STUDY OBJECTIVES:Central (CSA) and obstructive (OSA) sleep apnea are common in heart failure (HF) patients, and treatment options depend on differential classification. To better characterize CSA vs OSA, we evaluated the discriminative value of established and novel polysomnographic traits in patients with HF. METHODS:We analyzed LOFT-HF trial participants with reduced left ventricular ejection fraction (LVEF) and apnea-hypopnea index (AHI) >15 events/hr. Central versus obstructive events were classified with expert investigator input. Multivariable logistic regression tested whether CSA (>50% of central/mixed events; otherwise OSA) was associated with increased loop gain, and other mechanistic traits (arousal threshold, collapsibility, muscle compensation). Mechanistic traits together with novel clinically-informed traits (e.g. event periodicity, flow limitation) were modeled to provide a probability score "Pr(CSA)" for objective CSA-versus-OSA discrimination. RESULTS:Among 122 HF patients (CSA:OSA=84:38), CSA was associated with higher loop gain (OR=4.4[2.2-9.1]), lower arousal threshold (6.4[2.4-16.9]), and greater muscle compensation (2.5[1.0-6.2]). Novel traits-greater event periodicity, larger event-related drive reduction, and reduced flow limitation-further improved discrimination (likelihood ratio test P=0.013 vs. mechanistic model). The final model (AUC=0.88) identified a subgroup enriched for true CSA (OR=8.4[3.5-20.1]). Sensitivity analyses using stricter central apnea-based definitions yielded similar or stronger associations with loop gain and modestly improved discrimination, although fewer individuals met CSA criteria. CONCLUSIONS:Patients with HF and CSA exhibit a distinct set of polysomnographic characteristics compared to OSA, which may facilitate their objective physiology-based characterization along the CSA-OSA continuum.

Positive airway pressure (PAP) therapy is the gold standard treatment for obstructive sleep apnea (OSA), yet adherence remains suboptimal. Mask leak is a common barrier, but current leak metrics don’t distinguish intentional from unintentional leak. We evaluated a novel “Real Leak” measure and compared its relationship to adherence with conventional leak metrics. We conducted a secondary analysis of the HomePAP trial, which randomized adults at high risk for OSA to home sleep apnea testing or in-laboratory polysomnography, followed by PAP initiation. Real Leak was calculated by subtracting mask-specific intentional leak from device-reported Average Leak, essentially representing unintentional leak over 1 month. PAP adherence was defined as ≥ 4 h/night on ≥ 70

Background: Poor prenatal sleep health is associated with greater gestational weight gain, but the contributions to longer-term maternal weight retention remain unclear. Purpose: To examine associations between prenatal sleep health across multiple domains and maternal weight retention 2 to 7 years after a first birth. Methods: Participants were from the nuMoM2b-Heart Health Study. Self-reported sleep was assessed during early (6 to 13 6/7 weeks) and mid-pregnancy (22 to 28 6/7 weeks) across six domains: regularity, quality, sleepiness, timing, efficiency, and duration. A multidimensional sleep health (MSH) score reflected the number of domains meeting healthy thresholds. Outcomes included maternal weight retention, total and substantial (>11 lbs.), from pre-pregnancy to 2 to 7 years after a first birth. Associations were estimated using adjusted linear regression for total weight retention and Poisson regression with robust variance for substantial weight retention. Results: The sample included 3,661 individuals with data in early (n = 2,962) and mid-pregnancy (n = 3,210). In early pregnancy, healthy sleep duration was associated with lower total weight retention, whereas healthy sleep regularity was unexpectedly associated with greater retention. In contrast, during mid-pregnancy, a higher MSH score was associated with a lower risk of substantial weight retention (RR = 0.96, 95% CI: 0.93 to 0.99). Healthy sleep duration and quality were the two individual domains associated with lower weight retention (2 to 3 lbs.). Conclusions: In a prospective cohort of pregnant nulliparous individuals, healthy prenatal sleep, particularly during mid-pregnancy, was associated with less maternal weight retention 2 to 7 years after delivery. Future studies should estimate the causal effects of sleep health on long-term maternal weight retention.

Daylight saving time (DST) transitions lead to disruptions in circadian rhythm, and studies have identified an association between DST transitions and cardiovascular events. Changes in retinal microvasculature can reflect systemic cardiovascular health. This study investigated the relationship between DST transitions and retinal vascular disease. Patients aged 18-64 years old enrolled in the Merative MarketScan Commercial Database between 2012 and 2014 were identified. Incidence of new diagnosis of retinal artery occlusion (RAO), retinal vein occlusion (RVO), proliferative diabetic retinopathy (PDR), and neovascular age-related macular degeneration (nvAMD) were determined after autumn DST transition, spring DST transition, and a summer or winter control period. Survival analysis via Kaplan Meier curves and Cox proportional hazards models were used to determine the effect of variables of interest on new-onset retinal vascular disease during one-week and one-month periods following DST transition. We identified 12,640,343 patients who met inclusion criteria. With a summer control period, there was lower risk of RVO (adjusted hazard ratio [98.75% confidence interval]: 0.84 [0.72-0.99], P = 0.033), and PDR (0.83 [0.73-0.94], P = 0.001) in the month following autumn DST transition. There was higher risk of PDR (1.34 [1.19-1.50], P<0.0001) and nvAMD (1.24 [1.03-1.50], P = 0.015) in the month following spring DST transition. With a winter control period, there was lower risk of RAO (0.75 [0.60-0.94], P = 0.005), RVO (0.66 [0.53-0.82], P<0.0001), PDR (0.61 [0.51-0.72], P<0.0001), and nvAMD (0.64 [0.49-0.83], P < 0.0001) in the month following autumn DST transition. Further investigation into the effects of circadian disruption on ocular health is warranted.

Importance:Sleep-wake disturbances in midlife are common and potentially modifiable contributors to long-term brain health, yet primary care lacks a brief, validated tool that reliably identifies adults with early cognitive vulnerability. Objective:To evaluate associations between commonly used sleep questionnaires and cognitive impairment among midlife primary care patients. Design Setting and Participants:Cross-sectional analysis of baseline data from the MidCog cohort, an observational study of English-speaking adults aged 35 to 64 years receiving primary care at academic practices or federally qualified health centers in the Chicagoland area. Exposures:Five validated sleep questionnaires were used to assess distinct sleep-wake disturbance phenotypes: (A) unsatisfactory sleep (PROMIS Sleep Disturbance T-score >55), (B) short sleep duration (<6 hours; Munich Chronotype Questionnaire), (C) obstructive sleep apnea (OSA) risk (STOP-Bang ≥3), (D) insomnia symptoms (Insomnia Severity Index ≥15), and (E) poor multidimensional sleep health (RU-SATED ≤6). Main Outcomes and Measures:The primary outcome was cognitive impairment defined as an age- and education-adjusted NIH Toolbox Cognition Battery (NIHTB-CB) Fluid Composite T-score <40 (>1 SD below the population mean). Cognitive impairment defined by the Montreal Cognitive Assessment (MoCA) score <23 served as the secondary outcome. Logistic regression estimated adjusted odds ratios (aOR), controlling for age, sex, education, body mass index, hypertension, hypercholesterolemia, diabetes, smoking, depressive symptoms, and recruitment site. Results:Among 646 participants (mean [SD] age, 52.3 [8.1] years; 62.4% female; 38.0% non-Hispanic Black, 38.4% non-Hispanic White, 16.0% Hispanic), cognitive impairment was present in 18.7% by NIHTB-CB and 22.3% by MoCA. Among five sleep-wake disturbance phenotypes evaluated, only poor multidimensional sleep health was consistently associated with cognitive impairment after multivariable adjustment (NIHTB-CB: adjusted OR [95% CI] = 2.03 [1.25-3.26]; MoCA: 1.98 [1.20-3.26]). Conclusions and Relevance:Poor multidimensional sleep health was associated with cognitive impairment in midlife primary care patients. Brief multidimensional sleep health screening may identify individuals with early cognitive vulnerability and represent a potential strategy for targeting sleep-focused interventions to promote long-term brain health. Key Points:Question: Among commonly used brief sleep questionnaires, which measure, if any, best identifies midlife primary care patients at risk of early cognitive vulnerability?Findings: In this cross-sectional study of 646 primary care patients aged 35-64 years, poor multidimensional sleep health assessed using the RU-SATED questionnaire was the only sleep-wake disturbance phenotype consistently associated with cognitive impairment across two cognitive measures (NIH Toolbox Cognitive Battery and Montreal Cognitive Assessment).Meaning: Brief multidimensional sleep health screening may help identify midlife adults with sleep-related early cognitive vulnerability in primary care and may represent a potential target for sleep-focused interventions to promote long-term brain health.

BACKGROUND AND OBJECTIVES:There is a paucity of research on the role of circadian rhythm disruption in Alzheimer disease (AD)-related cognitive impairments in adults with Down syndrome (DS). The aim of this study was to examine the association of the 24-hour rest-activity rhythm with cognition, dementia symptoms, and clinical AD status in adults with DS. METHODS:In this cross-sectional study, adults with DS aged 25-61 years in the Alzheimer's Biomarkers Consortium-Down Syndrome underwent wrist-worn actigraphy (≥4 days) and cognitive assessment. Primary variables included interdaily stability, intradaily variability, relative amplitude, most active 10-hour period (M10), and least active 5-hour period (L5). Secondary measures included coefficient of variation of total sleep time, sleep midpoint, sleep efficiency, and the sleep regularity index. Cognitive outcomes included modified Cued Recall Test (mCRT), Wechsler Block Design with Haxby Extension (Block Design), Purdue Pegboard, Cat and Dog Modified Stroop Task, DS Mental Status Examination (DSMSE), National Task Group-Early Detection Screen for Dementia (NTG-EDSD), Dementia Questionnaire for People with Learning Disabilities (DLD), and clinical AD status based on a case consensus process (stable vs mild cognitive impairment [MCI]/dementia). Linear and logistic regression models were adjusted for age, sex, intellectual disability level, site, and obstructive sleep apnea severity, with false discovery rate (FDR) correction. RESULTS:Of 115 participants (mean age 40.0 ± 9.2 years; 43.5% female), higher interdaily stability was associated with higher DSMSE scores B = 20.6 (95% CI 5.0-36.2). Higher intradaily variability was associated with worse cognitive performance and increased dementia symptoms: mCRT B = -9.2 (95% CI -15.2 to -3.1), Block Design B = -11.0 (95% CI -19.0 to -3.0), DSMSE B = -12.0 (95% CI -20.1 to -3.9), and DLD-cognitive B = 6.3 (95% CI 3.0-10.5). Lower M10 was associated with increased dementia symptoms: NTG-EDSD B = -0.004 (95% CI -0.008 to -0.001); DLD-cognitive B = -0.004 (95% CI -0.006 to -0.001), and DLD-social B = -0.003 (95% CI -0.005 to -0.0008). All associations remained significant after FDR correction (p < 0.05). Fifteen participants had MCI/dementia. Higher intradaily variability was associated with increased odds of MCI/dementia (OR: 1.45; 95% CI 1.04-2.29) although this was not significant after FDR correction. DISCUSSION:Fragmentation and low amplitude of the 24-hour rest-activity rhythm are associated with AD-related cognitive impairment, dementia symptoms, and increased odds of MCI/dementia in adults with DS. Circadian rhythm disruption may contribute to AD-related outcomes in adults with DS and potentially serve as a modifiable risk factor.

Background The joint effects of individual health behaviors on pregnancy health are rarely considered. We examined associations between combinations of first trimester health behaviors with adverse pregnancy outcomes (APOs) and blood pressure (BP) 2–7 years after delivery, and estimated the proportion of associations with later BP mediated by APOs. Methods Participants in the nuMoM2b Heart Health Study prospective cohort were included. Physical activity, diet, sleep duration, and smoking were scored using the Life’s Essential 8 framework. APOs included hypertensive disorders of pregnancy, preterm birth, gestational diabetes, small-for-gestational-age birth, or stillbirth. We constructed latent profiles of health behaviors using the Life’s Essential 8 scores. Risk of APOs and differences in continuous BP 2–7 years after delivery based on behavioral profiles were assessed with Poisson and linear regression. Mediation analysis examined the proportion of associations between behavioral profiles and BP mediated by APOs. Where appropriate, analyses were stratified by first trimester obesity status. Results Among 8700 nulliparas, four behavioral profiles were identified: Healthiest Behaviors (36%), Healthy Activity/Sleep with Poor Diet/Smoking (21%), Healthy Sleep Only (32%), and Least Healthy Behaviors (11%). Adjusted risk of APOs was 9–18% higher across the less healthy behavioral profiles compared to the Healthiest Behaviors profile. Among women without first trimester obesity, adjusted systolic and diastolic BP were 0.93 and 0.85 mmHg higher, respectively, 2–7 years after delivery in those with less healthy behavioral patterns. Associations were not significant among women with first trimester obesity. APOs did not mediate a significant proportion of the association with later-life BP. Conclusions Less healthy behavioral profiles in early pregnancy were associated with APOs and higher BP 2–7 years after delivery, and early pregnancy obesity was an important effect modifier for later-life BP. Associations with later BP were predominately direct, with no mediation through APOs.

OBJECTIVE: Restless legs syndrome (RLS) affects approximately one in five pregnant individuals and has been associated with adverse pregnancy outcomes and a fourfold increased risk of developing chronic RLS in later life.1,2 First-generation antihistamines (FGAs), commonly used during pregnancy to treat nausea, sleep disturbance, and allergy symptoms, have been shown to trigger or exacerbate RLS in non-pregnant adults.3 Because FGAs readily cross the blood-brain barrier and may interfere with dopaminergic signaling, they could plausibly increase susceptibility to RLS.2 However, whether initiation of FGAs during pregnancy is associated with gestational RLS is unknown. We therefore examined the association between FGA initiation during pregnancy and the prevalence of gestational RLS. STUDY DESIGN: We conducted a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), a prospective cohort of 10,038 nulliparous individuals with singleton pregnancies enrolled at 8 U.S. sites (10/1/2010-9/30/2013).4 Study visits occurred at 60-136 weeks (Visit 1), 160-216 weeks (Visit 2), and 220-296 weeks of gestation (Visit 3). At each visit, participants reported all prescription and overthe-counter medications taken either within the two months before conception (Visit 1) or since the preceding study visit (Visits 2 and 3), including medication name, start and stop dates, and reasons for use. We excluded individuals with a history of RLS diagnosis (n=178), missing medication data (n=381), or FGA use within 2 months before conception (n=170) (Figure S1). Early-pregnancy exposure was defined as initiating any FGA between conception and Visit 1. Mid-pregnancy exposure was defined as FGA use between Visits 2 and 3, the period immediately preceding RLS assessment. RLS symptoms were ascertained at early (after Visit 1) and mid-pregnancy (after Visit 3) using the International RLS Study Group diagnostic criteria;5 participants meeting all four criteria were classified as having RLS symptoms. Poisson regression with robust standard errors estimated relative risks for RLS symptoms by FGA exposure, adjusting for maternal age, gestational age at RLS assessment, early-pregnancy body mass index, iron supplementation, and tobacco use within one month. Sensitivity analyses further adjusted for nausea and vomiting severity and included comparator models evaluating second-generation antihistamine exposure. RESULTS: The early-pregnancy analysis included 6,641 participants (median age, 28 years [IQR, 23-31]; gestational age at assessment, 130 [116-136] weeks; Table 1). FGAs were initiated in 5.1% (339/6,641). The most commonly used FGAs were promethazine (41.3%), doxylamine (35.1%), and diphenhydramine (22.7%), most frequently taken for nausea or vomiting (66.4%) and sleep problems (18.0%). RLS symptoms were reported by 20.9% (71/339) of exposed and 16.4% (1,034/6,302) of unexposed participants. After adjustment, FGA initiation was associated with a higher prevalence of early-pregnancy RLS symptoms (RR=1.29; 95% CI, 1.04-1.59), corresponding to 4.5 additional cases per 100 exposed pregnancies (Table 2). The mid-pregnancy analysis included 6,585 participants, of whom 4.2% (275/6,585) reported FGA use between Visits 2 and 3. The most frequently used FGAs were diphenhydramine (40.0%), promethazine (32.4%), and doxylamine (28.4%), primarily used for nausea (44.7%) and sleep problems (26.5%). RLS symptoms, assessed at a median gestational age of 280 [266-290] weeks, were reported by 34.9% (96/275) of exposed and 29. 0% (1,830/6,310) of unexposed participants. Adjusted analyses showed a similar association (RR=1.20; 95% CI, 1.01-1.42), corresponding to 5.9 additional cases per 100 exposed pregnancies. Associations remained statistically significant after additional adjustment for nausea and vomiting severity (Table 2). In contrast, second-generation antihistamines were not statistically associated with RLS symptoms in adjusted models at either time point (Figure S2). CONCLUSION: In this prospective cohort of nulliparous pregnant individuals without prior RLS or preconception antihistamine use, initiation of first-generation antihistamines during pregnancy was associated with a higher prevalence of RLS symptoms in both early and mid-pregnancy, corresponding to approximately 4-6 additional cases per 100 exposed pregnancies. Second-generation antihistamines, which have less central nervous system penetration, were not statistically associated with RLS symptoms after adjusting for potential confounders; however, point estimates were similar in magnitude to those for first-generation antihistamines, and the null finding may represent type II error.

Background:We aimed to identify metabolites and create risk scores for insomnia symptoms in U.S. Hispanic/Latino adults. Methods:We analyzed data from 6,107 participants in the Hispanic Community Health Study/Study of Latinos, split into discovery (n=3,932) and replication datasets (n=2,175). Serum metabolites and the Women's Health Initiative Insomnia Rating Scale (WHIIRS) were collected at baseline. We examined the relationships between 768 metabolites and insomnia symptoms and suspected insomnia (WHIIRS≥9) using the discovery dataset, followed by replication. Metabolite risk scores (MRSs) were generated with LASSO regression and evaluated for replication. We assessed the relationships of replicated metabolite measures and MRS with sleep, cognitive, and psychological traits (cross-phenotypes). Findings:Nine metabolites were associated with insomnia symptoms in the discovery study, with two of these being replicated. Lower levels of hydrocinnamate and indolepropionate correlated with increased insomnia symptoms. We developed MRS for insomnia symptoms with replication. Various associations were observed between the two metabolites, 2 MRS, and cross-phenotypes. For instance, the WHIIRS MRS was associated with a higher risk of mild cognitive impairment (MCI) seven years later (OR:1.58, 95%CI:1.43-1.74 per 1 SD increase in MRS). Interpretation:The metabolomic profile associated with insomnia symptoms encompasses diet and gut microbiome metabolites. This study identified specific metabolites linked to insomnia that are also related to comorbidities, such as a higher risk of developing MCI during follow-up, suggesting a shared mechanism.

Background: Older adults frequently experience acute and long-term cognitive impairment following critical illness hospitalization in an intensive care unit (ICU). Delirium affects up to 80% of ICU patients and is linked to cognitive dysfunction and increased risk of cognitive decline associated with Alzheimer's disease and related dementias (ADRD). Sleep and circadian rhythm disturbances are present in about 75%-80% of ICU patients and may exacerbate delirium and undermine cognitive interventions. Nonpharmacological interventions such as earplugs, eye masks, and computerized cognitive training show promise in reducing delirium and improving sleep but have not been rigorously tested-separately or combined-in older adult ICU survivors. Moreover, prior studies have not leveraged chronotherapeutic timing to align cognitive training with individual circadian rhythms.Objectives: We propose a multimodal combination of sleep promotion intervention [SLEEP] and computerized cognitive training program timed daily according to individual chronotype [COG], to improve cognitive function in hospitalized older adult ICU survivors. The primary aim is to test the feasibility, acceptability, and preliminary separate and combined effects of SLEEP and COG [SLEEP, COG, SLEEP+COG] versus an active control condition [AC] in improving cognitive function after the intervention period. The secondary aims are to explore (1) circadian rhythm parameters of continuous body temperature to determine the optimal window for chronotherapeutic timing of cognitive interventions; (2) if the effects of each intervention on cognitive function are mediated by sleep and activity; (3) if biopsychosocial and clinical factors moderate the effects of each intervention on cognitive function; and (4) the effects of each intervention on cognitive function at 1, 6, and 12 months.Methods: After discharge from ICU, English- or Spanish-speaking older adult ICU survivors (n=100) are randomly assigned to 7 days of (1) SLEEP, (2) COG, (3) SLEEP+COG, or (4) AC. Cognitive function, delirium severity, sleep and circadian rhythms, patient-reported symptoms, and data regarding biopsychosocial and clinical factors are collected.Results: Results are pending study completion.Discussion: We aim to target sleep and circadian rhythm disturbances, mitigate ICU delirium, and reduce cognitive decline associated with ADRD. If hypotheses are supported, this combination of low-cost, nonpharmacological interventions could be integrated into standard care to accelerate cognitive recovery during hospitalization.

BACKGROUND:Older adults frequently experience acute and long-term cognitive impairment following critical illness hospitalization in an intensive care unit (ICU). Delirium affects up to 80% of ICU patients and is linked to cognitive dysfunction and increased risk of cognitive decline associated with Alzheimer's disease and related dementias (ADRD). Sleep and circadian rhythm disturbances are present in about 75%-80% of ICU patients and may exacerbate delirium and undermine cognitive interventions. Nonpharmacological interventions such as earplugs, eye masks, and computerized cognitive training show promise in reducing delirium and improving sleep but have not been rigorously tested-separately or combined-in older adult ICU survivors. Moreover, prior studies have not leveraged chronotherapeutic timing to align cognitive training with individual circadian rhythms. OBJECTIVES:We propose a multimodal combination of sleep promotion intervention [SLEEP] and computerized cognitive training program timed daily according to individual chronotype [COG], to improve cognitive function in hospitalized older adult ICU survivors. The primary aim is to test the feasibility, acceptability, and preliminary separate and combined effects of SLEEP and COG [SLEEP, COG, SLEEP+COG] versus an active control condition [AC] in improving cognitive function after the intervention period. The secondary aims are to explore (1) circadian rhythm parameters of continuous body temperature to determine the optimal window for chronotherapeutic timing of cognitive interventions; (2) if the effects of each intervention on cognitive function are mediated by sleep and activity; (3) if biopsychosocial and clinical factors moderate the effects of each intervention on cognitive function; and (4) the effects of each intervention on cognitive function at 1, 6, and 12 months. METHODS:After discharge from ICU, English- or Spanish-speaking older adult ICU survivors ( n =100) are randomly assigned to 7 days of (1) SLEEP, (2) COG, (3) SLEEP+COG, or (4) AC. Cognitive function, delirium severity, sleep and circadian rhythms, patient-reported symptoms, and data regarding biopsychosocial and clinical factors are collected. RESULTS:Results are pending study completion. DISCUSSION:We aim to target sleep and circadian rhythm disturbances, mitigate ICU delirium, and reduce cognitive decline associated with ADRD. If hypotheses are supported, this combination of low-cost, nonpharmacological interventions could be integrated into standard care to accelerate cognitive recovery during hospitalization.

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.

OBJECTIVE:To quantitate hypoxemia severity. METHODS:We developed the Weighted Hypoxemia Index to be adapted to different clinical settings by applying 5 steps to the oxygen saturation curve: (1) Identify desaturation/resaturation event [Formula: see text] by setting the upper threshold; (2) Exclude events as artifact by setting a lower threshold; (3) Calculate weighted area for each [Formula: see text] as [Formula: see text]; (4) Calculate a normalization factor [Formula: see text] for each subject; (5) Calculate the Weighted Hypoxemia Index as the summation of all weighted areas multiplied by [Formula: see text]. We assessed the Weighted Hypoxemia Index predictive value for all-cause mortality and cardiovascular mortality using the Sleep Heart Health Study (enrollment 1995-1998, 11.1 years mean follow-up). RESULTS:We set varying upper thresholds at 92%, 90%, 88%, and 86%, a lower threshold of 50%, calculated area under the curve and area above the curve, with and without a linear weighted factor (duration of each event [Formula: see text]), and used the same normalization factor of total sleep time <90% divided by total sleep time. After excluding subjects with missing data, we analyzed 4,509 participants (Alive: N = 3,769; All-cause mortality: N = 1,071; cardiovascular mortality: N = 330). Since the Weighted Hypoxemia Index-Area Under the Curve set at upper threshold of 90% (WHI-AUC90) had the best results in predicting all-cause mortality, we then compared it to the Apnea-Hypopnea Index and Total Sleep Time <90%. WHI-AUC90 showed statistical significance across quintiles for all-cause mortality, but not cardiovascular mortality, in adjusted Cox regression models. CONCLUSION:The Weighted Hypoxemia Index offers a versatile and clinically relevant method for quantifying hypoxemia severity, with potential applications to evaluate mechanisms and outcomes across various patient populations.

BackgroundOur understanding of sleep during early stroke care and its impact on rehabilitation outcomes remains limited. The objectives of this work were to (1) evaluate multidimensional sleep health and disruptions during acute inpatient rehabilitation for individuals with stroke, and (2) explore the relationship between sleep health/disruptions and functional recovery.MethodsData from 103 individuals with stroke were analyzed during acute inpatient rehabilitation. Sleep health/disruptions were assessed via patient reports, actigraphy, and biometric sensors. Functional outcomes were measured at admission and discharge. Generalized Linear Models (GLMs) were used to describe changes in sleep health over time, and multivariate regressions analyzed sleep disruptions and sleep-related predictors of functional recovery.ResultsOver inpatient stays, sleep improved with a 23% reduction in wake after sleep onset and 15% fewer multiple overnight disruptions. GLMs revealed that improved sleep quality was associated with reduced overnight activity and increased heart rate over time. Poor initial sleep quality and cognitive status were associated with more overnight disruptions. Lastly, minimal associations were found between sleep health and functional recovery.ConclusionsSleep health during inpatient stroke rehabilitation is generally poor, though improves over time. Sleep is affected by neurological recovery and hospital environment. Overnight activity and autonomic biomarkers were associated with perceived sleep health, and both physiological and environmental factors triggered disruptions. The association between functional recovery and indirect indicators of sleep health requires further investigation. These findings reveal new insights about inpatient sleep which can inform early, targeted sleep interventions to optimize post-stroke outcomes.SIESTA, ClinicalTrials.gov (NCT04254484).

BACKGROUND:Individual health behaviors are associated with pregnancy outcomes, but their joint effects are rarely considered and their associations with health beyond pregnancy are uncertain. We aimed to examine associations between combinations of first trimester health behaviors with adverse pregnancy outcomes (APOs) and blood pressure 2-7 years after delivery, and to estimate the proportion of associations with later blood pressure that were mediated by APOs. METHODS:Participants in the nuMoM2b and follow-up Heart Health Study prospective cohort were included. Physical activity, diet, sleep duration, and smoking were scored using the Life's Essential 8 framework. APOs were prospectively abstracted from medical records and included hypertensive disorders of pregnancy, preterm birth, gestational diabetes, small-for-gestational-age birth, or stillbirth. Latent profiles of health behaviors were constructed with structural equation modelling. Models were built using first trimester cardiovascular health scores on a scale of 0-100 for each of the four health behaviors. Risk of APOs and incident hypertension, and differences in continuous blood pressure 2-7 years after delivery based on behavioral profiles were assessed with Poisson or linear regression. Mediation analysis examined the proportion of associations between behavioral profiles and blood pressure mediated by APOs. RESULTS:Among 8,700 nulliparas, four behavioral profiles were identified: Healthiest Behaviors (36%), Healthy Activity/Sleep with Poor Diet/Smoking (21%), Healthy Sleep Only (32%), and Least Healthy Behaviors (11%). Forty-nine percent (4,497) returned for blood pressure assessment 2-7 years after delivery. Adjusted risk of APOs was 12-23% higher across the less healthy behavioral profiles compared to the Healthiest Behaviors profile. Further, adjusted systolic and diastolic blood pressures were 0.86 and 1.04 mmHg higher, respectively, 2-7 years after delivery in those with less healthy behavioral patterns compared to the Healthiest Behaviors profile. Eleven percent of the association between behavioral profiles and diastolic blood pressure was mediated by APOs. Rates of incident hypertension were not significantly different across behavioral profiles. CONCLUSIONS:Less healthy combined health behavior profiles in early pregnancy were associated with APOs and higher blood pressure 2-7 years after delivery. The observed associations with later blood pressure were predominately direct effects, with limited mediation through APOs.

OBJECTIVES:We performed a multidimensional analysis of mood, cognition, sleep and circadian rhythms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC) with the objective of characterizing the phenotype of PASC fatigue. METHODS:We recruited adult patients from a Neuro-COVID-19 Clinic with persistence of disabling symptoms beyond 6 weeks from acute infection. Self-reported symptoms were assessed with Patient-Reported Outcomes Measurement Information System instruments. We evaluated cognitive performance using NIH Toolbox measures and assessed sleep and rest-activity rhythms by 7 days of wrist actigraphy. We performed level 2 polysomnography in a subset of 20 participants. RESULTS:We studied 58 participants: 83% White, 59% female and 91% not hospitalized for COVID-19. Fatigue severity was significantly correlated with worse self-reported cognitive abilities but not with objectively measured cognitive performance and with greater depression symptoms, several rest-activity rhythm and light exposure disruption measures, and greater actigraphy measured sleep time and time in bed. A multivariable model found significant, independent associations between fatigue severity and subjective cognitive abilities, depression symptoms, and rest-activity rhythm disruption. CONCLUSIONS:Long total sleep times, disruption of light exposure and circadian rest-activity patterns, depression and subjective cognitive impairment are associated with PASC fatigue. Behaviorally influenced sleep and circadian abnormalities may exacerbate fatigue and be targets for therapeutic interventions.

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).