Why the worsening at rest and worsening at night criteria for Restless Legs Syndrome are listed separately: review of the circadian literature on RLS and suggestions for future directions

The field of circadian research on Restless Legs Syndrome (RLS) and periodic limb movements (PLMs) is reviewed in general. RLS has five obligatory criteria for diagnosis: (1) an urge to move the legs often accompanied by uncomfortable leg sensations; (2) symptoms are worse at rest, i.e., lying or sitting; (3) there is a least partial and temporary relief of symptoms by activity, e.g., walking or stretching or bending the legs; (4) symptoms are worse later in the day or at night; and (5) mimics of RLS such as leg cramps and positional discomfort should be excluded by history and physical. In addition, RLS is frequently accompanied by PLMs, either periodic limb movements of sleep (PLMS) as determined by polysomnography or periodic limb movements while awake (PLMW) as determined by the suggested immobilization test (SIT). Since the criteria for RLS were based upon clinical experience only, an early question after the development of the criteria was whether criteria 2 and 4 were the same or different phenomena. In other words, were RLS patients worse at night only because they were lying down, and were RLS patients worse lying down only because it was night? Early circadian studies performed during recumbency at different times of the day suggest that the uncomfortable sensations, PLMS, and PLMW as well as voluntary movement in response to leg discomfort follow a similar circadian pattern with worsening at night independent of body position and independent of sleep timing or duration. Other studies demonstrated that RLS patients get worse when sitting or lying down independent of the time of day. These studies as a whole suggest that the worsening at rest and the worsening at night criteria for RLS are related but separate phenomena and that criteria 2 and 4 for RLS should be kept separate based upon the circadian studies, as had been the case previously based upon clinical grounds alone. To more fully prove the circadian rhythmicity of RLS, studies should be conducted to see if bright light shifts the signs and symptoms of RLS to a different circadian time in concert with circadian markers

A timely call to arms: COVID-19, the circadian clock, and critical care

We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on how knowledge of the circadian clock might be used to mitigate the disease expression and the clinical course of COVID-19

Racial/Ethnic Differences in Sleep Disturbances: The Multi-Ethnic Study of Atherosclerosis (MESA)

Objectives: There is limited research on racial/ethnic variation in sleep disturbances. This study aimed to quantify the distributions of objectively measured sleep disordered breathing (SDB), short sleep duration, poor sleep quality, and self-reported sleep disturbances (e.g., insomnia) across racial/ethnic groups. Design: Cross-sectional study. Setting: Six US communities. Participants: Racially/ethnically diverse men and women aged 54–93 y in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (n = 2,230). Interventions: N/A. Measurements and Results: Information from polysomnography-measured SDB, actigraphy-measured sleep duration and quality, and selfreported daytime sleepiness were obtained between 2010 and 2013. Overall, 15.0% of individuals had severe SDB (apnea-hypopnea index [AHI] ≥ 30); 30.9% short sleep duration (< 6 h); 6.5% poor sleep quality (sleep efficiency <85%); and 13.9% had daytime sleepiness. Compared with Whites, Blacks had higher odds of sleep apnea syndrome (AHI ≥ 5 plus sleepiness) (sex-, age-, and study site-adjusted odds ratio [OR] = 1.78, 95% confidence interval [CI]: 1.20, 2.63), short sleep (OR = 4.95, 95% CI: 3.56, 6.90), poor sleep quality (OR = 1.57, 95% CI: 1.00, 2.48), and daytime sleepiness (OR = 1.89, 95% CI: 1.38, 2.60). Hispanics and Chinese had higher odds of SDB and short sleep than Whites. Among nonobese individuals, Chinese had the highest odds of SDB compared to Whites. Only 7.4% to 16.2% of individuals with an AHI ≥ 15 reported a prior diagnosis of sleep apnea. Conclusions: Sleep disturbances are prevalent among middle-aged and older adults, and vary by race/ethnicity, sex, and obesity status. The high prevalence of sleep disturbances and undiagnosed sleep apnea among racial/ethnic minorities may contribute to health disparities. Keywords: apnea-hypopnea index, body mass index, daytime sleepiness, obesity, polysomnography, race/ethnicity, sleep disordered breathing, sleep disturbance, sleep duration, sleep qualit

Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep

Introduction: Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves. Aims: Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use. Methods: Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented. Results: Results showed that the sound stimulation increased both slow wave (p =.002) and sleep spindle activity (p Conclusions: We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future.Peer reviewe

Sex-Specific Prediction Models for Sleep Apnea From the Hispanic Community Health Study/Study of Latinos

OBJECTIVE: We developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects. METHODS: Cross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea-hypopnea index ≥ 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex × covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered. RESULTS: A total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea index ≥ 15 events per hour) was 6.1% in female subjects and 13.5% in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie, age, BMI, self-reported snoring). The sex-interaction model (C statistic, 0.836) contained sex, age, age × sex, BMI, BMI × sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SA risk calculator: one in English (https://www.montefiore.org/sleepapneariskcalc.html) and another in Spanish (http://www.montefiore.org/sleepapneariskcalc-es.html). CONCLUSIONS: We created an internally validated, highly discriminating, well-calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects

Sleep During Pregnancy: The nuMoM2b Pregnancy and Sleep Duration and Continuity Study

Study Objectives: To characterize sleep duration, timing and continuity measures in pregnancy and their association with key demographic variables. Methods: Multisite prospective cohort study. Women enrolled in the nuMoM2b study (nulliparous women with a singleton gestation) were recruited at the second study visit (16-21 weeks of gestation) to participate in the Sleep Duration and Continuity substudy. Women <18 years of age or with pregestational diabetes or chronic hypertension were excluded from participation. Women wore a wrist activity monitor and completed a sleep log for 7 consecutive days. Time in bed, sleep duration, fragmentation index, sleep efficiency, wake after sleep onset, and sleep midpoint were averaged across valid primary sleep periods for each participant. Results: Valid data were available from 782 women with mean age of 27.3 (5.5) years. Median sleep duration was 7.4 hours. Approximately 27.9% of women had a sleep duration of 9 hours. In multivariable models including age, race/ethnicity, body mass index, insurance status, and recent smoking history, sleep duration was significantly associated with race/ethnicity and insurance status, while time in bed was only associated with insurance status. Sleep continuity measures and sleep midpoint were significantly associated with all covariates in the model, with the exception of age for fragmentation index and smoking for wake after sleep onset. Conclusions: Our results demonstrate the relationship between sleep and important demographic characteristics during pregnancy

A Population‐Based Twin Study on Sleep Duration and Body Composition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93648/1/oby.2011.274.pd

Association of self-reported physical activity with obstructive sleep apnea: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

We examined associations of mild and moderate to severe obstructive sleep apnea (OSA; apnea-hypopnea index ≥5 and ≥15, respectively) with recommended amounts of moderate-vigorous physical activity (MVPA) or vigorous physical activity (VPA) and by type of activity (i.e., recreational, transportation, and work activity). The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter population-based study, enrolled individuals from 2008 to 2011 from four U.S. metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; San Diego, California). Participants in this study included 14,206 self-identified Hispanic/Latino ages 18 to 74 years from theHCHS/SOL. Survey logistic regression analysis was used to compute odds ratios [OR] and 95% confidence intervals [CI], adjusting for sociodemographics, smoking status, and body mass index (BMI). Relative to being inactive, performing some MVPA (>0 to <150 minutes/week) or meeting the recommended MVPA (≥150 minutes/week) were associated with lower odds of mild OSA (ORs and 95% CIs 0.70 [0.61-0.82] and 0.76 [0.63-0.91], respectively), as well as moderate to severe OSA (ORs and 95% CIs 0.76 [0.62-0.93] and 0.76 [0.59-0.98], respectively). Associations of VPA with OSA were not significant. Engaging in medium or high levels of transportation activity was associated with lower odds of mild OSA (OR: 0.84, 95% CI: 0.74-0.96; OR: 0.64, 95% CI: 0.43-0.95, respectively). Performing some recreational MVPA was associated with lower likelihood of mild and moderate to severe OSA (OR: 0.82, 95% CI: 0.71-0.93; OR: 0.79, 95% CI: 0.64-0.97, respectively). Health promotion and OSA prevention efforts should encourage individuals to engage in at least some MVPA

Neighborhood Factors as Predictors of Poor Sleep in the Sueño Ancillary Study of the Hispanic Community Health Study/Study of Latinos

To evaluate whether an adverse neighborhood environment has higher prevalence of poor sleep in a US Hispanic/Latino population