Abstract Introduction Closed-loop auditory stimulation is able to enhance slow wave activity (SWA) on the electroencephalogram (EEG), however individual responses can vary. We investigated whether pre-sleep physiological features could identify who benefits most from the stimulation and investigated relationships between stimulation responsiveness, sleep enhancement, and next-day cognitive performance. Methods Twenty-eight healthy adults (ages 19-40, mean 27±5 years) experiencing mild sleep restriction underwent three visits, consisting of adaptation followed by randomized stimulation and sham nights. Pre-sleep resting EEG and HRV (8 minutes) were captured to establish baseline brain and cardiac activity before lights-off. During sleep, a phase-locked loop detected slow oscillations in the upstate and triggered 50-ms pink noise bursts for the first five hours. Word-pair recall and psychomotor vigilance task were administered at 1, 4, 7, and 10 hours post-wake. Machine learning models utilizing EEG spectral features and transfer learning from pre-trained sleep architectures were fine-tuned to predict responsiveness. The scores were calculated based on a leave-one-subject-out cross-validation approach. Results Auditory stimulation enhanced SWA in 26 out of 28 subjects. Pre-sleep alpha power positively correlated with SWA enhancement (r=0.436, p< 0.01), as did theta power (r=0.329, p< 0.01) and sleep onset latency (r=0.429, p< 0.01). Delta power showed negative associations (r=-0.299, p=0.01). Individuals with higher HRV, longer sleep onset, and who had less slow oscillation during sleep demonstrated more enhancement. Subject-level temporal embeddings from pre-sleep EEG predicted SWA responsiveness with 80% accuracy (AUC=0.93) and memory enhancement with 90% accuracy (AUC=0.92). Physiological responders showed trends toward improved memory retention at mid-day timepoints (4-7 hours post-wake, p=0.07-0.08) compared to non-responders. Also, our observations show that higher pre-sleep heart rate variability correlated with greater SWA enhancement and predicted better sustained attention at 7-10 hours post-wake. Conclusion Pre-sleep features reliably predict individual responsiveness to auditory stimulation and, to some degree, the associated cognitive benefits. Higher HRV, elevated alpha activity, prolonged sleep onset, and a lower number of slow oscillations indicate a greater enhancement of SWA. This helps to identify individuals who need and would benefit most from intervention. Support (if any) Alzheimer's Association, Michael J. Fox Foundation, CurePSP Sleep Contributions to Neurodegeneration Grant Program (SCN-25-1470707).

Abstract Introduction Little is known about circadian rhythm disruption and Alzheimer’s disease (AD) biomarkers in adults with Down syndrome (DS). The study aim was to examine the association of 24-hour rest-activity rhythm (RAR) with plasma Amyloid-Tau-Neurodegeneration (ATN) biomarkers and amyloid PET in adults with DS. Methods Cross-sectional study of adults with DS (25–61 years) enrolled in the Alzheimer Biomarker Consortium-Down syndrome who underwent wrist-worn actigraphy, plasma ATN and amyloid PET assessment. Primary variables were measures of 24-hour RAR: interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), L5 (least active 5-hour period) and M10 (most active 10-hour period). Secondary measures included: coefficient of variation of total sleep time, sleep midpoint, and sleep efficiency; and the sleep regularity index (SRI). ATN biomarkers included amyloid beta 42/40 ratio, phosphorylated-tau 181 (pTau181), and neurofilament light chain. Amyloid PET were harmonized using centiloids. Analyses were performed using linear regressions. Covariates included age, sex, intellectual disability level, site, and obstructive sleep apnea severity. Results Of 91 participants, mean (SD) age was 39.5 (8.6) years and 43% were female. After adjustment, higher IV (indicating fragmentation of RAR in a 24-hour period) was associated with increased levels of pTau181 [standardized beta (β)=0.22, p=0.02]. Higher RA (indicating robust RAR) and higher SRI (indicating consistent and regular sleep patterns) were associated with lower pTau181 (β = -0.21, p=0.03 and β = -0.21, p=0.03, respectively). In the subsample of participants who had amyloid PET data available at the time of analysis (n = 50), higher IV was associated with increased centiloids (β=0.22, p=0.04). Conclusion These findings suggest that circadian rhythm disruption (RAR) is associated with plasma and imaging biomarkers of AD. Further research is needed to understand whether interventions to strengthen circadian rhythms reduce AD biomarker burden. Support (if any) This manuscript was supported by NIH grant #T32HL007909 and #F31AG085730. Data was collected as part of the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) and a related Lifestyle R01 study that are funded by the National Institute on Aging and the National Institute for Child Health and Human Development (U01AG051406, U01AG051412, U19AG068054; R01AG070028) and the Investigation of Co-occurring conditions across the Lifespan to Understand Down syndrome (NIH INCLUDE Project).

Abstract The interplay between sleep slow oscillations (SOs), spindles, and autonomic activity is thought to be crucial for sleep-dependent memory consolidation, yet the precise mechanisms remain unclear. In this randomized, single-blind, crossover study of 20 healthy young adults (25 ± 4 years, 75% female), we investigated whether one night of closed-loop acoustic stimulation of sleep slow waves during non-rapid eye movement sleep stages 2 and 3 enhanced memory retention at a paired word-associates task by modulating these neural and autonomic processes, compared to a sham condition. We found that memory enhancement was associated with two tightly coupled mechanisms: increased spindle nesting with SOs (0.5 - 1.5 Hz) relative to delta waves (δ, >1.5 - 4 Hz), and elevated parasympathetic activity measured by heart rate variability during SWS. Critically, the SO/δ-spindle nesting ratio, not absolute SO-spindle nesting, predicted memory performance, suggesting that an optimized relative balance between SO and δ wave influences on spindle activity drives consolidation. Both the SO/δ-spindle nesting ratio and parasympathetic activity predicted memory retention and were strongly correlated, pointing to a potential mechanistic link. Findings suggest that acoustic stimulation may enhance memory consolidation by optimizing the coordination between sleep oscillatory networks and autonomic activity.

BACKGROUND:Time-restricted eating has gained attention for its potential cardiometabolic health benefits. Existing time-restricted eating approaches may have limited adherence and sustainability due to fixed fasting windows with prolonged fasting duration before sleep, or they involve self-selected fasting windows without specifying the duration relative to sleep, a critical period for cardiometabolic regulation. We hypothesized that an individualized approach that extended overnight fasting duration by 3 hours in alignment with habitual sleep time (last meal ≥3 hours before sleep) would enhance nighttime autonomic balance, decrease blood pressure and heart rate, increase blood pressure per hour dipping, and glucose regulation compared with a control group maintaining habitual eating patterns. METHODS:In this randomized parallel-arm controlled trial, 39 overweight/obese participants (36-75 years) completed either an extended overnight fasting intervention (13-16-hour fasting) or a control condition (habitual fast of 11-13 hours). Both groups dimmed lights 3 hours before bedtime. The intervention duration was 7.5 weeks. RESULTS:Compared with control, extended overnight fasting intervention significantly improved the coprimary outcome of nighttime dipping of diastolic blood pressure, but not the Matsuda Index of insulin sensitivity. extended overnight fasting improved secondary measures of nighttime autonomic function and morning oral glucose tolerance, including lower nighttime heart rate, higher heart rate variability, lower nighttime cortisol, and during the Oral Glucose Tolerance Test, lower glucose level, and higher 30-minute insulinogenic index, indicating improved acute insulin response. CONCLUSIONS:Extending overnight fasting duration by 3 hours in alignment with sleep improved cardiometabolic health in middle-aged/older adults by strengthening coordination between circadian- and sleep-regulated autonomic and metabolic activity. This sleep-aligned time-restricted eating approach represents a novel, accessible lifestyle intervention with promising potential for improving cardiometabolic function.

OBJECTIVE:Fatigue is a prevalent and debilitating symptom for patients with rheumatoid arthritis (RA). Although patients and rheumatologists often attribute fatigue to inflammation, other factors such as sleep disturbances are frequently overlooked. This study aims to explore the relationship between subjective (self-reported) and objective (actigraphy based) sleep parameters and self-reported fatigue in patients with RA. METHODS:This cross-sectional analysis included data from 48 adult patients with RA from a single academic rheumatology practice. Sleep data were obtained daily over 14 days with actigraphy (objective) and the Karolinska Sleep Diary (subjective). Fatigue was assessed using the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue computerized adaptive test. Spearman's correlations and linear regression analyses were used to examine associations between sleep parameters and fatigue, adjusting for swollen joint count, pain intensity, and symptoms of depression. RESULTS:Subjective sleep parameters showed significant correlations with PROMIS fatigue. Longer total sleep time (ρ = -0.4, P < 0.01), higher sleep efficiency (ρ = -0.42, P < 0.01), and better sleep quality (ρ = -0.5, P < 0.01) were associated with lower levels of fatigue. Objective actigraphy-based sleep parameters were not significantly associated with PROMIS fatigue. Separate linear regression models demonstrated that each subjective sleep parameter remained significantly associated with fatigue after adjusting for covariates. CONCLUSION:Self-reported poor sleep duration, efficiency, and quality were significantly associated with fatigue in patients with RA, whereas objective actigraphy-based sleep parameters were not, supporting the integration of self-reported assessment of sleep disturbances into RA treatment plans to improve patient outcomes.

Circadian rhythms play a fundamental role in regulating cardiometabolic function, with food intake serving as a key metabolic synchronizer. Emerging evidence suggests that time-restricted eating maybe a promising approach for improving cardiometabolic health. In this study we investigated the effect of a 6-week extended overnight fasting (EOF) intervention on glucose regulation, nighttime heart rate variability (HRV) and day-to-night change in blood pressure (BP) and heart rate (HR) in middle and older aged adults, a population particularly vulnerable to cardiometabolic disruptions. Twenty-six adults (age: 58±8 years, BMI: 31±4 kg/m², post-menopausal if female, HbA1c < 6.5%) with a habitual overnight fast (OF) of ≤13 hours were randomized to either a 6-week EOF intervention (n=14, 57±7 years, 10 female) or control group (n=11, 60±9 years, 8 female). The EOF group had OF extended by 3 hours (12-16 hours OF) with the last meal consumed ≥3 hours before bedtime, while controls maintained their usual eating schedule. Participants were instructed to maintain their habitual sleep schedule, caloric and macronutrient intake throughout the study period. Assessments occurred during 3-day/2-night laboratory stays at baseline and post-intervention, including a morning 3-hour oral glucose tolerance test (OGTT), overnight HRV, 16.5-hour ambulatory BP and HR monitoring initiated in the afternoon, and polysomnography. Between-group differences in metabolic parameters, nighttime HRV, day-to-night BP and HR dipping, and sleep parameters were analyzed with age as a covariate. In response to the OGTT, the EOF group showed lower glucose levels (p< 0.0001) and higher 30-minute insulinogenic index (p=0.032), a measure of beta-cell function. EOF group exhibited reduced low-frequency to high-frequency ratio from HRV (p< 0.0006), and showed heightened day-to-night diastolic BP and HR dipping (p=0.042 and p=0.028, respectively). Sleep architecture remained unchanged between groups. Six weeks of EOF improved regulation of glucose, nighttime autonomic balance and day-to-night dipping of diastolic BP and HR in middle and older-aged adults. These findings highlight the importance of the inclusion of circadian-aligned eating patterns in lifestyle interventions to enhance cardiometabolic function and health, particularly in older adults. National Heart Lung and Blood Institute (R01HL140580) and National Institute of Aging (P01AG011412).

Recent studies suggest the duration of the overnight fast and how late we eat is related to health. The goal of this analysis was to examine the relationship between time of eating with blood pressure (BP) measures including mean arterial pressure (MAP) which is a key factor in supplying blood to body tissues. We will test the hypothesis that a longer overnight fasting period and longer duration between last meal and bedtime will be associated better BP measures in healthy middle-age and older adults. This cross-sectional study recruited adults aged 35-75 years from the community. Participants had height, weight, %body fat (Bioelectrical Impedance Analysis), HbA1c (point of care) and blood pressure measured (average of 3 daytime measures after 5-minute seated) and completed questionnaires related to demographics, sleep and eating habits. Exposure variables included overnight fast duration (OF) and duration between last meal and bedtime (LMBT). The outcome variables were mean arterial pressure (MAP), systolic (SBP) and diastolic DBP) blood pressure. Multivariate regression models were used controlling for age, sex, %body fat, sleep duration. Data are from 405 participants with a mean (±stdev) age 52.09±10.2 years and 75.1% female. Means (±stdev) were: 30.4±6 kg/m2 for body mass index, 5.5±0.4% for HbA1c, 36.7±9.1% for % body fat, 125.05±17.5 mmHg for SBP, 80.67±10.3 mmHg for DBP, and 95.5±11.9 mmHg for MAP. Mean OF duration was 11.85±1.7 hours and LMBT duration was 2.64±1.4 hours. OF was negatively associated with SBP (r -0.11, p=0,03) and MAP (r -0.103, p=0.04) which was no longer significant after adjustment. The LMBT duration was negatively related to SBP (r -.013 p=0.009), DBP (r -0.10 p=0.03) and MAP (r -0.12, p=0.013). However, after adjustment only SBP and MAP remained significant (b=-1.42 p= 0.013 and b=-0.84, p=0.034, respectively). These results suggest that in middle-aged and older adults that a longer interval between last meal and bedtime is associated with better blood pressure measures. National Heart Lung and Blood Institute (R01HL140580) and National Institute of Aging (P01AG011412)

Introduction:Prior data suggest that higher nocturnal heart rate may represent a marker of cardiometabolic disease risk in nonpregnant adults. Data on nocturnal heart rate and pregnancy outcomes are limited. We sought to assess the association of maternal nocturnal heart rate with adverse pregnancy outcomes. Methods:This is a secondary analysis of nulliparas in a prospective cohort at eight US sites undergoing a home sleep study using the Embletta-Gold device with bipolar electrocardiogram at baseline (60-156 weeks) and follow-up (220-316 weeks) visits. Exposures were mean, minimum, and maximum nocturnal heart rate at baseline and follow-up (analyzed separately). Outcomes of interest were gestational diabetes, hypertensive disorders of pregnancy, preterm birth, small-for-gestational age, and stillbirth. Multivariable logistic regression models estimated the odds of each outcome, except for stillbirth due to low frequency, per each 5-beat higher nocturnal heart rate, adjusted for possible confounders. Results:Among 2952 eligible nulliparas, 30% experienced an adverse pregnancy outcome. We identified higher adjusted odds of gestational diabetes (minimum nocturnal heart rate mean ± standard deviation, gestational diabetes vs. no gestational diabetes: 49 ± 10 vs. 46 ± 11; adjusted odds ratio [aOR] 1.15, 95% confidence interval [CI] 1.03-1.29) and hypertensive disorders of pregnancy (48 ± 11 vs. 46 ± 11; aOR 1.05, 95% CI 1.01-1.10) for each 5-beat higher minimum nocturnal heart rate at baseline; adjusted odds of gestational diabetes were also higher at baseline and follow-up for mean and maximum nocturnal heart rate. At follow-up, we identified lower adjusted odds of small-for-gestational age for each 5-beat higher mean (76 ± 10 vs. 78 ± 9; aOR 0.83, 95% CI 0.78-0.88) and minimum nocturnal heart rate (48 ± 12 vs. 51 ± 13; aOR 0.90, 95% CI 0.86-0.94). Conclusion:Higher mean, minimum, and/or maximum nocturnal heart rate in pregnancy were associated with higher odds of hypertensive disorders of pregnancy and gestational diabetes. This may reflect higher sympathetic and/or decreased parasympathetic activity in affected gravidas. Conversely, lower mean and minimum nocturnal heart rate in late pregnancy were associated with higher odds of small-for-gestational age, which may be reflective of maladaptive hemodynamic changes in affected gravidas.

Obstructive sleep apnea (OSA) may disrupt autonomic and vascular control, affecting skin temperature variability (STV). We aimed to assess whether STV (measured at distal and proximal sites) is associated with OSA severity (apnea-hypopnea index [AHI] and percent of sleep time with oxygen saturation below 90

Sleep interventions targeting slow-wave activity (SWA) show heterogeneous effects across individuals. We investigated whether pre-sleep brain states predict responsiveness to auditory stimulation and associated cognitive benefits. Twenty-eight healthy adults (19-40 years) completed three overnight laboratory visits under mild sleep restriction. Pre-sleep EEG recordings captured spectral band power before each night. Participants received auditory stimulation or sham on two randomized nights with polysomnography monitoring. Memory recall and sustained attention were assessed at multiple timepoints the following day. Machine learning models using normalized EEG features and transfer learning with pre-trained sleep architectures (SleepNet, DeepSleepNet, TinySleepNet) predicted responsiveness. Auditory stimulation significantly enhanced SWA ( p < 0.01) in over 90% of participants. Pre-sleep alpha and theta power correlated with SWA enhancement (alpha: r = 0.436; theta: r = 0.329; both p < 0.01), as did sleep onset latency ( r = 0.429, p < 0.01). Temporal embeddings derived from 8 minutes of pre-sleep EEG before lights off predicted individual responsiveness to auditory stimulation with 80% accuracy (AUC = 0.93). Pre-sleep brain state determines responsiveness to auditory stimulation, with individuals exhibiting longer sleep onset latency showing greater SWA enhancement. Tailoring pre-sleep interventions based on these predictive features may optimize brain receptivity to auditory stimulation during sleep.

Prior data suggest nocturnal heart rate (NHR) may represent a marker of cardiometabolic disease risk in non-pregnant adults, but data on NHR and pregnancy outcomes are limited. We sought to assess the association of NHR with gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP). This is a secondary analysis of nulliparas enrolled in a prospective observational cohort at 8 clinical sites who completed a home sleep study using the Embletta-Gold device with bipolar electrocardiogram at baseline (60-136 weeks) and follow-up visits (220-296 weeks). We excluded those with chronic hypertension or pregestational diabetes. The primary exposure was the mean NHR at baseline and follow-up (analyzed separately). Secondary exposures were the minimum and maximum NHR at each visit. The outcomes were GDM and HDP. Independent samples t-tests compared each exposure among gravidas with and without the outcomes of interest. Multivariable logistic regression models estimated the odds of each outcome per 5-beat increase in NHR at baseline and follow-up. Among 2,952 eligible nulliparas, 4.1% (118/2911) developed GDM and 13.6% (392/2890) developed HDP. The mean (standard deviation) for the mean, minimum, and maximum NHR was 71 (8), 46 (11), and 102 (14) at baseline, and 78 (9), 51 (13), and 108 (15) at follow-up. Gravidas who developed GDM had higher mean, minimum, and maximum NHR at baseline and follow-up than unaffected gravidas (p ≤ 0.01, Table), with each exposure associated with higher adjusted odds of GDM. Gravidas who developed HDP also had higher mean NHR (baseline and follow-up), higher minimum NHR (baseline), and higher maximum NHR (follow-up) (p < 0.01) than those without HDP. For each 5-beat increase in mean NHR at the baseline visit, the adjusted odds of GDM and HDP were higher by 39% and 10%, respectively, with similar increased odds at follow-up. Higher mean, minimum, and maximum NHR in pregnancy appear to be associated with higher odds of GDM and HDP. This may reflect increased sympathetic and/or decreased parasympathetic activity in affected gravidas.

Abstract Introduction Obstructive sleep apnea (OSA) is associated with altered cognitive function and dementia, but the mechanisms underlying these associations remain unclear. One proposed mechanism is that OSA, by chronically fragmenting sleep, decreases the number and activity of sleep spindles, which are important for memory consolidation. Few studies have examined sleep spindle characteristics in people with OSA and with conflicting results. This study aims to examine sleep spindle characteristics in people with and without OSA from a multicenter community-based prospective cohort study, the Sleep Heart Health Study (SHHS). Methods The analysis was conducted on 5804 subjects of which 2830 had no OSA (apnea-hypopnea index (AHI) < 5, 61±12 years, 65% women), and 2974 had OSA (AHI ≥5, 65±11 years, 39% women). Spindle density (n/min) and frequency (Hz) were measured during non-rapid eye movement stage 2 from the left central electroencephalographic derivation. Arousal index (AI, n/hr) was used as a measure of sleep fragmentation and Epworth Sleepiness Scale (ESS) as a measure of subjective daytime sleepiness. Linear regression models adjusted for age, sex, BMI and education level were used to compare spindle features in OSA vs non OSA, and to examine the association between spindle features with AHI, oxygen desaturation degree and duration, AI and ESS in OSA group. Results In fully adjusted models, spindle density was lower in OSA compared to no OSA (-0.067 spindles per minute, p=< 0.001). In OSA group, lower sleep spindle density was associated with higher AHI (β= -0.003, p=< 0.001), higher AI (β= -0.002, p=0.020) and higher ESS score (β= -0.007, p=0.007) indicating higher daytime sleepiness. Spindle density was not associated with oxygen desaturation degree or duration. Spindle frequency was similar between OSA and non OSA. Conclusion These findings indicate that spindle density is reduced in people with OSA compared to those without OSA, and this reduction correlates with OSA severity (AHI) and levels of daytime sleepiness. Reduced spindle density in OSA might contribute to OSA-related cognitive impairment and future work is needed to investigate the relationship between reduced spindle density and cognitive function in OSA. Support (if any) Center for Circadian and Sleep Medicine

Substantial evidence suggests that the circadian decline of core body temperature (CBT) triggers the initiation of human sleep, with CBT continuing to decrease during sleep. Although the connection between habitual sleep and CBT patterns is established, the impact of external body cooling on sleep remains poorly understood. The main aim of the present study is to show whether a decline in body temperatures during sleep can be related to an increase in slow wave sleep (N3). This three-center study on 72 individuals of varying age, sex, and BMI used an identical type of a high-heat capacity mattress as a reproducible, non-disturbing way of body cooling, accompanied by measurements of CBT and proximal back skin temperatures, heart rate and sleep (polysomnography). The main findings were an increase in nocturnal sleep stage N3 (7.5 ± 21.6 min/7.5 h, mean ± SD; p = 0.0038) and a decrease in heart rate (− 2.36 ± 1.08 bpm, mean ± SD; p < 0.0001); sleep stage REM did not change (p = 0.3564). Subjects with a greater degree of body cooling exhibited a significant increase in nocturnal N3 and a decrease in REM sleep, mainly in the second part of the night. In addition, these subjects showed a phase advance in the NREM-REM sleep cycle distribution of N3 and REM. Both effects were significantly associated with increased conductive inner heat transfer, indicated by an increased CBT- proximal back skin temperature -gradient, rather than with changes in CBT itself. Our findings reveal a previously far disregarded mechanism in sleep research that has potential therapeutic implications: Conductive body cooling during sleep is a reliable method for promoting N3 and reducing heart rate.

To characterize sleep disturbance in patients with established rheumatoid arthritis (RA) and explore the relationship between sleep and mechanisms of central nervous system pain regulation. Forty-eight RA participants completed wrist-worn actigraphy monitoring and daily sleep diaries for 14 days to assess sleep-wake parameters. Participants underwent quantitative sensory testing to assess pressure pain thresholds, temporal summation, and conditioned pain modulation. Data were analyzed using descriptive statistics, Spearman’s correlation, and multivariable median regression analyses. Median actigraphy and sleep diary derived sleep duration was 7.6 h (interquartile range (IQR) 7.0, 8.2) and 7.1 h (IQR 6.7, 7.6), respectively. Actigraphy based sleep fragmentation (rho = 0.34), wake after sleep onset (rho = 0.36), and sleep efficiency (rho = -0.32) were each related to higher temporal summation values in unadjusted analyses, but these relationships did not persist after controlling for age, body mass index, disease duration, and swollen joint count. No significant relationships were observed between sleep with pressure pain thresholds and conditioned pain modulation. Actigraphy and sleep diary monitoring are well tolerated in established RA patients. Future investigations should include both subjective and objective assessments, as they may provide information relating to different components and mechanisms.

Introduction:Fatigue, brain fog, and sleep disturbance are among the most common symptoms of postacute sequelae of SARS-CoV-2 infection (PASC). We sought to determine the impact of sleep disruption on cognition and quality of life in patients with neurologic manifestations of PASC (Neuro-PASC). Methods:Thirty-nine patients were recruited from Neuro-COVID-19 clinic. Mean age was 48.1 years, 71.8% were female, and 82% were never hospitalized for COVID-19. Patients were evaluated via clinical assessment, quality-of-life measures in domains of cognitive function, fatigue, sleep disturbance, anxiety, and depression, NIH Toolbox cognitive tests, and 7 days of wrist actigraphy. Results:The median number of neurologic symptoms attributed to PASC was 6, with brain fog being the most common in 89.7%. Regarding non-neurologic symptoms, 94.9% complained of fatigue and 74.4% of insomnia. Patients reported significant impairment in all quality-of-life domains and performed worse in a task of attention compared to a normative US population. Actigraphy showed Neuro-PASC patients had lower sleep efficiency, longer sleep latency (both p < 0.001), and later sleep midpoint (p = 0.039) compared to 71 age-matched healthy controls with no PASC history. Self-reported cognitive symptoms correlated with the severity of fatigue (p < 0.001), anxiety (p = 0.05), and depression (p < 0.01). Objective evidence of sleep disruption measured by wakefulness after sleep onset, sleep efficiency, and latency were associated with decreased performance in attention and processing speed. Conclusion:Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep disruption on the cognitive function and quality of life of patients with PASC.

Abstract Introduction The nesting of electroencephalographic (EEG) sleep slow oscillations (SOs) to spindles has been shown to be important for sleep-dependent memory consolidation. However, recent evidence indicates that a higher proportion of SOs nested to spindles, relative to δ waves, might be even more critical for sleep-dependent memory consolidation. Acoustic stimulation during slow wave sleep has been shown to be effective in improving memory consolidation. Here, we examined the contribution of SOs nested to spindles relative to δ waves on sleep-dependent declarative memory consolidation associated with acoustic stimulation. Methods Twenty subjects (18-35 years, 75% females) participated in a randomized cross-over study. At each visit participants received either stimulation (stim) or sham following an adaption night. Stim occurred in blocks of 5 pulses (ON intervals) followed by a period of equal length with no stimulation (OFF intervals). Participants learned 40 Arabic-English word pairs and were tested before sleep and after sleep in the morning and again in the afternoon. Detection of SOs (< 2 Hz), δ waves (2-4 Hz), spindles (11-16Hz), and the ratio (%) of spindles nested to SO over δ waves (SO/δ Nesting Index) were calculated during ON intervals for stim and sham conditions. Results Overnight mean (SD) percentage change in word recall between conditions was similar in the morning (stim 6(3)%, sham 4(6)%, p=0.68), but was higher in the afternoon in stim compared to the sham condition (stim 10(4)%, sham 4(6)%, p=0.02). The SO/δ Nesting Index was higher in stim compared to the sham condition (stim 21(13)%, sham 13(10%), p=0.004). Within-subject improvement from sham to stim condition in afternoon memory was associated with a greater change in SO/δ Nesting Index (R=0.63, p=0.03), this association was not observed for spindles nested to SOs (R=0.33, p=0.202) or spindles nested to δ waves (R=-0.18, p=0.811). Conclusion Enhancement of memory consolidation with acoustic stimulation may be dependent on its ability to increase SOs nested to spindles relative to δ waves. Dynamic changes in the relationships between SOs, δ waves and spindles can help inform novel EEG-derived markers and targets to enhance sleep-dependent memory consolidation. Support (if any) DARPA award W911NF-16- 2-0021

Abstract Introduction Motion-based wearable sensors, typically on wrist, have long been used for free-living sleep detection and quantification. However, it is hard to differentiate sleep from sedentary awake time by immobility alone. Vital signs, like heart rate and respiration rate, can greatly enhance determination of wake-sleep state, and are easily monitored with newer wearable sensors. Deep learning techniques are particularly adept at learning labeled physiological states. By combining movement plus vital signs in a deep neural network algorithm, improved sleep detection, fragmentation and sleep staging should be possible compared to activity alone. We report on performance of a deep learning sleep detection and REM/NREM algorithm providing 24-hour evaluation with high specificity using data from a torso-wearable patch sensor as compared to polysomnography (PSG). Methods Twenty-six healthy adults (mean age 53.7 years, 81% female) contributed 150 nights of PSG during laboratory visits, during which participants simultaneously wore a multi-day skin-adherent patch with continuous single-lead ECG and 3-axis accelerometer streams, as well as a wrist activity monitor. A pre-trained deep neural network algorithm generated epoch-level Wake/REM/NREM classification (Sleep equals REM plus NREM) using vital signs and movement derived from the patch sensor ECG and accelerometer waveforms and was then compared to expert human staging of PSGs. The wrist actigraphy sleep-wake determinations (Actiware) were also compared to PSG. Results Data includes 900 hours sleeping and 139 hours awake, of which 195 hours of sleep were in REM state. Using patch data, the deep neural net algorithm achieved 92% sensitivity and 85% specificity to detect sleep as compared to PSG; REM was detected with 85% sensitivity and 97% specificity. By comparison, the wrist motion-based algorithm only exhibited 33% specificity and 95% sensitivity, essentially overcalling immobile wake as sleep. Conclusion Sleep evaluation in free-living environments with wearable sensors can be greatly improved over conventional motion-based wrist sensors by leveraging continuous vital signs. Deep learning-trained neural network algorithms are particularly effective for use with such data, as demonstrated with this algorithm. Support (if any) R01 HL140580 and P01 AG011412

SignificanceAmbient nighttime light exposure is implicated as a risk factor for adverse health outcomes, including cardiometabolic disease. However, the effects of nighttime light exposure during sleep on cardiometabolic outcomes and the related mechanisms are unclear. This laboratory study shows that, in healthy adults, one night of moderate (100 lx) light exposure during sleep increases nighttime heart rate, decreases heart rate variability (higher sympathovagal balance), and increases next-morning insulin resistance when compared to sleep in a dimly lit (<3 lx) environment. Moreover, a positive relationship between higher sympathovagal balance and insulin levels suggests that sympathetic activation may play a role in the observed light-induced changes in insulin sensitivity.