Duration invariance and intensity dependence of the human circadian system phase shifting response to brief light flashes.

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.

Rest-activity profiles among U.S. adults in a nationally representative sample: a functional principal component analysis.

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.

Emotion dysregulation and heart rate variability improve in US veterans undergoing treatment for posttraumatic stress disorder: Secondary exploratory analyses from a randomised controlled trial.

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 .

Comparative Effectiveness of Sleep Apnea Screening Instruments During Inpatient Rehabilitation Following Moderate to Severe TBI.

OBJECTIVE: To determine the diagnostic sensitivity and specificity and comparative effectiveness of traditional sleep apnea screening tools in traumatic brain injury (TBI) neurorehabilitation admissions. DESIGN: Prospective diagnostic comparative effectiveness trial of sleep apnea screening tools relative to the criterion standard, attended level 1 polysomnography including encephalography. SETTING: Six TBI Model System Inpatient Rehabilitation Centers. PARTICIPANTS: Between May 2017 and February 2019, 449 of 896 screened were eligible for the trial with 345 consented (77% consented). Additional screening left 263 eligible for and completing polysomnography with final analyses completed on 248. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Area under the curve (AUC) of screening tools relative to total apnea hypopnea index≥15 (AHI, moderate to severe apnea) measured at a median of 47 days post-TBI (interquartile range, 29-47). RESULTS: The Berlin high-risk score (receiving operating curve [ROC] AUC=0.634) was inferior to the Multivariable Apnea Prediction Index (MAPI) (ROC AUC=0.780) (P=.0211; CI, 0.018-0.223) and Snoring, Tired, Observed, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender (STOPBANG) score (ROC AUC=0.785) (P=.001; CI, 0.063-0.230), both of which had comparable AUC (P=.7245; CI, -0.047 to 0.068). Findings were similar for AHI≥30 (severe apnea); however, no differences across scales was observed at AHI≥5. The pattern was similar across TBI severity subgroups except for posttraumatic amnesia (PTA) status wherein the MAPI outperformed the Berlin. Youden's index to determine risk yielded lower sensitivities but higher specificities relative to non-TBI samples. CONCLUSION: This study is the first to provide clinicians with data to support a choice for which sleep apnea screening tools are more effective during inpatient rehabilitation for TBI (STOPBANG, MAPI vs Berlin) to help reduce comorbidity and possibly improve neurologic outcome.

Sleep-wake disorders in Alzheimer's disease: further genetic analyses in relation to objective sleep measures.

This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer's disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.

Optimization of circadian responses with shorter and shorter millisecond flashes.

Recent work suggests that the circadian pacemaker responds optimally to millisecond flashes of light, not continuous light exposure as has been historically believed. It is unclear whether these responses are influenced by the physical characteristics of the pulsing. In the present study, Drosophila (n = 2199) were stimulated with 8, 16 or 120 ms flashes. For each duration, the energy content of the exposure was systematically varied by changing the pulse irradiance and the number of stimuli delivered over a fixed 15 min administration window (64 protocols surveyed in all). Results showed that per microjoule invested, 8 ms flashes were more effective at resetting the circadian activity rhythm than 16- and 120 ms flashes (i.e. left shift of the dose-response curve, as well as a higher estimated maximal response). These data suggest that the circadian pacemaker's photosensitivity declines within milliseconds of light contact. Further introduction of light beyond a floor of (at least) 8 ms leads to diminishing returns on phase-shifting.

Auditory psychomotor vigilance testing in older and young adults: a revised threshold setting procedure.

BACKGROUND: One of the most common ways to examine the daytime impact of sleep loss is the use of the psychomotor vigilance test (PVT). PVT metrics, including median reaction time (RT) and number of lapses, have been examined in a variety of studies in which both acute and chronic sleep times are manipulated. Most of these studies involve young, healthy individuals and use a visual stimulus. As light is a possible countermeasure to sleep loss, and sometimes incompatible with the use of visual PVT, PVT with auditory cues (aPVT) has been used. A threshold of 400 ms is commonly used to delineate lapses from normal RT in the aPVT. As aging can influence a variety of brain functions, we wanted to examine whether this lapse threshold was accurate for use in older adults. METHODS: Twenty-eight young and 19 healthy older participants performed a 10-min auditory PVT approximately 90 min before habitual bedtime. The occurrence of lapses was determined by five objective RT thresholds: (1) 400 ms, (2) 500 ms, (3) 2 × median, (4) mean + 2 × SD, and (5) method 4 without outliers. Results of these methods were compared with a triplicate visual inspection of RT histograms to determine RT outside of the expected log normal distribution. RESULTS: In both groups, methods 1, 4, and 5 performed poorly, while methods 2 and 3 were adequate, though method 3 was statistically superior. CONCLUSION: In both age groups, the use of twice the median as an objective threshold had the best concurrence with visual scoring.

Serotonin transporter polymorphism, depressive symptoms, and emotional impulsivity among advanced breast cancer patients.

PURPOSE: This study tested a theory linking a marker of low serotonergic function to both depression and impulsivity in a sample of advanced breast cancer patients, among whom elevated depressive symptoms and difficulty regulating emotions are commonly reported. METHODS: A total of 95 patients provided blood samples for serotonin transporter polymorphic region of the gene (5-HTTLPR) and completed questionnaires that measured depressive symptoms and emotional impulsivity. RESULTS: Structural equation modeling revealed that the s allele of 5-HTTLPR was related to greater depressive symptoms (ß = .20, p < .042) but only marginally to greater emotional impulsivity (ß = .19, p < .068). Depressive symptoms and emotional impulsivity were positively related (ß = .33, p < .003). Further tests explored possible mediation from genotype to one psychological variable via the other. Results suggest that depressive symptoms, particularly perceived interpersonal rejection, may be a pathway linking genotype to emotional impulsivity. CONCLUSIONS: Findings provide the first evidence that low serotonergic function contributes to both depression and impulsivity within a clinically meaningful sample. Furthermore, the link of s allele of 5-HTTLPR to emotional impulsivity was mediated by depressive symptoms, particularly perceptions of social rejection. Findings have implications for advanced breast cancer patients' treatment decision.

Aberrant nocturnal cortisol and disease progression in women with breast cancer.

While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p < 0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r = -0.30, p = 0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer.

Ubiquity of Undiagnosed Sleep Disordered Breathing in Community-Dwelling Older Male Veterans.

OBJECTIVE: To determine the point prevalence of sleep disordered breathing (SDB) in a community-based sample of older male veterans and to determine if common markers of SDB apply to this population. METHODS: Two hundred fourteen older male Veterans (age 55-89 years) were recruited for a study on post-traumatic stress disorder and cognitive decline. Questionnaires concerning anthropomorphic and psychological variables were obtained, as was an overnight polysomnographic examination of sleep. RESULTS: Only 13% of the participants lacked clinically meaningful SDB, whereas 33% had moderate SDB and 54% had severe SDB. Being overweight, self-reported snoring, and excessive daytime sleepiness all had good sensitivity (0.86-0.92) but very poor specificity (0.10-0.28) for the prediction of SDB. CONCLUSIONS: Undiagnosed SDB was more than threefold higher than expected in these community-dwelling older veterans. Traditional markers of SDB were not specific for predicting clinically relevant SDB.

Correspondence of plasma and salivary cortisol patterns in women with breast cancer.

INTRODUCTION: The 'diurnal slope' of salivary cortisol has been used as a measure of stress and circadian function in a variety of reports with several detailing its association with cancer progression. The relationship of this slope, typically a negative value from high morning concentrations to low evening concentrations, to the underlying daily variation in total plasma cortisol throughout the 24-hour cycle, however, has never been reported. METHODS: To examine the relationship between the diurnal salivary cortisol slope and the underlying pattern of plasma cortisol in individuals with cancer, we examined a cohort of women with advanced breast cancer (n = 97) who had saliva and plasma collected during a modified 24-hour, constant posture protocol. RESULTS: We found that the steepness of the diurnal slope of salivary cortisol was correlated with the amplitude of plasma cortisol rhythm when the slope was calculated from samples taken at wake + 30 min and 9 PM (r = -0.29, p > 0.05). Other variants of salivary slope calculations were not significantly correlated with the amplitude of the plasma cortisol rhythm. Diurnal salivary cortisol slope steepness was not correlated with the time between habitual waking and the computed circadian peak of cortisol, but there was a correlation between diurnal slope steepness and the time between habitual waking and the time of the awakening spike of morning cortisol (r values <-0.23, p values <0.05). CONCLUSION: It therefore appears that in women with advanced breast cancer, diurnal salivary cortisol slope primarily represents aspects of the cortisol awakening response in relation to evening levels more than the circadian rhythm of total plasma cortisol.

Randomized controlled trial of pharmacological replacement of melatonin for sleep disruption in individuals with tetraplegia.

OBJECTIVE: To determine the effectiveness of a melatonin agonist for treating sleep disturbances in individuals with tetraplegia. DESIGN: Placebo-controlled, double-blind, crossover, randomized control trial. SETTING: At home. PARTICIPANTS: Eight individuals with tetraplegia, having an absence of endogenous melatonin production and the presence of a sleep disorder. Interventions Three weeks of 8 mg of ramelteon (melatonin agonist) and 3 weeks of placebo (crossover, randomized order) with 2 weeks of baseline prior to and 2 weeks of washout between active conditions. OUTCOME: Change in objective and subjective sleep. MEASURES: Wrist actigraphy, post-sleep questionnaire, Stanford sleepiness scale, SF-36. RESULTS: We observed no consistent changes in either subjective or objective measures of sleep, including subjective sleep latency (P = 0.55, Friedman test), number of awakenings (P = 0.17, Friedman test), subjective total sleep time (P = 0.45, Friedman test), subjective morning alertness (P = 0.35, Friedman test), objective wake after sleep onset (P = 0.70, Friedman test), or objective sleep efficiency (P = 0.78, Friedman test). There were significant increases in both objective total sleep time (P < 0.05, Friedman test), subjective time in bed (P < 0.05, Friedman test), and subjective sleep quality (P < 0.05, Friedman test), although these occurred in both arms. There were no significant changes in any of the nine SF-36 subscale scores (Friedman test, Ps >Bonferroni adjusted α of 0.005). CONCLUSION: In this pilot study, we were unable to show effectiveness of pharmacological replacement of melatonin for the treatment of self-reported sleep problems in individuals with tetraplegia. Trial Registration ClinicalTrials.gov # NCT00507546.

Perils of the nighttime: Impact of behavioral timing and preference on mental health in 73,888 community-dwelling adults.

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.

Fatigued but not sleepy? An empirical investigation of the differentiation between fatigue and sleepiness in sleep disorder patients in a cross-sectional study.

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.

Emotion regulation and heart rate variability may identify the optimal posttraumatic stress disorder treatment: analyses from a randomized controlled trial.

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.

Sleep insufficiency and bedtime irregularity in children with ADHD: A population-based analysis.

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.

A deep transfer learning approach for sleep stage classification and sleep apnea detection using wrist-worn consumer sleep technologies.

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.

Impaired 24-h activity patterns are associated with an increased risk of Alzheimer's disease, Parkinson's disease, and cognitive decline.

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.

Circadian protein expression patterns in healthy young adults.

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.

The impact of screen use on sleep health across the lifespan: A National Sleep Foundation consensus statement.

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.