Oxytocin and women's health in midlife.

Menopause marks the cessation of fertility and the transition to post-reproductive years. Nearly 1M US women experience menopause annually, but despite the significant impact it has on their physical and mental health, menopause has been insufficiently studied. Oxytocin is a neurohormone that regulates emotionality, social behaviors, and fundamental physiological systems. Localization of oxytocin receptors in the brain, reproductive tissues, bone, and heart support their role in mental health and potentially sleep, along with reproductive and cardiovascular functions. While experimental data linking oxytocin to behavior and physiology in animals are largely consistent, human data are correlative and inconclusive. As women transition into menopause, oxytocin levels decrease while their susceptibility to mood disorders, poor sleep, osteoporosis, and cardiovascular diseases increases. These concurrent changes highlight oxytocin as a potential influence on the health and mood of women along their reproductive lifespan. Here we summarize experimental rodent studies that link oxytocin to reproductive aging and metabolic health and highlight the inconclusive findings in studies of women. Most human studies relied on a single oxytocin assessment in plasma or on intranasal oxytocin administration. The pulsatile release and short half-life of plasma oxytocin limits the validity of these methods. We discuss the need for oxytocin assessments in stable bio-samples, such as urine, and to use valid assays for assessment of associations between changing oxytocin levels and well-being across the reproductive lifespan. This work has the potential to guide therapeutic strategies that will one day alleviate adverse health outcomes for many women.

Association between sleep-disordered breathing and post-stroke fatigue in patients with ischemic stroke.

OBJECTIVES: Post-stroke fatigue (PSF) is common and often disabling. Sleep-disordered breathing (SDB) is highly prevalent among stroke survivors and can cause fatigue. We explored the relationship between SDB and PSF over time. MATERIALS AND METHODS: Ischemic stroke (IS) patients within the BASIC project were offered SDB screening with a well-validated cardiopulmonary sleep apnea test at 0, 3-, 6-, and 12-months post-stroke. The primary exposure was the respiratory event index (REI; sum of apneas plus hypopneas per hour). The primary outcome was PSF, measured by the SF-36 vitality scale. Associations between REI and PSF were evaluated using linear regression including time-by-REI interactions, allowing the effect of REI to vary over time. RESULTS: Of the 411 IS patients who completed at least one outcome interview, 44 % were female, 61 % Mexican American (MA), 26 % non-Hispanic white, with a mean age of 64 (SD 10). Averaged across timepoints, REI was not associated with PSF. In a time-varying model, higher REI was associated with greater PSF at 3-months (ß = 1.75, CI = 0.08, 3.43), but not at 6- or 12-months. Across timepoints, female sex, depressive symptoms, and comorbidity burden were associated with greater PSF, whereas MA ethnicity was associated with less PSF. CONCLUSIONS: Higher REI was associated with modestly greater PSF in the early post-stroke period, but no association was observed at 6 months and beyond. SDB may be a modest modifiable risk factor for early PSF, but its treatment is unlikely to have a substantial impact on long-term PSF. MA ethnicity seems to be protective against PSF.

Patterns of Sleep Duration and Metabolic Biomarkers Across the Menstrual Cycle.

CONTEXT: Along the menstrual cycle, associations between inconsistent sleep duration and levels of metabolic biomarkers are uncertain and could involve fluctuations in estrogen concentrations. OBJECTIVE: To examine associations between patterns of sleep duration and metabolic biomarkers across two menstrual cycles within a cohort of premenopausal women. METHODS: The BioCycle Study was conducted in New York between 2005-2007, enrolling 259 premenopausal women over two menstrual cycles. This micro-longitudinal cohort study involved intensive data collection including daily sleep diaries and biomarker assessments of leptin, insulin, and glucose at 16 key points timed to menstrual cycle phases. We considered dynamic sleep duration, as hours slept one night or as mean hours slept during the two nights prior to each biomarker assessment. Variability in habitual sleep duration, i.e., reported daily sleep duration, summarized across both menstrual cycles. Variation in habitual sleep duration was computed using L-moments, a robust version of dispersion, skewness, and kurtosis. To examine associations between patterns of sleep duration and metabolic biomarkers, we fitted a series of linear mixed models with random intercepts and inverse probability weighting. These models were adjusted for potential demographic, lifestyle, health confounders, and menstrual cycle phase. RESULTS: Sleep duration one night or two nights prior to clinic visits were not associated with metabolic biomarker measures we assessed. However, overall variability (dispersion) in habitual sleep duration was associated with lower mean insulin HOMA-IR levels, but not glucose. Moreover, extreme short or long bouts of sleep duration was associated with higher mean levels of leptin, insulin, and HOMA-IR. CONCLUSIONS: These data suggest that variation in habitual sleep duration along the menstrual cycle may be associated with metabolic function.

Neighborhood Disadvantage, Quality of Life, and Symptom Burden in Children with Mild Sleep-disordered Breathing.

Rationale: Neighborhood disadvantage (ND) has been associated with sleep-disordered breathing (SDB) in children. However, the association between ND and SDB symptom burden and quality of life (QOL) has not yet been studied.Objectives: To evaluate associations between ND with SDB symptom burden and QOL.Methods: Cross-sectional analyses were performed on 453 children, ages 3-12.9 years, with mild SDB (habitual snoring and apnea-hypopnea index < 3/h) enrolled in the PATS (Pediatric Adenotonsillectomy Trial for Snoring) multicenter study. The primary exposure, neighborhood disadvantage, was characterized by the Child Opportunity Index (COI) (range, 0-100), in which lower values (specifically COI ⩽ 40) signify less advantageous neighborhoods. The primary outcomes were QOL assessed by the obstructive sleep apnea (OSA)-18 questionnaire (range, 18-126) and SDB symptom burden assessed by the Pediatric Sleep Questionnaire-Sleep-related Breathing Disorder (PSQ-SRBD) scale (range, 0-1). The primary model was adjusted for age, sex, race, ethnicity, maternal education, recruitment site, and season. In addition, we explored the role of body mass index (BMI) percentile, environmental tobacco smoke (ETS), and asthma in these associations.Results: The sample included 453 children (16% Hispanic, 26% Black or African American, 52% White, and 6% other). COI mean (standard deviation [SD]) was 50.3 (29.4), and 37% (n = 169) of participants lived in disadvantaged neighborhoods. Poor SDB-related QOL (OSA-18 ⩾ 60) and high symptom burden (PSQ-SRBD ⩾ 0.33) were found in 30% (n = 134) and 75% (n = 341) of participants, respectively. In adjusted models, a COI increase by 1 SD (i.e., more advantageous neighborhood) was associated with an improvement in OSA-18 score by 2.5 points (95% confidence interval [CI], -4.34 to -0.62) and in PSQ-SRBD score by 0.03 points (95% CI, -0.05 to -0.01). These associations remained significant after adjusting for BMI percentile, ETS, or asthma; however, associations between COI and SDB-related QOL attenuated by 23% and 10% after adjusting for ETS or asthma, respectively.Conclusions: Neighborhood disadvantage was associated with poorer SDB-related QOL and greater SDB symptoms. Associations were partially attenuated after considering the effects of ETS or asthma. The findings support efforts to reduce ETS and neighborhood-level asthma-related risk factors and identify other neighborhood-level factors that contribute to SDB symptom burden as strategies to address sleep-health disparities.Clinical trial registered with www.clinicaltrials.gov (NCT02562040).

Clinical Characteristics of Primary Snoring vs Mild Obstructive Sleep Apnea in Children: Analysis of the Pediatric Adenotonsillectomy for Snoring (PATS) Randomized Clinical Trial.

Importance: It is unknown whether children with primary snoring and children with mild obstructive sleep apnea (OSA) represent populations with substantially different clinical characteristics. Nonetheless, an obstructive apnea-hypopnea index (AHI) of 1 or greater is often used to define OSA and plan for adenotonsillectomy (AT). Objective: To assess whether a combination of clinical characteristics differentiates children with primary snoring from children with mild OSA. Design, Setting, and Participants: Baseline data from the Pediatric Adenotonsillectomy Trial for Snoring (PATS) study, a multicenter, single-blind, randomized clinical trial conducted at 6 academic sleep centers from June 2016 to January 2021, were analyzed. Children aged 3.0 to 12.9 years with polysomnography-diagnosed (AHI <3) mild obstructive sleep-disordered breathing who were considered candidates for AT were included. Data analysis was performed from July 2022 to October 2023. Main Outcomes and Measures: Logistic regression models were fitted to identify which demographic, clinical, and caregiver reports distinguished children with primary snoring (AHI <1; 311 patients [67.8%]) from children with mild OSA (AHI 1-3; 148 patients [32.2%]). Results: A total of 459 children were included. The median (IQR) age was 6.0 (4.0-7.5) years, 230 (50.1%) were female, and 88 (19.2%) had obesity. A total of 121 (26.4%) were Black, 75 (16.4%) were Hispanic, 236 (51.5%) were White, and 26 (5.7%) were other race and ethnicity. Black race (odds ratio [OR], 2.08; 95% CI, 1.32-3.30), obesity (OR, 1.80; 95% CI, 1.12-2.91), and high urinary cotinine levels (>5 µg/L) (OR, 1.88; 95% CI, 1.15-3.06) were associated with greater odds of mild OSA rather than primary snoring. Other demographic characteristics, clinical examination findings, and questionnaire reports did not distinguish between primary snoring and mild OSA. A weighted combination of the statistically significant clinical predictors had limited ability to differentiate children with mild OSA from children with primary snoring. Conclusions and Relevance: In this analysis of baseline data from the PATS randomized clinical trial, primary snoring and mild OSA were difficult to distinguish without polysomnography. Mild OSA vs snoring alone did not identify a clinical group of children who may stand to benefit from AT for obstructive sleep-disordered breathing. Trial Registration: ClinicalTrials.gov Identifier: NCT02562040.

Novel metrics of sleep-disordered breathing are associated with outcome after ischemic stroke.

OBJECTIVE/BACKGROUND: Standard measures of sleep-disordered breathing (SDB) that rely on count data may not sufficiently capture SDB severity or reflect downstream consequences of SDB. We hypothesized that novel metrics derived from pulse rate, oxygen saturation, and nasal pressure would be associated with stroke outcomes. PATIENTS/METHODS: Shortly after ischemic stroke, participants in a population-based study were offered ApneaLink Plus testing. Signal analysis was used to generate 166 metrics from the nasal pressure cannula and finger probe, categorized as: autonomic (based on pulse rate variability), oximetry-derived, nasal pressure-derived, and mixed oxygen and nasal pressure-derived measures. Three-month outcome assessments included functional and cognitive outcomes and stroke recurrence. Tobit regression and Cox proportional hazards models were used to examine associations between each sleep apnea metric and the three outcomes, unadjusted and adjusted for multiple potential confounders. Models were adjusted for multiple comparisons. RESULTS: Of the 530 participants, the median age was 65 (IQR: 57, 73), 49 % were female, and 64 % were Mexican American. Without covariate adjustment, 23 of 166 variables were associated with functional outcome, 43 were associated with cognitive outcome, and 1 was associated with stroke recurrence. After adjustment, 7 mixed, oximetry, or nasal pressure-based metrics and 1 autonomic metric were associated with functional outcome, but none was associated with cognitive outcome or stroke recurrence. CONCLUSIONS: Many novel metrics of SDB were associated with important stroke outcomes, and 8 novel metrics were associated with functional outcome in adjusted models. This raises hypotheses about pathways by which SDB may negatively impact stroke outcomes.

Adenotonsillectomy for Snoring and Mild Sleep Apnea in Children: A Randomized Clinical Trial.

Importance: The utility of adenotonsillectomy in children who have habitual snoring without frequent obstructive breathing events (mild sleep-disordered breathing [SDB]) is unknown. Objectives: To evaluate early adenotonsillectomy compared with watchful waiting and supportive care (watchful waiting) on neurodevelopmental, behavioral, health, and polysomnographic outcomes in children with mild SDB. Design, Setting, and Participants: Randomized clinical trial enrolling 459 children aged 3 to 12.9 years with snoring and an obstructive apnea-hypopnea index (AHI) less than 3 enrolled at 7 US academic sleep centers from June 29, 2016, to February 1, 2021, and followed up for 12 months. Intervention: Participants were randomized 1:1 to either early adenotonsillectomy (n = 231) or watchful waiting (n = 228). Main Outcomes and Measures: The 2 primary outcomes were changes from baseline to 12 months for caregiver-reported Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC) T score, a measure of executive function; and a computerized test of attention, the Go/No-go (GNG) test d-prime signal detection score, reflecting the probability of response to target vs nontarget stimuli. Twenty-two secondary outcomes included 12-month changes in neurodevelopmental, behavioral, quality of life, sleep, and health outcomes. Results: Of the 458 participants in the analyzed sample (231 adenotonsillectomy and 237 watchful waiting; mean age, 6.1 years; 230 female [50%]; 123 Black/African American [26.9%]; 75 Hispanic [16.3%]; median AHI, 0.5 [IQR, 0.2-1.1]), 394 children (86%) completed 12-month follow-up visits. There were no statistically significant differences in change from baseline between the 2 groups in executive function (BRIEF GEC T-scores: -3.1 for adenotonsillectomy vs -1.9 for watchful waiting; difference, -0.96 [95% CI, -2.66 to 0.74]) or attention (GNG d-prime scores: 0.2 for adenotonsillectomy vs 0.1 for watchful waiting; difference, 0.05 [95% CI, -0.18 to 0.27]) at 12 months. Behavioral problems, sleepiness, symptoms, and quality of life each improved more with adenotonsillectomy than with watchful waiting. Adenotonsillectomy was associated with a greater 12-month decline in systolic and diastolic blood pressure percentile levels (difference in changes, -9.02 [97% CI, -15.49 to -2.54] and -6.52 [97% CI, -11.59 to -1.45], respectively) and less progression of the AHI to greater than 3 events/h (1.3% of children in the adenotonsillectomy group compared with 13.2% in the watchful waiting group; difference, -11.2% [97% CI, -17.5% to -4.9%]). Six children (2.7%) experienced a serious adverse event associated with adenotonsillectomy. Conclusions: In children with mild SDB, adenotonsillectomy, compared with watchful waiting, did not significantly improve executive function or attention at 12 months. However, children with adenotonsillectomy had improved secondary outcomes, including behavior, symptoms, and quality of life and decreased blood pressure, at 12-month follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT02562040.

Disparities in sleep-wake patterns by labor force status: Population-based findings.

Sleep disturbances have been associated with unemployment, but variation in sleep-wake patterns by labor force status has rarely been examined. With a population-based sample, we investigated differences in sleep-wake patterns by labor force status (employed, unemployed, and not-in-the-labor-force) and potential disparities by sociodemographic variables. The analysis included 130,602 adults aged 25-60 y, who participated in the American Time Use Survey between 2003 and 2019. Individual sleep-wake pattern was extracted from time use logs in a strict 24-h period (04:00 h-03:59 h). Functional nonparametric regression models based on dimensionality reduction and neighborhood matching were applied to model the relationship between sleep-wake patterns and labor force status. Specifically, we predicted changes in intra-person sleep-wake patterns under hypothetical changes of labor force status from employed to unemployed or not-in-the-labor-force. We then studied moderations of this association by gender, race/ethnicity and educational attainment. In comparison to the employed state, unemployed and not-in-the-labor-force states were predicted to have later wake-times, later bedtimes, and higher tendency for taking midday naps. Changes in labor force status led to more apparent shifts in wake-times than in bedtimes. Additionally, sleep schedules of Hispanics and those with higher education level were more vulnerable to the change of labor force status from employed to unemployed.

Longitudinal Assessment of Sleep Apnea in the Year After Stroke in a Population-Based Study.

BACKGROUND: The aim of this study was to characterize change in sleep-disordered breathing severity in the year following stroke, overall, and by ethnicity, within the population-based Brain Attack Surveillance in Corpus Christi Project. METHODS: First-ever ischemic strokes (n=414) were ascertained by active and passive surveillance and validated by stroke-trained physicians. Patients with stroke were invited to participate in portable sleep apnea testing (ApneaLink Plus) at baseline and 3, 6, and 12 months poststroke. Sleep-disordered breathing severity was assessed by the respiratory event index (apneas and hypopneas/hour of recording). The component obstructive apnea index and central apnea index were also assessed. Time and ethnicity effects on outcomes, as well as ethnic differences in time effects, were analyzed using generalized estimating equations with multivariable adjustment for confounding factors. RESULTS: Mean age (n=414) was 63.9 years (SD=10.9); 68.4% were Mexican American. Baseline mean respiratory event index, obstructive apnea index, and central apnea index were 21.3 (SD=16.6), 8.6 (SD=11.5), and 1.5 (SD=3.2), respectively. There was no time effect on respiratory event index (P=0.35) but obstructive apnea index increased over time (P<0.01). Averaged over follow-up, respiratory event index and obstructive apnea index were significantly higher in Mexican American than non-Hispanic White persons. No ethnic difference in the time effect was found for either outcome. For central apnea index, there was an ethnicity-time interaction (P=0.01) such that central apnea index increased in non-Hispanic White but did not change in Mexican American persons. CONCLUSIONS: Sleep-disordered breathing severity was significant and stable for most individuals in the year after stroke. These results do not confirm previous reports of diminishing sleep-disordered breathing severity over time after stroke and would support early assessment and treatment where indicated.

Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains.

BACKGROUND: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. OBJECTIVE: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. METHODS: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). RESULTS: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) (ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) (ps ⩽ 0.011). CONCLUSIONS: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02544373 (https://clinicaltrials.gov/ct2/show/NCT02544373).

Associations of actigraphy measures of sleep duration and continuity with executive function, vigilance, and fine motor control in children with snoring and mild sleep-disordered breathing.

STUDY OBJECTIVES: Children with snoring and mild sleep-disordered breathing may be at increased risk for neurocognitive deficits despite few obstructive events. We hypothesized that actigraphy-based sleep duration and continuity associate with neurobehavioral functioning and explored whether these associations vary by demographic and socioeconomic factors. METHODS: 298 children enrolled in the Pediatric Adenotonsillectomy Trial, ages 3 to 12.9 years, 47.3% from racial or ethnic minority groups, with habitual snoring and an apnea-hypopnea index < 3 were studied with actigraphy (mean 7.5 ± 1.4 days) and completed a computerized vigilance task (Go-No-Go) and a test of fine motor control (9-Hole Pegboard). Caregivers completed the Behavior Rating Inventory of Executive Function. Regression analyses evaluated associations between sleep exposures (24-hour and nocturnal sleep duration, sleep fragmentation index, sleep efficiency) with the Behavior Rating Inventory of Executive Function Global Executive Composite index, pegboard completion time (fine motor control), and vigilance (d prime on the Go-No-Go), adjusting for demographic factors and study design measures. RESULTS: Longer sleep duration, higher sleep efficiency, and lower sleep fragmentation were associated with better executive function; each additional hour of sleep over 24 hours associated with more than a 3-point improvement in executive function (P = .002). Longer nocturnal sleep (P = .02) and less sleep fragmentation (P = .001) were associated with better fine motor control. Stronger associations were observed for boys and children less than 6 years old. CONCLUSIONS: Sleep quantity and continuity are associated with neurocognitive functioning in children with mild sleep-disordered breathing, supporting efforts to target these sleep health parameters as part of interventions for reducing neurobehavioral morbidity. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Pediatric Adenotonsillectomy for Snoring (PATS); URL: https://clinicaltrials.gov/ct2/show/NCT02562040; Identifier: NCT02562040. CITATION: Robinson KA, Wei Z, Radcliffe J, et al. Associations of actigraphy measures of sleep duration and continuity with executive function, vigilance, and fine motor control in children with snoring and mild sleep-disordered breathing. J Clin Sleep Med. 2023;19(9):1595-1603.

Positive airway pressure treatment for sleep-disordered breathing is rare during the first year after stroke: The BASIC project.

OBJECTIVE/BACKGROUND: Sleep-disordered breathing (SDB) is very common after ischemic stroke, and its treatment may have a positive impact on recovery from stroke and on secondary stroke prevention. This study sought to determine the prevalence of positive airway pressure (PAP) use after stroke. PATIENTS/METHODS: Participants in the Brain Attack Surveillance in Corpus Christi (BASIC) project underwent a home sleep apnea test shortly after ischemic stroke. Demographics and co-morbidities were ascertained from the medical record. Self-reported PAP use (present vs absent) was assessed at 3, 6, and 12 months after stroke. Fisher exact tests and t-tests were used to compare PAP users versus non-users. RESULTS: Of 328 participants who were found to have SDB after stroke, only 20 (6.1%) indicated using PAP at any point during the 12-month follow up period. High pre-stroke sleep apnea risk based on Berlin Questionnaire score, neck circumference, and co-morbid atrial fibrillation were associated with any self-reported PAP use; race/ethnicity, insurance status and other demographic variables were not associated with PAP use. CONCLUSIONS: Only a small proportion of individuals with ischemic stroke and SDB received treatment with PAP during the initial year after stroke among participants in this population-based cohort study in Nueces County, Texas. Closing the substantial treatment gap for SDB after stroke might improve sleepiness and neurologic recovery.

Preoperative Predictors of Severe Respiratory Events After Tonsillectomy: Consideration for Pediatric Intensive Care Admission.

OBJECTIVE: Few data are available to guide postadenotonsillectomy (AT) pediatric intensive care (PICU) admission. The aim of this study of children with a preoperative polysomnogram (PSG) was to assess whether preoperative information may predict severe respiratory events (SRE) after AT. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary center. METHODS: Children aged 6 months to 17 years who underwent AT with preoperative polysomnography (2012-2018) were identified by billing codes. Data were extracted from medical records. SRE were defined as any 1 or more of desaturations <80% requiring intervention; newly initiated positive airway pressure; postoperative intubation; pneumonia/pneumonitis; respiratory code, cardiac arrest, or death. We hypothesized that SRE would be associated with age <24 months, major medical comorbidity, obesity (>95th percentile), apnea-hypopnea index (AHI) ≥ 30, and O2 nadir <70% on PSG. Analysis was performed with multivariable logistic regression. RESULTS: Of 1774 subjects, 28 (1.7%) experienced SRE. Compared to those without, children with SRE were on average younger (3 vs 5 years, p < .01) with a greater probability of medical comorbidities (59% vs 18%, p < .001). After adjustment for sex, black race, obesity, and age <24 months, children with major medical comorbidity were more likely than other children to have SRE (odds ratio [OR]: 14.2; 95% confidence interval [CI]: [5.7, 35.2]), as were children with AHI ≥ 30 (OR: 7.7 [3.0, 19.9]), or O2 nadir <70% (OR 6.1 [2.1, 17.9]). Age, obesity, sex, and black race did not independently predict SRE. CONCLUSION: PICU admission may be most prudent for children with complex medical co-morbidities, high AHI (>30), and/or low O2 nadir (<70%).

Variability in Sleep Duration and Biomarkers of Cardiovascular Disease Across the Menstrual Cycle.

Variability in sleep duration and cardiovascular health have been infrequently investigated, particularly among reproductive-age women. We examined these associations across the menstrual cycle among a cohort of 250 healthy premenopausal women, aged 18-44 years. The BioCycle study (New York, 2005-2007) collected cardiovascular biomarkers (serum high- and low-density lipoprotein (HDL, LDL), total cholesterol, triglycerides, and C-reactive protein (CRP)) at key time points along the menstrual cycle (follicular, ovulatory, and luteal phases). Women also recorded sleep duration in daily diaries. From these data, we computed L-moments, robust versions of location, dispersion, skewness, and kurtosis. We fitted linear mixed models with random intercepts and inverse probability weighting to estimate associations between sleep variability and cardiovascular biomarkers, accounting for demographic, lifestyle, health, and reproductive factors. Sleep dispersion (any deviation from mean duration) was associated with lower mean LDL for nonshift workers and non-White women. Skewed sleep duration was associated with higher mean CRP and lower mean total cholesterol. Sleep durations with extreme short and long bouts (kurtosis) were associated with a lower mean HDL, but not mean CRP, LDL, or triglycerides. Sleep duration modified associations between sleep dispersion and LDL, HDL, and total cholesterol. Even in young and healthy women, sleep duration variability could influence cardiovascular health.

Sleep duration and timing are prospectively linked with insulin resistance during late adolescence.

OBJECTIVE: The aim of this study was to evaluate whether short sleep duration or later sleep timing is a risk factor for insulin resistance (IR) in late adolescence. METHODS: Mexico City adolescents enrolled in a longitudinal birth cohort (ELEMENT) took part in two study visits during peri-puberty that occurred approximately 2 years apart. IR was assessed with serum glucose and insulin. Four groups were defined using puberty-specific cut points: no IR over the follow-up period, transition from normal to IR, transition from IR to normal, and IR at both time points. Baseline sleep assessments were measured with 7-day wrist actigraphy. Multinomial logistic regression models were used to evaluate associations between sleep duration and timing with homeostatic model assessment of insulin resistance categories, adjusting for age, sex, and baseline pubertal status. RESULTS: Adolescents who were ≥ 1 hour below the sleep duration recommendations-for-age were 2.74 times more likely to develop IR (95% CI: 1.0-7.4). Similarly, adolescents who were in the latest category of sleep midpoint (>4:33 a.m.) were more likely than those with earliest midpoints (1 a.m.-3 a.m.) to develop IR (odds ratio = 2.63, 95% CI: 1.0-6.7). Changes in adiposity over follow-up did not mediate sleep and IR. CONCLUSIONS: Insufficient sleep duration and late sleep timing were associated with development of IR over a 2-year period in late adolescence.

Mental and physical health pathways linking insomnia symptoms to cognitive performance 14 years later.

STUDY OBJECTIVES: Insomnia may be a modifiable risk factor for later-life cognitive impairment. We investigated: (1) which insomnia symptoms are associated with subsequent cognitive functioning across domains; (2) whether insomnia-cognition associations are mediated by mental and physical health; and (3) whether these associations are modified by gender. METHODS: Participants included 2595 adults ages 51-88 at baseline (Mage=64.00 ± 6.66, 64.5% women) in the Health and Retirement Study. The frequency of insomnia symptoms (difficulty initiating sleep, night time awakenings, early awakenings, and feeling unrested upon awakening) at baseline (2002) were quantified using a modified Jenkins Sleep Questionnaire. Cognition was assessed in 2016 via the Harmonized Cognitive Assessment Protocol and operationalized with factor scores corresponding to five domains. Depressive symptoms and vascular conditions in 2014 were assessed via self-report. Structural equation models estimated total, indirect, and direct effects of insomnia symptoms on subsequent cognition through depressive symptoms and vascular diseases, controlling for baseline sociodemographic and global cognition. RESULTS: Frequent difficulty initiating sleep was associated with poorer episodic memory, executive function, language, visuoconstruction, and processing speed 14 years later (-0.06 ≤ ß ≤ -0.04; equivalent to 2.2-3.4 years of aging). Depressive symptoms explained 12.3%-19.5% of these associations and vascular disease explained 6.3%-14.6% of non-memory associations. No other insomnia symptoms were associated with cognition, and no associations were modified by gender. CONCLUSIONS: Difficulty initiating sleep in later life may predict future cognitive impairment through multiple pathways. Future research with longitudinal assessments of insomnia, insomnia treatments, and cognition is needed to evaluate insomnia as a potential intervention target to optimize cognitive aging.

Racial and ethnic differences in sleep-disordered breathing and sleep duration among stroke patients.

OBJECTIVE: We sought to characterize racial and ethnic differences in pre- and post-stroke sleep-disordered breathing (SDB) and pre-stroke sleep duration. METHODS: Within the Brain Attack Surveillance in Corpus Christi cohort of patients with ischemic stroke (8/26/2010-1/31/2020), pre-stroke SDB risk was assessed retrospectively using the Berlin Questionnaire. Post-stroke SDB was defined by prospective collection of the respiratory event index (REI) using the ApneaLink Plus performed shortly after stroke. Pre-stroke sleep duration was self-reported. We used separate regression models to evaluate the association between race/ethnicity and each outcome (pre-stroke SDB, post-stroke SDB, and pre-stroke sleep duration), without and with adjustment for potential confounders. RESULTS: There was no difference in pre-stroke risk of SDB between Black and non-Hispanic white (NHW) participants (odds ratio (OR) 1.07, 95% CI 0.77-1.49), whereas MA (Mexican American), compared to NHW, participants had a higher risk of SDB before adjusting for demographic and clinical variables (OR 1.26, 95% CI 1.08-1.47). Post-stroke SDB risk was higher in MA (estimate 1.16, 95% CI 1.06-1.28) but lower in Black (estimate 0.79, 95% CI 0.65-0.96) compared to NHW participants; although, only the ethnic difference remained after adjustment. MA and Black participants had shorter sleep duration than NHW participants (OR 0.83, 95% CI 0.72-0.96 for MA; OR 0.67, 95% CI 0.49-0.91 for Black participants) before but not after adjustment. CONCLUSIONS: Racial/ethnic differences appear likely to exist in pre- and post-stroke SDB and pre-stroke sleep duration. Such differences might contribute to racial/ethnic disparities in stroke incidence and outcomes.

Ethnic differences exist in sleepiness 3 Months after ischemic stroke.

OBJECTIVE/BACKGROUND: To examine the association between ethnicity and 90-day post-stroke subjective sleepiness, an important determinant of quality of life, as measured by the Epworth Sleepiness Scale (ESS), among ischemic stroke survivors. PATIENTS/METHODS: Mexican American (MA) and non-Hispanic white (NHW) recent ischemic stroke patients were identified from the population-based Brain Attack Surveillance in Corpus Christi Project (2010-2016). Subjects completed a baseline interview and 90-day outcome assessment that included the ESS. Excessive daytime sleepiness was defined as an ESS >10. Tobit regression models were used to assess associations between ethnicity and ESS unadjusted and adjusted for multiple potential confounders. RESULTS: Among 1,181 (62.5% MA) subjects, mean ESS at 90 days was 8.9 (SD 6.0) among MA and 7.4 (SD 4.9) among NHW subjects: 1.45 (95% CI: 0.75, 2.15) points higher among MA than NHW subjects. After adjustment, mean ESS at 90 days was 1.16 (95% CI: 0.38, 1.94) points higher among MAs than NHWs. The prevalence of excessive daytime sleepiness was 39% among MA and 30% among NHW subjects (p = 0.0013). CONCLUSIONS: Ninety days after stroke, sleepiness is worse in MAs compared to NHWs, even after accounting for potential confounding variables. Further studies should address ways to reduce this disparity.

Effects of a Sleep Health Education Program for Children and Parents on Child Sleep Duration and Difficulties: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Preschool-aged children often lack sufficient sleep and experience sleep difficulties. A consistent bedtime routine, falling asleep alone, and other sleep practices reduce difficulties and increase sleep duration. Objective: To evaluate the effects of a preschool-based sleep health literacy program on children's sleep duration and difficulties and on parent sleep knowledge, attitudes, self-efficacy, and beliefs 9 and 12 months after the program. Design, Setting, and Participants: This stepped-wedge cluster randomized clinical trial was implemented across the 2018-2019 school year. Head Start preschool personnel delivered interventions and collected outcomes data at baseline and 4 follow-ups. Seven Head Start agencies across New York State were randomized to implement interventions in either fall 2018 or winter and spring 2019. Outcomes were ascertained at 9- and 12-month follow-up. From March 19 through September 28, 2018, Head Start staff recruited (a) English- or Spanish-speaking parents (b) of children 3 years of age on or about September 2018 (c) who planned to remain at the site through the school year. Altogether, 519 parent-child (aged 3 years) dyads completed baseline and (any) follow-up data. Interventions: A 2-week classroom curriculum for children, a 1-hour parent workshop, and 1-on-1 parent discussions at home or school. Main Outcomes and Measures: Outcomes were the pre- vs postintervention differences measured at baseline and 9-month follow-up for parent-reported child school-night sleep duration per sleep logs, mild or moderate sleep difficulties per a validated questionnaire, and the total and domain scores for parent sleep knowledge, attitudes, self-efficacy, and beliefs. A modified intention-to-treat analysis excluding participants with only baseline data was used. Results: The mean (SD) age at enrollment of 519 children was 2.7 (0.1) years, 264 (50.9%) were girls, 196 (37.8%) lived in Spanish-speaking households, and 5 (0.9%) identified as Alaskan Native or American Indian, 17 (3.2%) as Asian American or Pacific Islander, 57 (10.8%) as Black, 199 (37.8%) as White, and 63 (12.0%) as other. Mean sleep durations increased nonsignificantly from baseline by 5.6 minutes (95% CI, -2.3 to 13.6 minutes; P = .17) at 9-month follow-up and by 6.8 minutes (95% CI, 0.2-13.7 minutes; P = .06) at 12-month follow-up. There was a slight improvement in parental knowledge (1.13 unit increase from baseline; 95% CI, 0.13-2.12 units), but no significant outcomes for parent sleep attitudes (0.16 unit increase from baseline; 95% CI, -0.46 to 0.77 units), self-efficacy (-0.13 unit decrease from baseline; 95% CI, -1.02 to 0.76 units) and beliefs (-0.20 unit decrease from baseline; 95% CI, -0.56 to 0.16 units). Intervention effects for child sleep difficulties were not significant (odds ratio, 1.13; 95% CI, 0.62-2.09). Fewer than 1 in 4 parents accurately perceived their child's sleep difficulty at 12 months. Conclusions and Relevance: The findings of this large pragmatic, stepped-wedge cluster randomized clinical trial, albeit largely negative, may have implications for the sustained impact, focus, and potential population-level effects of sleep education programs. Future research should evaluate the effects of more recurrent programming that emphasizes recognition of sleep problems and whether small increments of sleep across months and years in early childhood have meaningful effects. Trial Registration: ClinicalTrials.gov Identifier: NCT03556462.