pardilla-Delgado is currently employed by Vanda Pharmaceuticals, but this work is unrelated to his position there. Dr. Kramer’s institution has issued patents (PCT/EP2018/066771) related to biomarkers for detecting the clock. This intellectual property has been licensed by BodyClock Technologies GmbH, in which Dr. Kramer is a shareholder. Dr. Mignot occasionally consults and has received contracts from Jazz Pharmaceuticals, Orexia/Centessa, Takeda and ActiGraph; has received grant/clinical trial funding from Harmony, Takeda, Apple, Huami, Sunovion, Idorsia, Eisai; is and has been a Principal Investigator on clinical trials using oxybate salts, orexin agonists and Solriamfetol, Pharmaceutical products, for the treatment of Type 1 narcolepsy; all outside the scope of this work. Dr. Czeisler serves as the incumbent of an endowed professorship provided to Harvard Medical School by Cephalon, Inc., and reports institutional support for a Quality Improvement Initiative from Delta Airlines and Puget Sound Pilots; education support to Harvard Medical School Division of Sleep Medicine and support to Brigham and Women’s Hospital from: Jazz Pharmaceuticals PLC, Inc, Philips Respironics, Inc., Optum, and ResMed, Inc.; research support to Brigham and Women’s Hospital from Axome Therapeutics, Inc., Dayzz Ltd., Peter Brown and Margaret Hamburg, Regeneron Pharmaceuticals, Sanofi SA, Casey Feldman Foundation, Summus, Inc., Takeda Pharmaceutical Co., LTD, Abbaszadeh Foundation, CDC Foundation; educational funding to the Sleep and Health Education Program of the Harvard Medical School Division of Sleep Medicine from ResMed, Inc., Teva Pharmaceuticals Industries, Ltd., and Vanda Pharmaceuticals; personal royalty payments on sales of the Actiwatch-2 and Actiwatch-Spectrum devices from Philips Respironics, Inc; personal consulting fees from Axsome, Inc., Bryte Foundation, With Deep, Inc., and Vanda Pharmaceuticals, the Institute of Digital Media and Child Development, the Klarman Family Foundation, and the UK Biotechnology and Biological Sciences Research Council; honoraria from the Associated Professional Sleep Societies, the Massachusetts Medical Society, the National Council for Mental Wellbeing, and the National Sleep Foundation; lecture fees from Teva Pharma Australia PTY Ltd. and Emory University. Dr. Czeisler has received personal fees for serving as an expert witness on a number of civil matters, criminal matters, and arbitration cases, including those involving the following commercial and government entities: Amtrak; Bombardier, Inc.; C&J Energy Services; Dallas Police Association; Delta Airlines/Comair; Enterprise Rent-A-Car; FedEx; Greyhound Lines, Inc./Motor Coach Industries/FirstGroup America; PAR Electrical Contractors, Inc.; Puget Sound Pilots; and the San Francisco Sheriff’s Department; Schlumberger Technology Corp.; Union Pacific Railroad; United Parcel Service; Vanda Pharmaceuticals. Dr. Czeisler has received travel support from the Stanley Ho Medical Development Foundation, Merck Sharpe and Dohme; equity interest in Vanda Pharmaceuticals, With Deep, Inc, and Signos, Inc.; and institutional educational gifts to Brigham and Women’s Hospital from Johnson & Johnson, Mary Ann and Stanley Snider via Combined Jewish Philanthropies, Alexandra Drane, DR Capital, Harmony Biosciences, LLC, San Francisco Bar Pilots, Whoop, Inc., Harmony Biosciences LLC, Eisai Co., LTD, Idorsia Pharmaceuticals LTD, Sleep Number Corp., Apnimed, Inc., Avadel Pharmaceuticals, Bryte Foundation, f.lux Software, LLC, and the Stuart F. and Diana L. Quan Charitable Fund. Dr Czeisler's interests, which are all outside the scope of this work, were reviewed and are managed by the Brigham and Women's Hospital and Mass General Brigham in accordance with their conflict-of interest policies., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: This study evaluated the effects of early time-restricted eating (eTRE) on shifting the timing of sleep among late sleepers. Primary outcomes included actigraphy- and sleep diary-derived sleep onset, midsleep phase, and wake time with total sleep time as a secondary outcome., Methods: Fifteen healthy adults with habitual late sleep timing were randomized to receive either eTRE or sleep and nutrition hygiene (control) via a single 30-minute synchronous video session. Participants completed an initial 1-week baseline phase followed by a 2-week intervention phase. Measures included continuous sleep monitoring and sleep and nutrition diaries., Results: Linear mixed-effects modeling demonstrated that eTRE significantly advanced sleep timing compared with controls. Self-reported sleep onset (56.1 [95% confidence interval: 20.5, 91.7] minutes), midpoint (19.5 [7.2, 31.9] minutes), and offset (42.2 [2.9, 81.5] minutes) each moved earlier in eTRE as compared with controls. Similarly, objectively determined sleep onset (66.5 [29.6, 103.4] minutes), midpoint (21.9 [9.1, 34.7] minutes), and offset (39.3 [1.3, 77.3] minutes) each moved earlier in eTRE as compared with controls. Total sleep time showed a nonsignificant increase in the eTRE group as compared with controls., Conclusions: Late sleepers who were instructed in a single session about eTRE significantly advanced their sleep timing, especially sleep onset. eTRE shows potential as a clinical strategy for advancing sleep timing in late sleepers., Clinical Trial Registration: Registry: Chinese Clinical Trial Registry; Name: FAST Asleep: It's All About Timing; URL: https://www.chictr.org.cn/showproj.html?proj=122504; Identifier: ChiCTR2100043691., Citation: Blum DJ, Hernandez B, Zeitzer JM. Early time-restricted eating advances sleep in late sleepers: a pilot randomized controlled trial. J Clin Sleep Med . 2023;19(12):2097-2106., (© 2023 American Academy of Sleep Medicine.)

Little is known about links of circadian rhythm alterations with neuropsychiatric symptoms and cognition in memory impaired older adults. Associations of actigraphic rest/activity rhythms (RAR) with depressive symptoms and cognition are examined using function-on-scalar regression (FOSR). Forty-four older adults with memory impairment (mean: 76.84 ± 8.15 years; 40.9% female) completed 6.37 ± 0.93 days of actigraphy, the Beck depression inventory-II (BDI-II), mini-mental state examination (MMSE) and consortium to establish a registry for Alzheimer's disease (CERAD) delayed word recall. FOSR models with BDI-II, MMSE, or CERAD as individual predictors adjusted for demographics (Models A1-A3) and all three predictors and demographics (Model B). In Model B, higher BDI-II scores are associated with greater activity from 12:00-11:50 a.m., 2:10-5:50 p.m., 8:40-9:40 p.m., 11:20-12:00 a.m., higher CERAD scores with greater activity from 9:20-10:00 p.m., and higher MMSE scores with greater activity from 5:50-10:50 a.m. and 12:40-5:00 p.m. Greater depressive symptomatology is associated with greater activity in midafternoon, evening, and overnight into midday; better delayed recall with greater late evening activity; and higher global cognitive performance with greater morning and afternoon activity (Model B). Time-of-day specific RAR alterations may affect mood and cognitive performance in this population., (© 2023 Wiley-VCH GmbH.)

Background: Older men with the worse alignment of activity and light may have lower levels of cognition and increased rates of cognitive decline., Methods: This cohort consisted of 1 036 older men (81.1 ± 4.6 years) from the MrOS Sleep Study (2009-2012). Light and activity levels were gathered by wrist actigraphy. Phasor analysis was used to quantify the alignment of light-dark and rest-activity patterns (magnitude) and their temporal relationship (angle). Global cognitive function (Modified Mini-Mental State examination [3MS]) and executive function (Trails B test) were measured, then repeated 4.2 ± 0.8 years later. Linear regression models examined the associations of phasor magnitude and angle with cognition and cognitive decline. Models were adjusted for age, clinic, race, education, and season., Results: Smaller phasor magnitude (worse aligned light and activity patterns) was associated with lower initial level and increased decline in executive function. Compared to those with higher phasor magnitude, those with lower magnitude took an average of 11.1 seconds longer to complete the Trails B test (quartile 1 vs quartile 4, p = .02). After follow-up, Trails B completion time increased an average of 5.5 seconds per standard deviation decrease in phasor magnitude (95% confidence interval [CI] 0.7-10.4, p = .03). There were no associations with phasor angle, and none with magnitude and global cognition (3MS)., Conclusion: Among older men, worse alignment of light and activity patterns was associated with worse initial performance and increased decline in executive function, but not related to global cognition. Interventions that improve the alignment of light and activity may slow cognitive decline in older adults., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In humans, exposure to continuous light is typically used to change the timing of the circadian clock. This study examines the efficiency of a sequence of light flashes ("flash therapy") applied during sleep to shift the clock. Healthy participants (n = 10) took part in two 36-h laboratory stays, receiving a placebo (goggles, no light) during one visit and the intervention (goggles, 2-ms flashes broad-spectrum light for 60 min, delivered every 15 s, starting 30 min after habitual sleep onset) during the other. Circadian phase shift was assessed with changes in salivary dim light melatonin onset (DLMO). Sleep, measured with polysomnography, was analyzed to assess changes in sleep architecture and spectral power. After 1 h of flashes, DLMO showed a substantial delay (1.13 ± 1.27 h) compared to placebo (12 ± 20 min). Two individuals exhibited very large shifts of 6.4 and 3.1 h. There were no substantive differences in sleep architecture, but some evidence for greater instability in sleep. 1 h of flash therapy during sleep evokes large changes in circadian timing, up to 6 h, and does so with only minimal, if any, impact on sleep. Flash therapy may offer a practical option to delay the circadian clock in shift workers and jet travelers., (© 2023. Springer Nature Limited.)

Purpose: Circadian rest-Activity Rhythm Disorders (CARDs) are common in patients with cancer, particularly in advanced disease. CARDs are associated with increased symptom burden, poorer quality of life, and shorter survival. Research and reporting practices lack standardization, and formal diagnostic criteria do not exist. This electronic Delphi (e-Delphi) study aimed to formulate international recommendations for the assessment and diagnosis of CARDs in patients with cancer., Methods: An international e-Delphi was performed using an online platform (Welphi). Round 1 developed statements regarding circadian rest-activity rhythms, diagnostic criteria, and assessment techniques. Rounds 2 and 3 involved participants rating their level of agreement with the statements and providing comments until consensus (defined internally as 67%) and stability between rounds were achieved. Recommendations were then created and distributed to participants for comments before being finalized., Results: Sixteen participants from nine different clinical specialties and seven different countries, with 5-35 years of relevant research experience, were recruited, and thirteen participants completed all three rounds. Of the 164 generated statements, 66% achieved consensus, and responses were stable between the final two rounds., Conclusions: The e-Delphi resulted in international recommendations for assessing and diagnosing CARDs in patients with cancer. These recommendations should ensure standardized research and reporting practices in future studies.

Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is caused by motor disinhibition during REM sleep and is a strong early predictor of Parkinson's disease. However, screening questionnaires for iRBD lack specificity due to other sleep disorders that mimic the symptoms. Nocturnal wrist actigraphy has shown promise in detecting iRBD by measuring sleep-related motor activity, but it relies on sleep diary-defined sleep periods, which are not always available. Our aim was to precisely detect iRBD using actigraphy alone by combining two actigraphy-based markers of iRBD - abnormal nighttime activity and 24-hour rhythm disruption. In a sample of 42 iRBD patients and 42 controls (21 clinical controls with other sleep disorders and 21 community controls) from the Stanford Sleep Clinic, the nighttime actigraphy model was optimized using automated detection of sleep periods. Using a subset of 38 iRBD patients with daytime data and 110 age-, sex-, and body-mass-index-matched controls from the UK Biobank, the 24-hour rhythm actigraphy model was optimized. Both nighttime and 24-hour rhythm features were found to distinguish iRBD from controls. To improve the accuracy of iRBD detection, we fused the nighttime and 24-hour rhythm disruption classifiers using logistic regression, which achieved a sensitivity of 78.9%, a specificity of 96.4%, and an AUC of 0.954. This study preliminarily validates a fully automated method for detecting iRBD using actigraphy in a general population.Clinical relevance- Actigraphy-based iRBD detection has potential for large-scale screening of iRBD in the general population.

Controlled breathwork practices have emerged as potential tools for stress management and well-being. Here, we report a remote, randomized, controlled study (NCT05304000) of three different daily 5-min breathwork exercises compared with an equivalent period of mindfulness meditation over 1 month. The breathing conditions are (1) cyclic sighing, which emphasizes prolonged exhalations; (2) box breathing, which is equal duration of inhalations, breath retentions, and exhalations; and (3) cyclic hyperventilation with retention, with longer inhalations and shorter exhalations. The primary endpoints are improvement in mood and anxiety as well as reduced physiological arousal (respiratory rate, heart rate, and heart rate variability). Using a mixed-effects model, we show that breathwork, especially the exhale-focused cyclic sighing, produces greater improvement in mood (p < 0.05) and reduction in respiratory rate (p < 0.05) compared with mindfulness meditation. Daily 5-min cyclic sighing has promise as an effective stress management exercise., Competing Interests: Declaration of interests A.D.H. became an advisor to WHOOP in June of 2022., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Wrist-worn consumer sleep technologies (CST) that contain accelerometers (ACC) and photoplethysmography (PPG) are increasingly common and hold great potential to function as out-of-clinic (OOC) sleep monitoring systems. However, very few validation studies exist because raw data from CSTs are rarely made accessible for external use. We present a deep neural network (DNN) with a strong temporal core, inspired by U-Net, that can process multivariate time series inputs with different dimensionality to predict sleep stages (wake, light-, deep-, and REM sleep) using ACC and PPG signals from nocturnal recordings. The DNN was trained and tested on 3 internal datasets, comprising raw data both from clinical and wrist-worn devices from 301 recordings (PSG-PPG: 266, Wrist-worn PPG: 35). External validation was performed on a hold-out test dataset containing 35 recordings comprising only raw data from a wrist-worn CST. An accuracy = 0.71 ± 0.09, 0.76 ± 0.07, 0.73 ± 0.06, and κ = 0.58 ± 0.13, 0.64 ± 0.09, 0.59 ± 0.09 was achieved on the internal test sets. Our experiments show that spectral preprocessing yields superior performance when compared to surrogate-, feature-, raw data-based preparation. Combining both modalities produce the overall best performance, although PPG proved to be the most impactful and was the only modality capable of detecting REM sleep well. Including ACC improved model precision to wake and sleep metric estimation. Increasing input segment size improved performance consistently; the best performance was achieved using 1024 epochs (∼8.5 hrs.). An accuracy = 0.69 ± 0.13 and κ = 0.58 ± 0.18 was achieved on the hold-out test dataset, proving the generalizability and robustness of our approach to raw data collected with a wrist-worn CST.

Unlike light input for forming images, non-image-forming retinal pathways are optimized to convey information about the total light environment, integrating this information over time and space. In a variety of species, discontinuous light sequences (flashes) can be effective stimuli, notably impacting circadian entrainment. In this study, we examined the extent to which this temporal integration can occur. A group of healthy, young ( n = 20) individuals took part in a series of 16-day protocols in which we examined the impact of different lengths of light flash sequences on circadian timing. We find a significant phase change of -0.70 h in response to flashes that did not differ by duration; a 15-min sequence could engender as much change in circadian timing as 3.5-h sequences. Acute suppression of melatonin was also observed during short (15-min) exposures, but not in exposures over one hour in length. Our data are consistent with the theory that responses to light flashes are mediated by the extrinsic, rod/cone pathway, and saturate the response of this pathway within 15 min. Further excitation leads to no greater change in circadian timing and an inability to acutely suppress melatonin, indicating that this pathway may be in a refractory state following this brief light stimulation.

Objective: Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial., Setting: Outpatient Veterans Affairs healthcare centre., Participants: 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study., Interventions: SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks., Measures: The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS)., Results: Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6 weeks (end of treatment) relative to baseline (SKY, -5.6, d= 0.41, n=41: CPT, -6.8, d= 0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (-1.2, 95% CI -5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT-SKY: -2.1, 95% CI -6.9 to 2.8) and 1-year (CPT-SKY: -1.8, 95% CI -6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1 month, but SKY was inferior to CPT on both BDI-II and PANAS at 1 year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95% CI 0.51 to 3.62, p=0.54)., Conclusions: SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD., Trial Registration Number: NCT02366403., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Light at night can improve alertness and cognition. Exposure to daytime light, however, has yielded less conclusive results. In addition to direct effects, daytime light may also mitigate the impact of nocturnal light exposure on alertness. To examine the impact of daytime lighting on daytime cognitive performance, and evening alertness, we studied nine healthy individuals using a within subject crossover design. On four visits, participants were exposed to one of four lighting conditions for 10 h (dim fluorescent, room fluorescent, broad-spectrum LED, standard white LED; the latter three conditions were matched for 100 lx) followed by an exposure to bright evening light. Cognitive performance, subjective and objective measures of alertness were regularly obtained. While daytime alertness was not impacted by light exposure, the broad-spectrum LED light improved several aspects of daytime cognition. The impact of evening light on alertness was not mitigated by the pre-exposure to different daytime lighting conditions. Results suggest that daytime exposure to white light with high melanopic efficacy has the potential to improve daytime cognitive function and that such improvements are likely to be direct rather than a consequence of light-induced changes in alertness., (Published by Elsevier B.V.)

Background: Emotion regulation (ER) is a key process underlying posttraumatic stress disorder (PTSD), yet, little is known about how ER changes with PTSD treatment. Understanding these effects may shed light on treatment processes., Methods: We recently completed a non-inferiority design randomised controlled trial demonstrating that a breathing-based yoga practice (Sudarshan kriya yoga; SKY) was not clinically inferior to cognitive processing therapy (CPT) across symptoms of PTSD, depression, or negative affect. Here, in secondary exploratory analyses (intent-to-treat N = 85; per protocol N = 59), we examined whether self-reported ER (Difficulties in Emotion Regulation Scale; DERS) and physiological ER (heart rate variability; HRV) improved with treatment for clinically significant PTSD symptoms among US Veterans., Results: DERS-Total and all six subscales improved with small-to-moderate effect sizes (d = .24-.66) following CPT or SKY, with no differences between treatment groups. Following SKY (but not CPT), HR max-min (average difference between maximum and minimum beats per minute), LF/HF (low-to-high frequency) ratio, and normalised HF-HRV (high frequency power) improved (moved towards a healthier profile; d = .42-.55)., Conclusions: To our knowledge, this is the first study to demonstrate that a breathing-based yoga (SKY) improved both voluntary/intentional and automatic/physiological ER. In contrast, trauma-focused therapy (CPT) only reliably improved self-reported ER. Findings have implications for PTSD treatment and interventions for emotional disorders more broadly., Trial Registration: Secondary analyses of ClinicalTrials.gov NCT02366403 ., (© 2022. The Author(s).)

Study Objectives: The measurable aspects of brain function (polysomnography, PSG) that are correlated with sleep satisfaction are poorly understood. Using recent developments in automated sleep scoring, which remove the within- and between-rater error associated with human scoring, we examine whether PSG measures are associated with sleep satisfaction., Design and Setting: A single night of PSG data was compared to contemporaneously collected measures of sleep satisfaction with Random Forest regressions. Whole and partial night PSG data were scored using a novel machine learning algorithm., Participants: Community-dwelling adults (N = 3165) who participated in the Sleep Heart Health Study., Interventions: None., Measurements and Results: Models explained 30% of sleep depth and 27% of sleep restfulness, with a similar top four predictors: minutes of N2 sleep, sleep efficiency, age, and minutes of wake after sleep onset (WASO). With increasing self-reported sleep quality, there was a progressive increase in N2 and decrease in WASO of similar magnitude, without systematic changes in N1, N3 or REM sleep. In comparing those with the best and worst self-reported sleep satisfaction, there was a range of approximately 30 min more N2, 30 min less WASO, an improvement of sleep efficiency of 7-8%, and an age span of 3-5 years. Examination of sleep most proximal to morning awakening revealed no greater explanatory power than the whole-night data set., Conclusions: Higher N2 and concomitant lower wake is associated with improved sleep satisfaction. Interventions that specifically target these may be suitable for improving the self-reported sleep experience., (Published by Elsevier B.V.)

Background: The 24-h rest and activity behaviors (i.e., physical activity, sedentary behaviors and sleep) are fundamental human behaviors essential to health and well-being. Functional principal component analysis (fPCA) is a flexible approach for characterizing rest-activity rhythms and does not rely on a priori assumptions about the activity shape. The objective of our study is to apply fPCA to a nationally representative sample of American adults to characterize variations in the 24-h rest-activity pattern, determine how the pattern differs according to demographic, socioeconomic and work characteristics, and examine its associations with general health status., Methods: The current analysis used data from adults 25 or older in the National Health and Nutrition Examination Survey (NHANES, 2011-2014). Using 7-day 24-h actigraphy recordings, we applied fPCA to derive profiles for overall, weekday and weekend rest-activity patterns. We examined the association between each rest-activity profile in relation to age, gender, race/ethnicity, education, income and working status using multiple linear regression. We also used multiple logistic regression to determine the relationship between each rest-activity profile and the likelihood of reporting poor or fair health., Results: We identified four distinct profiles (i.e., high amplitude, early rise, prolonged activity window, biphasic pattern) that together accounted for 86.8% of total variation in the study sample. We identified numerous associations between each rest-activity profile and multiple sociodemographic characteristics. We also found evidence suggesting the associations differed between weekdays and weekends. Finally, we reported that the rest-activity profiles were associated with self-rated health., Conclusions: Our study provided evidence suggesting that rest-activity patterns in human populations are shaped by multiple demographic, socioeconomic and work factors, and are correlated with health status., (© 2022. The Author(s).)

The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterized by a delayed off-time following the cessation of light stimulation. Here, we exploited this unusual physiologic property to characterize the exquisite sensitivity of the human circadian system to flashed light. In a 34 h in-laboratory between-subjects design, we examined phase shifting in response to variable-intensity (3-9500 photopic lux) flashes at fixed duration (2 ms; n = 28 participants) and variable-duration (10 µs-10 s) flashes at fixed intensity (2000 photopic lux; n = 31 participants). Acute melatonin suppression, objective alertness and subjective sleepiness during the flash sequence were also assessed. We find a dose-response relationship between flash intensity and circadian phase shift, with an indication of a possible threshold-like behaviour. We find a slight parametric relationship between flash duration and circadian phase shift. Consistent with prior studies, we observe no dose-response relationship to either flash intensity or duration and the acute impact of light on melatonin suppression, objective alertness or subjective sleepiness. Our findings are consistent with circadian responses to a sequence of flashes being mediated by rod or cone photoreceptors via ipRGC integration.

The central pacemaker of flies, rodents, and humans generates less robust circadian output signals across normative aging. It is not well understood how changes in light sensitivity might contribute to this phenomenon. In the present study, we summarize results from an extended data series (n = 5681) showing that the locomotor activity rhythm of aged Drosophila can phase-shift normally to intermittently spaced episodes of bright polychromatic light exposure (600 lx) but that deficits emerge in response to 8, 16, and 120-millisecond flashes of narrowband blue (λ m , 452 nm) and green (λ m , 525 nm) LED light. For blue, phase-resetting of the activity rhythm of older flies is not as energy efficient as it is in younger flies at the fastest flash-exposures tested (8 milliseconds), suggesting there might be different floors of light duration necessary to incur photohabituation in each age group. For green, the responses of older flies are universally crippled relative to those of younger flies across the slate of protocols we tested. The difference in green flash photosensitivity is one of the most salient age-related phenotypes that has been documented in the circadian phase-shifting literature thus far. These data provide further impetus for investigations on pacemaker aging and how it might relate to changes in the circadian system's responses to particular sequences of light exposure tuned for wavelength, intensity, duration, and tempo., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Altered 24-hour rest-activity rhythms may be associated with cognitive impairment in older adults, but evidence from prospective studies is limited. Nonparametric methods were used to assess actigraphy-based activity patterns in 2 496 older men. Incident cognitive impairment was assessed 4 times over 12 years using the Modified Mini-Mental State Examination (3MS) and Trails B tests, self-reported medication use, and clinical diagnosis. The highest quartile (vs the lowest) of intradaily variability and the lowest quartiles (vs the highest) of interdaily stability and relative amplitude were associated with incident cognitive impairment (hazard ratio [95% confidence interval]: 1.82 [1.31-2.53], 1.36 [0.99-1.86], and 1.85 [1.33-2.56], respectively). A larger increase in intradaily variability over 7.5 years was associated with a greater subsequent decline in 3MS scores but not in Trails B performance. In conclusion, less stable and more variable rest-activity rhythms may represent early biomarkers of cognitive impairment in older men., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Persons > 65 years with short sleep duration (≤ 6 hours) are at risk for adverse outcomes, but the accuracy of self-reported sleep duration may be affected by reduced symptom awareness. We evaluated the performance characteristics of self-reported vs objectively measured sleep duration in this age group., Methods: In 2,980 men from the Osteoporotic Fractures in Men Sleep Study and 2,855 women from the Study of Osteoporotic Fractures we examined the agreement and accuracy of self-reported vs actigraphy-measured short and normal (> 6 but < 9 hours) sleep duration. We evaluated associations of select factors (demographics; medical, physical, and neuropsychiatric conditions; medication and substance use; and sleep-related measures) with risk of false-negative (normal sleep duration by self-report but short sleep duration by actigraphy) and false-positive (short sleep duration by self-report and normal sleep duration by actigraphy) designations, respectively, using logistic regression., Results: Average ages were 76.3 ± 5.5 and 83.5 ± 3.7 years in men and women, respectively. There was poor agreement between self-reported and actigraphic sleep duration (kappa ≤ 0.24). False negatives occurred in nearly half and false positives in over a quarter of older persons. In multivariable models in men and women, false negatives were independently associated with obesity, daytime sleepiness, and napping, while false positives were significantly lower with obesity., Conclusions: Under- and overreporting of short sleep is common among older persons. Reliance on self-report may lead to missed opportunities to prevent adverse outcomes or unnecessary interventions. Self-reported sleep duration should be objectively confirmed when evaluating the effect of sleep duration on health outcomes., Citation: Miner B, Stone KL, Zeitzer JM, et al. Self-reported and actigraphic short sleep duration in older adults. J Clin Sleep Med . 2022;18(2):403-413., (© 2022 American Academy of Sleep Medicine.)

Light is the preeminent external influence in determining the position of the internal circadian clock relative to the outside world. In this chapter, we discuss the different parameters of light that impact how it influences the human circadian clock. We detail how the timing (phase), intensity, duration and temporal structure, and spectral composition all can modulate the impact of light on both the timing of the circadian clock as well as its amplitude. The neurobiological underpinnings of the system are briefly discussed in the context of understanding how light can evoke its observed effects on the circadian clock., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Study Objectives: Disrupted daily rhythms are associated with mild cognitive impairment (MCI) and dementia. The specific nature of how rhythms and cognition are related, however, is unknown. We hypothesized characteristics from a nonparametric estimate of circadian rest-activity rhythm patterns would be associated to the development of MCI or dementia., Methods: Wrist actigraphy from 1232 cognitively healthy, community-dwelling women (mean age 82.6 years) from the Study of Osteoporotic Fractures was used to estimate rest-activity patterns, including intradaily variability (IV), interdaily stability (IS), most active 10-hour period (M10), least active 5-hour period (L5), and relative amplitude (RA). Logistic regression examined associations of these predictors with 5-year incidence of MCI or dementia. Models were adjusted for potential confounders., Results: Women with earlier sleep/wake times had higher risk of dementia, but not MCI, (early vs. average L5 midpoint: OR, 1.66; 95% CI, 1.08-2.55) as did women with smaller day/night activity differentials (low vs. high RA: OR, 1.96; 95% CI, 1.14-3.35). IV, IS, and M10 were not associated with MCI or dementia., Conclusion: The timing and difference in day/night amplitude, but not variability of activity, may be useful as predictors of dementia., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The circadian wake drive is a mathematic representation of the observed increased propensity to stay awake late in the day, peaking in the hours just before anticipated bed time. It has been called the "forbidden zone" due to the difficulty in initiating sleep during this time and is responsible for the problems initiating sleep when traveling eastward, for maintaining daytime sleep in shift workers, and for initiating sleep in some individuals with insomnia. Evidence culled from studies in individuals with narcolepsy, who lack production of hypocretin (orexin) neuropeptides, as well as a primate model of human wake consolidation and pharmacologic studies of hypocretin antagonists indicate that hypocretin-1 may be the physiologic instantiation of the circadian wake drive. This review will discuss the evidence in support of this hypothesis., (Published by Elsevier Inc.)

Aims: Accumulating evidence suggests Gulf War illness (GWI) is characterised by autonomic nervous system dysfunction (higher heart rate [HR], lower heart rate variability [HRV]). Yoga - an ancient mind-body practice combining mindfulness, breathwork, and physical postures - is proposed to improve autonomic dysfunction yet this remains untested in GWI. We aimed to determine (i) whether HR and HRV improve among Veterans with GWI receiving either yoga or cognitive behavioural therapy (CBT) for pain; and (ii) whether baseline autonomic functioning predicts treatment-related pain outcomes across follow-up., Main Methods: We present secondary analyses of 24-hour ambulatory cardiac data (mean HR, square root of the mean squared differences between successive R-R intervals [RMSSD], high frequency power [HF-HFV], and low-to-high frequency ratio [LF/HF] extracted from a 5-min window during the first hour of sleep) from our randomised controlled trial of yoga versus CBT for pain among Veterans with GWI (ClinicalTrials.govNCT02378025; N = 75)., Key Findings: Veterans who received CBT tended towards higher mean HR at end-of-treatment. Better autonomic function (lower mean HR, higher RMSSD/HF-HRV) at baseline predicted greater reductions in pain across follow-up, regardless of treatment group. Better baseline autonomic function (mid-range-to-high RMSSD/HF-HRV) also predicted greater pain reductions with yoga, while worse baseline autonomic function (higher mean HR, lower RMSSD/HF-HRV) predicted greater pain reductions with CBT., Significance: To our knowledge, this is the first study to suggest that among Veterans with GWI, HR may increase with CBT yet remain stable with yoga. Furthermore, HR and HRV moderated pain outcome across follow-up for yoga and CBT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Epworth Sleepiness Scale is commonly used to examine self-reported daytime sleepiness in clinical populations; the physiologic correlates of this scale, however, are not well understood. Furthermore, how well this scale correlates with parallel objective and self-reported concepts of daytime sleepiness is not well described. As such, we used machine learning algorithms to examine the association between Epworth Sleepiness Scale scores and 55 sleep and medical variables in the Sleep Heart Health Study ( N = 2105). Secondary analyses examined data stratified by age and gender and the relationship between the Epworth and other measures of daytime sleepiness. Analyses of the main data set resulted in low explained variance (7.15%-10.0%), with self-reported frequency of not getting enough sleep as most important predictor (10.3%-13.9% of the model variance). Stratification by neither age nor gender significantly improved explained variance. Cross-correlational analysis revealed low correlation of other daytime sleepiness measures to Epworth scores. We find that Epworth scores are not well explained by habitual or polysomnographic sleep values, or other biomedical characteristics. These analyses indicate that there are different, potentially orthogonal dimensions of the concept of "daytime sleepiness" that may be driven by different aspects of sleep physiology. As the physiologic correlates of the Epworth Sleepiness Scale remain to be elucidated, interpretation of the clinical meaning of these scores should be done with caution., (Published by Oxford University Press on behalf of Sleep Research Society 2021.)