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The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows for wakefulness throughout the day and a long consolidated sleep episode at night. Changes to either the sleep regulatory process or how they interact can result in an inability to fall asleep at the desired time, difficulty remaining asleep, waking too early, and/or difficulty remaining awake throughout the day. This mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep is a hallmark of a class of sleep disorders called the circadian rhythm sleep-wake disorders. In this updated article, we discuss typical changes in the circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep disorders; and how neurologic diseases in older patient impact circadian rhythms and sleep.

Objectives Rotating shift work is associated with adverse outcomes due to circadian misalignment, sleep curtailment, work-family conflicts, and other factors. We tested a bright light countermeasure to enhance circadian adaptation on a counterclockwise rotation schedule. Methods Twenty-nine adults (aged 20–40 years; 15 women) participated in a 4-week laboratory simulation with weekly counterclockwise transitions from day, to night, to evening, to day shifts. Each week consisted of five 8-hour workdays including psychomotor vigilance tests, two days off, designated 8-hour sleep episodes every day, and an assessment of circadian melatonin secretion. Participants were randomized to a treatment group (N=14), receiving intermittent bright light during work designed to facilitate circadian adaptation, or a control group (N=15) working in indoor light. Adaptation was measured by how much of the melatonin secretion episode overlapped with scheduled sleep timing. Results On the last night shift, there was a greater overlap between melatonin secretion and scheduled sleep time in the treatment group [mean 4.90, standard deviation (SD) 2.8 hours] compared to the control group (2.62, SD 2.8 hours; P=0.002), with night shift adaptation strongly influenced by baseline melatonin timing (r 2 =-0.71, P=0.01). While the control group exhibited cognitive deficits on the last night shift, the treatment group’s cognitive deficits on the last night and evening shifts were minimized. Conclusions In this laboratory setting, intermittent bright light during work hours enhanced adaptation to night work and subsequent readaptation to evening and day work. Light regimens scheduled to shift circadian timing should be tested in actual shift workers on counterclockwise schedules as a workplace intervention.

The 2019 coronavirus disease (COVID-19) has become a global health and economic crisis. Recent evidence from small samples suggest that it has increased mood and sleep disturbances, including insomnia, around the world. This study aimed to estimate the effect of COVID-19 on insomnia levels worldwide and in the United States during the acute phase of the pandemic.We analyzed search query data recorded between January 2004 and May 2020 from Google Trends and Google Keyword Planner for the search term "insomnia".The number of search queries for insomnia has increased over the past decade and is greater than the number of search queries for other major sleep disorders. The COVID-19 pandemic increased search queries for insomnia both worldwide and in the United States, with the number in the United States increasing by 58% during the first 5 months of 2020 compared with the same months from the previous 3 years. There is a robust diurnal pattern in insomnia search queries in the United States, with the number of queries peaking around 3 am and the overall pattern remaining stable during the pandemic.These results highlight the impact the COVID-19 pandemic has had on sleep health and the urgent need for making effective interventions accessible. Future studies will be needed to determine whether the increase in insomnia symptoms will persist and lead to higher rates of chronic insomnia in the population.

Circadian misalignment remains a distinct challenge for night shift workers. Variability in individual sleep-wake/light-dark patterns might contribute to individual differences in circadian alignment in night shift workers. In this simulation study, we compared the predicted phase shift from a mathematical model of the effect of light on the human circadian pacemaker to the observed melatonin phase shift among individuals who completed one of four interventions during simulated night shift work. Two inputs to the model were used to simulate circadian phase: sleep-wake/light-dark patterns measured from a wrist monitor (Simulation 1) and sleep-wake/light-dark patterns measured from a wrist monitor enhanced by known light levels measured at the level of the eye during simulated night shifts (Simulation 2). The estimated phase shift from the model was within 2 hours of the observed phase shift in ~80% of night shift workers for both simulations; none of the model-predicted phase shifts was more than ~3 hours from the observed phase shift. Overall, the root-mean-square error between observed and predicted phase shifts was better for Simulation 1. The light input from the wrist monitor informed by actual light level measured at the eye performed better in the sub-group exposed to bright light during their night shifts. The findings from this simulation study suggest that using a mathematical model combined with sleep-wake and light exposure data from a wrist monitor can facilitate the design of shift work schedules to enhance circadian alignment, which is expected to improve sleep, alertness, and performance.

Aging is associated with changes in sleep, and improving sleep may have important consequences for the health, cognition, and quality of life of older adults. Many prescription sleep aids increase the risk of nighttime falls, have adverse effects on next-day cognition, and are associated with increased mortality. Melatonin, a hormone secreted at night, increases sleep duration in young adults but only when administered during the day when endogenous levels are low. In a month-long cross-over study, we randomized 24 healthy older (age55, mean 64.2 ± 6.3 years) participants to receive 2 weeks of placebo and 2 weeks of either a low (0.3 mg) or high (5.0 mg) dose of melatonin 30 min before lights out. Sleep was polysomnographically recorded and was scheduled during both the biological day and night using a forced desynchrony design. Although 0.3 mg melatonin had a trend towards increasing sleep efficiency (SE) overall, this was due to its effects on sleep during the biological day. In contrast, 5 mg melatonin significantly increased SE during both biological day and night, mainly by increasing the duration of Stage 2 non-rapid eye movement sleep and slightly shortening awakenings. Melatonin should be further explored as a sleep aid for older adults.

Chronic sleep restriction (CSR) has been associated with adverse effects including cognitive impairment and increased risk of diabetes and cardiovascular disease. Yet, sleep restriction therapy is an essential component of most behavioral treatments for insomnia. Moreover, little is known about the impact of CSR on sleep continuity and structure in healthy people whose need for sleep is satiated. We investigated the impact of CSR on sleep continuity and structure in nine healthy participants. They had 4 nights of sleep extension, 2 nights of post-extension sleep, 21 nights of CSR (5/5.6-hour time-in-bed), and 9 nights of recovery sleep. Compared to postextension sleep, during CSR sleep duration was reduced by 95.4 ± 21.2 min per night, Slow-Wave Activity was significantly increased, and sleep was more consolidated. During recovery, sleep duration was increased by 103.3 ± 23.8 min compared to CSR, and the CSR-induced increase in Slow-Wave Activity persisted, particularly after the 5-hour exposure. Yet, we found that sustained vigilant attention was not fully recovered even after nine nights of recovery sleep. Our results suggest that CSR improves traditional metrics of sleep quality and may have a persistent impact on sleep depth, which is consistent with the reported benefits on sleep continuity and structure of sleep restriction therapy. However, these improvements in traditional metrics of sleep quality were associated with deterioration rather than improvement in neurobehavioral performance, demonstrating that sleep duration should be included in assessments of sleep quality. These results have implications for the long-term use of sleep restriction in the behavioral treatment of insomnia. Clinical Trial Registration: Impact of Chronic Circadian Disruption vs. Chronic Sleep Restriction on Metabolism (https://clinicaltrials.gov/ct2/show/; #NCT02171273).

Sudden cardiac death (SCD) is the sudden, unexpected death due to abrupt loss of heart function secondary to cardiovascular disease. In certain populations living with cardiovascular disease, SCD follows a distinct 24-hour pattern in occurrence, suggesting day/night rhythms in behavior, the environment, and endogenous circadian rhythms result in daily spans of increased vulnerability. The National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death to identify fundamental questions regarding the role of the circadian rhythms in SCD. Part 2 summarizes research gaps and opportunities in the areas of population and clinical research identified in the workshop. Established research supports a complex interaction between circadian rhythms and physiological responses that increase the risk for SCD. Moreover, these physiological responses themselves are influenced by several biological variables, including the type of cardiovascular disease, sex, age, and genetics, as well as environmental factors. The emergence of new noninvasive biotechnological tools that continuously measure key cardiovascular variables, as well as the identification of biomarkers to assess circadian rhythms, hold promise for generating large-scale human data sets that will delineate which subsets of individuals are most vulnerable to SCD. Additionally, these data will improve our understanding of how people who suffer from circadian disruptions develop cardiovascular diseases that increase the risk for SCD. Emerging strategies to identify new biomarkers that can quantify circadian health (eg, environmental, behavioral, and internal misalignment) may lead to new interventions and therapeutic targets to prevent the progression of cardiovascular diseases that cause SCD.

Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death. We present a 2-part report of findings from this workshop. Part 1 summarizes the workshop and serves to identify research gaps and opportunities in the areas of basic and translational research. Among the gaps was the lack of standardization in animal studies for reporting environmental conditions (eg, timing of experiments relative to the light dark cycle or animal housing temperatures) that can impair rigor and reproducibility. Workshop participants also pointed to uncertainty regarding the importance of maintaining normal circadian rhythmic synchrony and the potential pathological impact of desynchrony on SCD risk. One related question raised was whether circadian mechanisms can be targeted to reduce SCD risk. Finally, the experts underscored the need for studies aimed at determining the physiological importance of circadian clocks in the many different cell types important to normal heart function and SCD. Addressing these gaps could lead to new therapeutic approaches/molecular targets that can mitigate the risk of SCD not only at certain times but over the entire 24-hour period.

Nearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods.We investigated the effects of recurrent circadian disruption (RCD) on glucose metabolism in C57BL/6 mice and in human participants exposed to non-24-h light-dark (LD) schedules vs. those on standard 24-h LD schedules. These LD schedules were designed to induce circadian misalignment between behaviors including rest/activity and fasting/eating with the output of the near-24-h central circadian pacemaker, while minimizing sleep loss, and were maintained for 12 weeks in mice and 3 weeks in humans. We examined interactions of these circadian-disrupted schedules compared to control 24-h schedules with a lower-fat diet (LFD, 13% in mouse and 25-27% in humans) and high-fat diet (HFD, 45% in mouse and 45-50% in humans). We also used young vs. older mice to determine whether they would respond differently to RCD.When combined with a HFD, we found that RCD caused significant weight gain in mice and increased body fat in humans, and significantly impaired glucose tolerance and insulin sensitivity in both mice and humans, but this did not occur when RCD was combined with a LFD. This effect was similar in both young and older mice.These results in both humans and a model organism indicate that circadian disruption has an adverse effect on metabolism among individuals eating a high-fat Western-style diet, even in the absence of significant sleep loss, and suggest that reducing dietary fat may protect against the metabolic consequences of a lifestyle (such as shift work) that involves chronic circadian disruption.

Background: Musculoskeletal disorders (MSDs) are the leading cause of pain and disability among nurses and are frequently accompanied by depression. However, the association between the comorbidity of MSDs and depression and working conditions has not been studied, which was the aim of this study. Methods: In 2015, all nurses ( n = 1,102) employed at a community hospital in the Northeast United States were invited to participate in this cross-sectional study. A survey was distributed in which participants were asked to report on MSDs, depressive symptoms, as well as subjective working conditions assessed including physical demands, psychological demands, decision authority, social support, and work–family conflict. Findings: 397 nurses responded (36%), and the prevalence of the comorbidity of MSDs and depression was 14.5%. Poisson regression (PR) models suggested that work–family conflict was associated with increased risk of the comorbidity (PR = 2.18; 95% confidence interval [CI] = 1.33–3.58), as was 8-hour night shift (PR = 2.77; 95% CI = [1.22, 6.31]) or 12-hour day shift (PR = 2.20; 95% CI = [1.07, 4.50]). Other working conditions were not directly associated with the comorbidity. Conclusions/Application to Practice: The comorbidity of MSDs and depression is prevalent among hospital nurses, and work–family conflict and working night shift or longer shifts were significantly associated with this. Effective workplace programs are needed to address nurses’ working conditions to reduce their work–family conflict, thereby improving their musculoskeletal and mental health.

There are strong individual differences in performance during sleep deprivation. We assessed whether baseline features of Psychomotor Vigilance Test (PVT) performance can be used for classifying participants’ relative attentional vulnerability to total sleep deprivation. In a laboratory, healthy adults (n = 160, aged 18–30 years) completed a 10-min PVT every 2 h while being kept awake for ≥24 hours. Participants were categorized as vulnerable (n = 40), intermediate (n = 80), or resilient (n = 40) based on their number of PVT lapses during one night of sleep deprivation. For each baseline PVT (taken 4–14 h after wake-up time), a linear discriminant model with wrapper-based feature selection was used to classify participants’ vulnerability to subsequent sleep deprivation. Across models, classification accuracy was about 70% (range 65–76%) using stratified 5-fold cross validation. The models provided about 78% sensitivity and 86% specificity for classifying resilient participants, and about 70% sensitivity and 89% specificity for classifying vulnerable participants. These results suggest features derived from a single 10-min PVT at baseline can provide substantial, but incomplete information about a person’s relative attentional vulnerability to total sleep deprivation. In the long term, modeling approaches that incorporate baseline performance characteristics can potentially improve personalized predictions of attentional performance when sleep deprivation cannot be avoided.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

Daily rhythms in several physiological processes are important for cardiometabolic health. The lipid panel is used clinically to assess cardiovascular disease risk, but previous attempts to demonstrate circadian variation in lipids have failed to uncouple the endogenous circadian rhythm from the effects of meals and wake duration. Changes in basal lipid levels and dampening of circadian rhythms have been reported with aging, but it is unknown whether aging is also associated with changes in the rhythmic variation of lipids. We measured fasting lipid panels (triglycerides, total cholesterol, high‐density lipoprotein, and low‐density lipoprotein) in blood at wake time in 21 healthy adults using a specialized laboratory protocol that uncouples sleep–wake and activity‐related effects from the endogenous circadian rhythm. Young and older adults exhibited endogenous circadian variations in fasting triglycerides, with both groups peaking in the early biological morning. Young adults also exhibited significant circadian rhythmicity in total cholesterol and low‐density lipoprotein, while older adults did not exhibit circadian rhythmicity in any other lipids. These results reveal that triglyceride metabolism may be regulated by the central circadian pacemaker. Moreover, our findings may have clinical implications in assessing cardiovascular risk in shift workers and younger adults, since routine measurement of morning/fasting lipids may not fully and reliably assess triglyceride‐ and other lipid‐related biomarkers of cardiovascular disease risk in these groups., Daily rhythms in several physiological processes are important for cardiometabolic health. Young and older adults exhibited endogenous circadian variations in fasting triglycerides, with both groups peaking in the early biological morning. These results reveal that triglyceride metabolism may be regulated by the central circadian pacemaker, and may have clinical implications in assessing cardiovascular risk in shift workers and younger adults.

Age-related disrupted sleep has been associated with modifications in the timing of endogenous circadian rhythms. There are studies suggesting a decreased sensitivity of the aging circadian pacemaker to light. In this study, we aimed to test whether a moderate illuminance light stimulus would produce significant phase shifts in older adults, and whether those would fall in a range consistent with the illuminance response curve (IRC) we previously reported in older adults. We conducted an 8-day in-patient study with 12 healthy older participants (mean age [SD], 58.3 [4.2] y, 5 females). A 6.5-h polychromatic white light exposure with a target illuminance of 270 lux was administered beginning in the early biological night. Before and after the light exposure, a circadian phase estimation procedure was carried out, with plasma melatonin data used as a circadian phase marker. The mean phase delay produced by the light stimulus was 1.78 ± 0.77 h. Ten of the 12 phase delay shifts at ~270 lux fell within the 95% predictive interval of the model fit to data from our previous IRC in older adults. This finding demonstrates that the circadian system of healthy older adults is sensitive to the phase-delaying effects of a moderate intensity light stimulus. The magnitude of the observed phase shifts is consistent with the previously described IRC in older adults.

More than a third of US adults report fewer than 6 hours of sleep a night, making chronic sleep restriction a growing public health concern. Sleep curtailment is associated with an increase in industrial accidents, motor vehicle accidents, medical and other occupational errors. Young adults are more vulnerable to acute sleep deprivation than older adults, but less is known about how young vs. older adults respond to the more commonly experienced chronic sleep restriction. To test the hypothesis that young adults are more vulnerable to chronic sleep loss than older adults, we compared data from young and older adults who underwent three weeks of chronic sleep restriction (equivalent to 5.6 hours/24 hours) combined with recurrent circadian disruption in an experiment that enabled us to separate the influences of the sleep-wake homeostatic process, the circadian timing system, and the chronic sleep deficit. We found that while young and older adults reported similar levels of subjective sleepiness, objective measures of sleepiness revealed that young adults were more vulnerable and had more attentional failures than the older adults. These results have important public health implications, particularly related to prevention of sleep-related motor vehicle crashes in young drivers. Further research is needed to understand the neurobiological basis of these age-related differences.

Nurses are at a high risk for work-family conflict due to long and irregular work hours and multiple physical and psychosocial stressors in their work environment. Nurses report higher rates of depressive symptoms than the general public, leading to a high rate of burnout, absenteeism, and turnover. Work-family conflict is associated with negative consequences in nurses including physical illnesses and mental disorders.Past research on this topic has not examined the mechanisms for the effect of work family conflict on depression. Studies rarely examine the influence of health behaviors such as sleep in explaining this association. Our study identified significant association of sleep disturbances with both work-family conflict and depressive symptoms in nurses. Our main contribution is reporting the important role of sleep disturbances in translating the effect of work-family conflict on depressive symptoms among nurses.Nurses need to receive training in best practices for maintaining their own sleep and mental health. Organizations should include sleep health education and training in workplace health programs. Evidence-based interventions to promote healthy sleep practices such as cognitive behavioral therapy and complementary and integrative approaches should be evaluated for their effectiveness in addressing the impact of work-family conflict on the mental health of nurses. Healthcare organizations should incorporate mental health services as part of their Employee Assistance Program for nurses and include psychological and sleep disorders screening, counseling, and follow-up.Introduction Depression has been identified as the leading cause of disability worldwide. Nurses report higher rates of depression than the general public. Work-family conflict is challenging for nurses and may lead to depression and poor health. However, the mechanisms for the effect of work-family conflict on depression have not been well understood. Aim The objective is to use a cross-sectional design to examine the role of sleep disturbances in the association between work-family conflict and depressive symptoms in nurses. Methods Questionnaires, measuring working conditions, work-family conflict, sleep disturbances and depressive symptoms were collected from 397 nurses at a not-for-profit community hospital in the north-eastern United States. Results We observed a significant association between work-family conflict and depressive symptoms (β = 2.22, p .001) among nurses. Sleep disturbances partially mediated this association by 40.54%. Discussion Sleep disturbances play an important role in translating work-family conflict into depressive symptoms. Implications Evidence-based interventions to promote healthy sleep practices should be evaluated for their effectiveness in addressing the impact of work-family conflict on mental health. Organizations should include sleep education and training as a component of workplace health promotion and employee assistance programmes to mitigate the effect of work-family conflict and promote overall health in nurses.

We explored the predictive value of a neurobehavioral performance assessment under rested baseline conditions (evaluated at 8 hours awake following 8 hours of sleep) on neurobehavioral response to moderate sleep loss (evaluated at 20 hours awake two days later) in 151 healthy young participants (18–30 years). We defined each participant’s response-to-sleep-loss phenotype based on the number of attentional failures on a 10-min visual psychomotor vigilance task taken at 20 hours awake (resilient: less than 6 attentional failures, n = 26 participants; non-resilient: 6 or more attentional failures, n = 125 participants). We observed that 97% of rested participants with 2 or more attentional failures (n = 73 of 151) and 100% of rested participants with 3 or more attentional failures (n = 57 of 151) were non-resilient after moderate sleep loss. Our approach can accurately identify a significant proportion of individuals who are at high risk for neurobehavioral performance impairment from staying up late with a single neurobehavioral performance assessment conducted during rested conditions. Additional methods are needed to predict the future performance of individuals who are not identified as high risk during baseline.

Sleep has been demonstrated to improve consolidation of many types of new memories. However, few prior studies have examined how sleep impacts learning of face-name associations. The recognition of a new face along with the associated name is an important human cognitive skill. Here we investigated whether post-presentation sleep impacts recognition memory of new face-name associations in healthy adults. Fourteen participants were tested twice. Each time, they were presented 20 photos of faces with a corresponding name. Twelve hours later, they were shown each face twice, once with the correct and once with an incorrect name, and asked if each face-name combination was correct and to rate their confidence. In one condition the 12-h interval between presentation and recall included an 8-h nighttime sleep opportunity (“Sleep”), while in the other condition they remained awake (“Wake”). There were more correct and highly confident correct responses when the interval between presentation and recall included a sleep opportunity, although improvement between the “Wake” and “Sleep” conditions was not related to duration of sleep or any sleep stage. These data suggest that a nighttime sleep opportunity improves the ability to correctly recognize face-name associations. Further studies investigating the mechanism of this improvement are important, as this finding has implications for individuals with sleep disturbances and/or memory impairments.

ObjectivesThis study investigated whether an intervention designed to reduce homeostatic sleep pressure would improve night shift performance and alertness in older adults.MethodsNon-shift workers aged 57.9±4.6 (mean±SD) worked four day (07:00–15:00) and four night shifts (23:00–07:00). Two intervention groups were instructed to remain awake until ~13:00 after each night shift: the sleep timing group (ST; n=9) was instructed to spend 8 hours in bed attempting sleep, and the sleep ad-lib group (n=9) was given no further sleep instructions. A control group (n=9) from our previous study was not given any sleep instructions. Hourly Karolinska Sleepiness Scales and Psychomotor Vigilance Tasks assessed subjective sleepiness and performance.ResultsThe ST group maintained their day shift sleep durations on night shifts, whereas the control group slept less. The ST group were able to maintain stable performance and alertness across the initial part of the night shift, while the control group’s alertness and performance declined across the entire night. Wake duration before a night shift negatively impacted sustained attention and self-reported sleepiness but not reaction time, whereas sleep duration before a night shift affected reaction time and ability to sustain attention but not self-reported sleepiness.ConclusionsA behavioural change under the control of the individual worker, spending 8 hours in bed and waking close to the start of the night shift, allowed participants to acquire more sleep and improved performance on the night shift in older adults. Both sleep duration and timing are important factors for night shift performance and self-reported sleepiness.

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.

Summary There is emerging evidence that circadian misalignment may alter energy expenditure, leading to obesity risk among those with irregular schedules [ 1 , 2 , 3 , 4 , 5 ]. It has been reported that energy expenditure is affected by the timing of sleep, exercise, and meals [ 6 ]. However, it is unclear whether the circadian system also modulates energy expenditure, independent of behavioral state and food intake. Here, we used a forced desynchrony protocol to examine whether fasted resting energy expenditure (REE) varies with circadian phase in seven participants. This protocol allowed us to uncouple sleep-wake and activity-related effects from the endogenous circadian rhythm, demonstrating that REE varies by circadian phase. REE is lowest at circadian phase ∼0°, corresponding to the endogenous core body temperature (CBT) nadir in the late biological night, and highest at circadian phase ∼180° in the biological afternoon and evening. Furthermore, we found that respiratory quotient (RQ), reflecting macronutrient utilization, also varies by circadian phase. RQ is lowest at circadian phase ∼240° and highest at circadian phase ∼60°, which corresponds to biological morning. This is the first characterization of a circadian profile in fasted resting energy expenditure and fasted respiratory quotient (with rhythmic profiles in both carbohydrate and lipid oxidation), decoupled from effects of activity, sleep-wake cycle, and diet in humans. The rhythm in energy expenditure and macronutrient metabolism may contribute to greater weight gain in shift workers and others with irregular schedules.

OBJECTIVES: Exposure to light can have acute alerting and circadian phase-shifting effects. This study investigated the effects of evening exposure to blue-enriched polychromatic white (BEL) vs. polychromatic white light (WL) on sleep inertia dissipation the following morning in older adults. METHODS: Ten healthy older adults (average age = 63.3 yrs; 6F) participated in a 13-day study comprising three baseline days, an initial circadian phase assessment, four days with 2-h evening light exposures, a post light exposure circadian phase assessment and three recovery days. Participants were randomized to either BEL or WL of the same irradiance for the four evening light exposures. On the next mornings at 2, 12, 22 and 32 minutes after each wake time, the participants completed a 90-s digit-symbol substitution test (DSST) to assess working memory, and objective alertness was assessed using a wake EEG recording. DSST and power density from the wake EEG recordings were compared between the two groups. RESULTS: DSST performance improved with time awake (p< 0.0001) and across study days in both light exposure groups (p< 0.0001). There was no main effect of group, although we observed a significant day × group interaction (p=0.0004), whereby participants exposed to BEL performed significantly better on the first two mornings after light exposures than participants in WL (post-hoc, p< 0.05). On those days, the BEL group showed higher EEG activity in some of the frequency bins in the sigma and beta range (p

Aging is associated with a marked increase in sleep complaints, and one factor causing sleep disruption is waking to void (nocturia). Urological surveys have found that few young adults report nocturia symptoms, but about half of those in their 60's and nearly 80% of older age groups are affected. Sleep surveys have found nocturia is a major cause of sleep disruption, with a majority of older adults with sleep disruption citing the need to void as the cause of their awakening. While much of the urological literature implies that nocturia causes sleep disruption, age-related changes in sleep depth and continuity may make it more likely that an older adult will wake in response to a filling bladder, or that an older adult will wake for another reason and then decide to void. There is also evidence that age-related changes in the amplitude of circadian rhythms contribute to nocturia. There is a well-described circadian rhythm in urine output, and evidence of circadian rhythmicity in some diuretic and anti-diuretic hormones. In this article, we describe how age-related changes in sleep depth and continuity and age-related changes in circadian rhythm amplitude may contribute to nocturia, and how nocturia in turn leads to sleep disruption. Better understanding of how changes in sleep and circadian rhythmicity impact nocturia may lead to improved treatments and better quality of life for older adults.

Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. This article reviews key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep.

Access to electric light might have shifted the ancestral timing and duration of human sleep. To test this hypothesis, we studied two communities of the historically hunter-gatherer indigenous Toba/Qom in the Argentinean Chaco. These communities share the same ethnic and sociocultural background, but one has free access to electricity while the other relies exclusively on natural light. We fitted participants in each community with wrist activity data loggers to assess their sleep-wake cycles during one week in the summer and one week in the winter. During the summer, participants with access to electricity had a tendency to a shorter daily sleep bout (43 ± 21 min) than those living under natural light conditions. This difference was due to a later daily bedtime and sleep onset in the community with electricity, but a similar sleep offset and rise time in both communities. In the winter, participants without access to electricity slept longer (56 ± 17 min) than those with access to electricity, and this was also related to earlier bedtimes and sleep onsets than participants in the community with electricity. In both communities, daily sleep duration was longer during the winter than during the summer. Our field study supports the notion that access to inexpensive sources of artificial light and the ability to create artificially lit environments must have been key factors in reducing sleep in industrialized human societies. Fil: De La Iglesia, Horacio O.. University of Washington; Estados Unidos Fil: Fernandez Duque, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; Argentina. Universidad Nacional de Formosa. Facultad de Recursos Naturales; Argentina. University of Yale; Estados Unidos Fil: Golombek, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina Fil: Lanza, Norberto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Investigaciones Geohistóricas. Universidad Nacional del Nordeste. Instituto de Investigaciones Geohistóricas; Argentina Fil: Duffy, Jeanne F.. Harvard Medical School; Estados Unidos Fil: Czeisler, Charles A.. Harvard Medical School; Estados Unidos Fil: Valeggia, Claudia Rita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows wakefulness throughout the day and a long consolidated sleep episode at night. Mismatch between the desired timing of sleep and the ability to fall and remain asleep is a hallmark of the circadian rhythm sleep-wake disorders. This article discusses changes in circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep-wake disorders; and how neurologic diseases in older patients affect circadian rhythms and sleep.

Soluble IL-13 receptor-α1, or sIL13rα1, is a soluble protein that binds to interleukin-13 (IL-13) that has been previously described in mice. The function of sIL13rα1 remains unclear, but it has been hypothesized to act as a decoy receptor for IL-13. Recent studies have identified a role for IL-13 in glucose metabolism, suggesting that a decoy receptor for IL-13 might increase circulating glucose levels. Here, we report that delivery of sIL13rα1 to mice by either gene transfer or recombinant protein decreases blood glucose levels. Surprisingly, the glucose-lowering effect of sIL13rα1 was preserved in mice lacking IL-13, demonstrating that IL-13 was not required for the effect. In contrast, deletion of IL-4 in mice eliminated the hypoglycemic effect of sIL13rα1. In humans, endogenous blood levels of IL13rα1 varied substantially, although there were no differences between diabetic and nondiabetic patients. There was no circadian variation of sIL13rα1 in normal human volunteers. Delivery of sIL13rα1 fused to a fragment crystallizable (Fc) domain provided sustained glucose lowering in mice on a high-fat diet, suggesting a potential therapeutic strategy. These data reveal sIL13rα1 as a circulating human protein with an unexpected role in glucose metabolism.

Poor sleep is increasingly being recognised as an important prognostic parameter of health. For those with suspected sleep disorders, patients are referred to sleep clinics which guide treatment. However, sleep clinics are not always a viable option due to their high cost, a lack of experienced practitioners, lengthy waiting lists and an unrepresentative sleeping environment. A home-based non-contact sleep/wake monitoring system may be used as a guide for treatment potentially stratifying patients by clinical need or highlighting longitudinal changes in sleep and nocturnal patterns. This paper presents the evaluation of an under-mattress sleep monitoring system for non-contact sleep/wake discrimination. A large dataset of sensor data with concomitant sleep/wake state was collected from both younger and older adults participating in a circadian sleep study. A thorough training/testing/validation procedure was configured and optimised feature extraction and sleep/wake discrimination algorithms evaluated both within and across the two cohorts. An accuracy, sensitivity and specificity of 74.3%, 95.5%, and 53.2% is reported over all subjects using an external validationdataset (71.9%, 87.9% and 56%, and 77.5%, 98% and 57% is reported for younger and older subjects respectively). These results compare favourably with similar research, however this system provides an ambient alternative suitable for long term continuous sleep monitoring, particularly amongst vulnerable populations.

Work-related musculoskeletal disorders (WMSDs) persist as the leading occupational injury, accounting for nearly half of nurses’ total occupational injuries. Musculoskeletal pain is a known cause of sleep disruption, and individuals with WMSDs that interfere with sleep often report more pain. Evening chronotype has been associated with poor sleep among nurses. However, the associations among chronotype, sleep, and WMSDs are still unclear, and were explored in the present study. A cross-sectional survey was administered to 397 nurses, with 47.4% reporting WMSDs. Robust Poisson regression modeling suggested that evening type (PR = 1.32, p < .05), prolonged sleep onset latency (PR = 1.37, p < .05), and using sleep-promoting substances (PR = 1.35, p < .01) were associated with increased risk of WMSDs among nurses, after adjusting for shift work, regular exercise, body mass index, and other covariates. This study suggests that well-designed evidence-based nonpharmacological interventions to improve sleep may reduce the risk of WMSDs among nurses.

In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength-enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next-morning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety.

Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1 -2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results.

Objectives: To evaluate associations between sleep duration at midlife and later life and change in sleep duration over time and cognition in older women. Design: Participants reported sleep duration in 1986 and 2000, and a subgroup of older participants began cognitive testing in 1995 to 2001; follow-up testing was conducted three times, at 2-year intervals. Setting: Prospective Nurses' Health Study cohort. Participants: Female nurses aged 70 and older free of stroke and depression at the initial cognitive assessment (N = 15,385). Measurements: Validated, telephone-based cognitive battery to measure cognitive function; four repeated assessments over 6 years were averaged to estimate overall cognition at older ages, and trajectories of cognitive change were evaluated over follow up. Results: Extreme sleep durations in later life were associated with worse average cognition (P < .001 for the quadratic term for a global score averaging all six cognitive tests). For example, women sleeping 5 h/d or less had worse global cognition than those sleeping 7 h/d, as did women sleeping 9 h/d or more; differences were equivalent to nearly 2 additional years of age. Associations were similar, although slightly attenuated, for sleep duration in midlife. Women whose sleep duration changed by 2 h/d or more over time had worse cognition than women with no change in sleep duration (e.g., for the global score, P < .001 for the quadratic term). Sleep duration was not associated with trajectories of cognitive function over 6 years, which might be attributable to short follow-up for detecting cognitive decline. Conclusion: Extreme sleep durations at midlife and later life and extreme changes in sleep duration over time appear to be associated with poor cognition in older women.

Studies using self-report and physiological markers of circadian rhythmicity have demonstrated sex differences in a number of circadian attributes including morningness-eveningness, entrained phase, and intrinsic period. However, these sex differences have not been examined at the level of the molecular clock and not in human cerebral cortex. The authors tested the hypothesis that there are detectable daily rhythms of clock gene expression in human cerebral cortex and that there are significant sex differences in the timing of these rhythms. The expression levels of 3 clock genes— PER2, PER3, and ARNTL1—were quantified in samples of dorsolateral prefrontal cortex from 490 deceased individuals in 2 cohort studies of older individuals, the Religious Orders Study and the Rush Memory and Aging Project, using mRNA microarray data. Clock gene expression at death was parameterized as a function of time of death using cosine curves and was examined for sex differences in the phase of these curves. Significant daily variation was seen in the expression of PER2 ( p = 0.004), PER3 ( p = 0.003), and ARNTL1 ( p = 0.0005). PER2/3 expression peaked at 10:38 (95% confidence interval [CI], 09:20-11:56) and 10:44 (95% CI, 09:29-11:59), respectively, and ARNTL1 expression peaked in antiphase to this at 21:23 (95% CI, 20:16-22:30). The timing of the expression of all 3 genes was significantly earlier in women than in men ( PER2 6.8 h, p = 0.002; PER3 5.5 h, p = 0.001; ARNTL1 4.7 h, p = 0.007). Daily rhythms of clock gene expression are present in human cerebral cortex and can be inferred from postmortem samples. Moreover, these rhythms are relatively delayed in men compared with women.

A common complaint of older persons is disturbed sleep, typically characterized as an inability to return to sleep after waking. As every sleep episode (i.e., time in bed) includes multiple transitions between wakefulness and sleep (which can be subdivided into rapid eye movement [REM] sleep and non-REM [NREM] sleep), we applied survival analysis to sleep data to determine whether changes in the "hazard" (duration-dependent probability) of awakening from sleep and/or returning to sleep underlie age-related sleep disturbances. The hazard of awakening from sleep-specifically NREM sleep-was much greater in older than in young adults. We found, however, that when an individual had spontaneously awakened, the probability of falling back asleep was not greater in young persons. Independent of bout length, the number of transitions between NREM and REM sleep stages relative to number of transitions to wake was approximately 6 times higher in young than older persons, highlighting the difficulty in maintaining sleep in older persons. Interventions to improve age-related sleep complaints should thus target this change in awakenings. © 2013 Elsevier Inc.

The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.21 ± 2.97 years) of European ancestry. A common variant in Period2 (PER2) was associated with 20 min less slow-wave sleep (SWS) in carriers of the minor allele than in noncarriers, representing a 22% reduction in SWS duration. Moreover, spectral analysis in a subset of participants (n = 37) showed the same PER2 polymorphism was associated with reduced EEG power density in the low delta range (0.25-1.0 Hz) during non-REM sleep and lower slow-wave activity (0.75-4.5 Hz) in the early part of the sleep episode. These results indicate the involvement of PER2 in the homeostatic process of sleep. Additionally, a rare variant in Melatonin Receptor 1B was associated with longer REM sleep latency, with minor allele carriers exhibiting an average of 65 min (87%) longer latency from sleep onset to REM sleep, compared to noncarriers. These findings suggest that circadian-related genes can modulate sleep architecture and the sleep EEG, including specific parameters previously implicated in the homeostatic regulation of sleep.

Objective: Circadian rhythms influence the timing of behavior, neurological diseases, and even death. Rare mutations in homologs of evolutionarily conserved clock genes are found in select pedigrees with extreme sleep timing, and there is suggestive evidence that certain common polymorphisms may be associated with self-reported day/night preference. However, no common polymorphism has been associated with the timing of directly observed human behavioral rhythms or other physiological markers of circadian timing at the population level. Methods: We performed a candidate gene association study with replication, evaluating associations between polymorphisms in homologs of evolutionarily conserved clock genes and the timing of behavioral rhythms measured by actigraphy. For validated polymorphisms, we evaluated associations with transcript expression and time of death in additional cohorts. Results: rs7221412, a common polymorphism near period homolog 1 (PER1), was associated with the timing of activity rhythms in both the discovery and replication cohorts (joint p ¼ 2.1 � 10 � 7 ). Mean activity timing was delayed by 67 minutes in rs7221412 GG versus rs7221412 AA homozygotes. rs7221412 also showed a suggestive time-dependent relationship with both cerebral cortex (p ¼ 0.05) and CD14 þ CD16 � monocyte (p ¼ 0.02) PER1 expression and an interesting association with time of death (p ¼ 0.015) in which rs7221412 GG individuals had a mean time of death nearly 7 hours later than rs7221412 AA/AG . Interpretation: A common polymorphism near PER1 is associated with the timing of human behavioral rhythms, and shows evidence of association with time of death. This may be mediated by differential PER1 expression. These results may facilitate individualized scheduling of shift work, medical treatments, or monitoring of vulnerable patient populations. ANN NEUROL 2012;72:324–334

Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages. Ten healthy older adults with sleep complaints (mean age=63.3 years; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5-8 the subjects were exposed for 2h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed. Subjective alertness and wake EEG activity in the alpha range (9.75-11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p

The Stroop color-naming task is one of the most widely studied tasks involving the inhibition of a prepotent response, regarded as an executive function. Several studies have examined performance on versions of the Stroop task under conditions of acute sleep deprivation. Though these studies revealed effects on Stroop performance, the results often do not differentiate between general effects of sleep deprivation on performance and effects specifically on interference in the Stroop task. To examine the effect of prolonged wakefulness on performance on the Stroop task, we studied participants in a 40-hour “constant routine” protocol during which they remained awake in constant conditions and performed a Stroop color-naming task every two hours. We found that reaction time was slowest when the color and word did not match (incongruent), fastest when the color and word did match (congruent), and intermediate when participants named the color of the non-word stimulus (neutral). Performance on all three trial types degraded significantly as a function of time awake. Extended wakefulness did not significantly change the additional time needed respond when the color and word did not match (Stroop interference), nor did it change the amount of facilitation when color and word matched. These results indicate that one night of sleep deprivation influences performance on the Stroop task by an overall increase in response time, but does not appear to impact the underlying processes of interference or facilitation. The results suggest that the degree to which an “executive function” is affected by sleep deprivation may depend on the particular executive function studied and the degree to which it is subserved by the prefrontal cortex.

Genetic association studies of the CLOCK 3111C/T polymorphism and diurnal preference have yielded conflicting results since the first report that the 3111C allele was associated with eveningness. The goal of the present study was to investigate the association of this polymorphism with diurnal preference and circadian physiology in a group of 179 individuals, by comparing the frequency of the 3111C allele to diurnal preference, habitual sleep timing, circadian phase markers, and circadian period. We did not find a significant association between this allele and morningness/eveningness or any circadian marker.

Recent studies have demonstrated that use of light‐emitting (LE) electronic devices in the evening close to bedtime negatively affects physiology and behavior, especially that of sleep and circadian rhythms (Bonnefond et al. 2006; Van den Bulck 2007; Cajochen et al. 2011; Munezawa et al. 2011; Arora et al. 2013, 2014; Czeisler 2013; Foley et al. 2013; Wood et al. 2013; Gamble et al. 2014; Heath et al. 2014; Chang et al. 2015; Carter et al. 2016; Czeisler and Shanahan 2016). Rapid technological advances and market pressures have led to near ubiquitous use of LE‐devices (e.g., desktop, laptop, and tablet computers, cell/smart phones, televisions, and video games) in the modern home and workplace; and such devices are now integral to many daily functions including communication, commerce, recreation, and access to news and information. Greater utility, availability, and portability of LE‐devices have additionally led to widespread LE‐device use in the evening and incorporation into the bedtime routine. A recent National Sleep Foundation survey found that 90% of Americans reported use of LE‐devices within an hour of their bedtimes, and greater use was associated with worse sleep outcomes at all ages (Gradisar et al. 2013). That and other studies have shown that adolescents and young adults are particularly likely to use LE‐devices before bedtime, often multiple LE‐devices at the same time, and the amount of LE‐device use in the evening is associated with multiple negative outcomes including delayed bedtimes, longer sleep latencies, sleep interruption from the LE‐devices during the night, shorter sleep durations, increased daytime sleepiness, and even obesity (Van den Bulck 2007; Munezawa et al. 2011; Arora et al. 2013, 2014; Foley et al. 2013; Gradisar et al. 2013; Gamble et al. 2014; Pourzanjani et al. 2015; Carter et al. 2016; Czeisler and Shanahan 2016). Light exposure per se is thought to cause many of the negative effects from evening use of LE‐devices. Retinal photoreceptors transmit light information to the master circadian clock in the hypothalamus, the suprachiasmatic nucleus (SCN), which regulates secretion of the pineal hormone melatonin together with rhythms in physiology and behavior including sleep, metabolism, immunity, alertness, and performance (Goel et al. 2013; Scheiermann et al. 2013; Qian and Scheer 2016). In the evening hours around bedtime, light exposure suppresses melatonin secretion and causes a phase delay shift in circadian rhythm timing such that melatonin secretion is reset to begin at a later time on subsequent nights (an effect similar to jet lag from extending daylight exposure later due to westward travel) (Khalsa et al. 2003; St Hilaire et al. 2012). This in turn can induce misalignment between the timing of the circadian rhythm of sleep propensity and the timing of sleep, reducing the duration, and quality of sleep (Czeisler et al. 1980; Dijk and Czeisler 1994). Misalignment can also cause delays in bedtime which, especially in children and adolescents, are associated with worse outcomes including behavioral risk factors and mental health problems such as depression (Gangwisch et al. 2010; Lemola et al. 2015; McGlinchey and Harvey 2015). There are also acute effects of light exposure that increase physiological and subjective levels of alertness (Lockley et al. 2006; Cajochen 2007; Rahman et al. 2014), which may impact when an individual feels tired and chooses to go to sleep when they are exposed to light in the evening. Furthermore, the effects of light on sleep, alertness, and circadian physiology are even greater from light exposures that are brighter, longer in duration, timed later in the evening, and contain short‐wavelength light (Lewy et al. 1980; Zeitzer et al. 2000; Brainard et al. 2001; Thapan et al. 2001; Khalsa et al. 2003; Lockley et al. 2006; Cajochen 2007; Santhi et al. 2012; St Hilaire et al. 2012; Lucas et al. 2014; Rahman et al. 2014). Because LE‐devices are often used for extended periods close to bedtime and their screens are typically illuminated by light‐emitting diodes (LED) that are rich in short‐wavelength light (Chang et al. 2015; Gringras et al. 2015) to which the human circadian system is particularly sensitive (Brainard et al. 2001; Thapan et al. 2001; Lockley et al. 2003; Ruger et al. 2013), their use is likely to increase alertness and impact sleep. Our group reported findings from a laboratory‐controlled, within‐subject, counter‐balanced, and randomized study in which the effects of light exposure from five consecutive evenings of reading on a LE‐tablet computer were compared to five consecutive evenings reading from printed books prior to a strictly imposed 10 pm bedtime, followed by an 8‐h scheduled sleep episode in total darkness (Chang et al. 2015). Compared to the evenings with printed books, the LE‐tablet reading condition caused significant melatonin suppression, circadian phase delay shifts, longer sleep latencies, reduced rapid eye movement (REM) sleep, increased alertness prior to bedtime, and lower next‐morning alertness. Those findings provided direct evidence that the light exposure from a tablet computer negatively affected sleep, circadian rhythms, and alertness under controlled laboratory conditions. In that study, the duration of evening reading sessions was set to four hours, bedtimes were fixed at 22:00, and in the LE‐tablet condition the device was placed at a fixed distance from participants and activities were restricted to reading electronic books (eBooks). Other studies that tested the effects of LE‐devices have similarly controlled aspects of the duration, timing, illuminance, and screen content of light exposures (Cajochen et al. 2011; Wood et al. 2013; Heath et al. 2014; van der Lely et al. 2015; Gronli et al. 2016). Now that the effects of LE‐devices on sleep, circadian rhythms, and alertness have been established even when bedtimes are held at a fixed time under controlled laboratory conditions, it is critical to evaluate the impact of LE‐devices on self‐selected bedtimes, sleep, alertness, and circadian rhythms in a randomized trial under controlled laboratory conditions. Increased evening alertness, melatonin suppression, and delayed circadian rhythm timing are likely key factors contributing to epidemiological findings showing associations between evening LE‐device use and later bedtimes (Foley et al. 2013; Gamble et al. 2014; Hysing et al. 2015). Additionally, such devices have numerous capabilities (e.g., internet, email, social media, games, videos, calendar, live streaming). Personal engagement with the diverse available activities may contribute to the selection of later bedtimes, thereby further prolonging evening light exposure from the device, and potentially leading to similar or even greater effects on sleep and circadian rhythms as those already observed under conditions with fixed bedtimes and light exposures. Therefore, in a follow‐up investigation to Chang et al. (Chang et al. 2015) we utilized a similar study design under controlled laboratory conditions, while allowing participants to self‐select their nightly bedtimes and LE‐tablet activities. We aimed to test whether under these unrestricted conditions, evening use of LE‐tablets compared to reading printed materials would affect self‐selection of bedtimes, and influence melatonin secretion, sleep, circadian timing, and alertness.

Aging is associated with an earlier timing of circadian rhythms and a shorter phase angle between wake time and the timing of melatonin secretion or the core body temperature nadir. Light has a phase-dependent effect on the circadian pacemaker, and modifications of habitual light exposure in older people could contribute to a change in the timing of circadian rhythms or in the phase angle of entrainment. In this study, we compare natural light exposure of community-dwelling older and young subjects studied at the same time of year, focusing on the pattern of light exposure across the waking day. We recorded light exposure data for 3 to 8 days from 22 older (aged 66.01 ± 5.83) and 22 young subjects (aged 23.41 ± 4.57), living at home on self-selected sleepwake schedules, and matched for time of year. All subjects were from New England (latitude 42.3° N to 43° N). We compared the percentage of the waking day spent by older and young subjects at 4 different light levels (from very dim to very bright). We compared hourly averaged light exposure data in each group according to clock time and with respect to each subject’s daily sleepwake times. Although both age groups spent more than half of their waking hours in dim or moderate room light intensity (

Healthy aging is associated with changes in sleep-wake regulation, and those changes often lead to problems sleeping, both during the night and during daytime. We aimed to examine the electroencephalographic (EEG) sleep spectra during non-rapid eye movement (NREM) sleep when sleep was scheduled at all times of day.After three 24-h baseline (BL) days, participants were scheduled to live on 20-hour "days" consisting of 6.7 hours of bed rest and 13.3 hours of wakefulness for 12 consecutive days (forced desynchrony, FD). The EEG was recorded from a central derivation during all scheduled sleep episodes, with subsequent visual scoring and spectral analysis.Intensive Physiological Monitoring Unit of the BrighamWomen's Hospital General Clinical Research Center.Twenty-four healthy older subjects (64.2 +/- 6.3 yr; 13 women, 11 men)Compared with BL nights, EEG activity in the slow wave (0.5 to 5.25 Hz), theta (6 to 6.25 and 7 Hz), alpha (10 to 11.25 Hz), and high spindle range (14.5 to 15.5 Hz) was significantly greater during FD, when subjects slept across many times of day and night. During FD, there was a significant interaction between homeostatic and circadian factors, such that EEG delta activity (0.5 to 1.5 Hz) was higher in the biological morning/early afternoon than at other times. EEG activity was significantly increased in almost all frequency ranges (0.5 to 21 Hz) during the biological day, as compared with the biological night, except for the lower EEG spindle range (12.25 to 14 Hz). Overall, EEG beta activity was positively correlated with wakefulness and negatively correlated with total sleep time.Our findings provide some new evidence for the underlying mechanisms that contribute to age-related difficulties in sleep consolidation, especially when sleep occurs during the daytime.

IN MAMMALS, THE SUPRACHIASMATIC NUCLEUS IS A CENTRAL NEURAL PACEMAKER THAT GENERATES CIRCADIAN RHYTHMS IN PHYSIOLOGIC AND BEHAV-IORAL measures, including the timing of sleep, hormone production, body temperature, and waking neurobehavioral performance.1–4 Studies of humans isolated from daily changes in the environment have led to the realization that the timing and organization of sleep, alertness, and performance vary with the circadian phase of the underlying, near 24-hour oscillation.5–7 Neurobehavioral performance in many sleep-deprivation studies has also been reported to be closely linked to homeostatic factors influenced by the duration of prior wakefulness.8 Previous studies have suggested that it is the precise balance between sleep-wake homeostatic factors and the circadian rhythm of alertness and sleep propensity that allow for stable alertness and performance throughout the waking day during entrainment.9–11 A recent study in which chronic misalignment between internal biologic time and the imposed sleep-wake schedule was imposed across 4 weeks showed that cognitive performance (i.e., learning) was significantly impaired, whereas subjects in the same study who remained entrained improved their performance.12 Using forced desynchrony (FD) studies, the circadian modulation of performance and alertness has been revealed.9,13–15 A 28-hour FD protocol has shown that, even within the range of 0 to 18 hours of wakefulness, the contribution of the circadian system to variations of alertness and performance is approximately equal to the contribution of the sleep-wake homeostat in young subjects.10 A study using a 20-hour FD protocol (with a 13.7-hour wake episode) also found circadian modulation of alertness and several aspects of cognitive performance.14 Previous 28-hour FD studies have found that, when scheduled to sleep at an adverse circadian phase, healthy young adults cannot take advantage of the 9.33-hour sleep opportunity on every night.16,17 In fact, when the end of the scheduled sleep episode is at an adverse circadian phase (beginning in the biological daytime between about 110° and 290°), the latter quarter of the scheduled sleep episode is severely disrupted, with sleep efficiency averaging below 70%.17 However, how that lost sleep then impacts subsequent sleep and wake episodes and daytime performance was not explored in those studies. A widely used performance test in studies of circadian rhythms or sleep deprivation is the Psychomotor Vigilance Task (PVT).18 This task has been reported to show no long-lasting training effects.8,18 In contrast, many other performance tests do have learning or practice effects, whereby, with repeated practice, performance on the task gradually improves.12,19,20 Therefore, consideration of those learning or practice effects should be made in analyzing data from long-duration studies. In a preliminary report, we found that a calculation performance task, a test of throughput, showed learning effects across a 4-week FD study, in which a saturating exponential function provided the best fit to the data for all subjects.21 Most prior studies in which both circadian and wake-dependent influences on performance have been assessed were of a 1- to 4-week duration. In the study we report here, subjects participated in a 6-week 28-hour FD study designed to assess circadian period estimates. Several performance measures were given to the subjects throughout the protocol. To examine the practice effects on a calculation performance test, we included a similar addition task that had been used in our prior preliminary report.21 We also included the PVT, given the prior reports suggesting that it has no such practice effects. We aimed to examine whether performance on the addition and PVT would show significant changes across the 6-week FD study, as well as to analyze the circadian and wake-dependent homeostatic modulation on both types of performance, taking into account interindividual differences.

Older adults have reduced sleep quality compared to younger adults when sleeping at habitual times, and greater sleep disruption when their sleep is at adverse times. The purpose of this analysis was to investigate how subjective measures of sleep relate to objectively-recorded sleep in older subjects scheduled to sleep at all times of day. We analyzed data from 24 healthy older (55–74 years) subjects who took part in a 32-day inpatient study where polysomnography (PSG) was recorded each night and subjective sleep was assessed after each scheduled wake time. The study included baseline nights and a forced desynchrony (FD) protocol when the subjects lived on a 20-hr rest-activity schedule. Our post-sleep questionnaire both included quantitative and qualitative questions about the prior sleep. Under baseline and FD conditions, objective and subjective sleep latency were correlated, subjective sleep duration was related to slow wave sleep and wake after sleep onset, subjective sleep quality was related to Stage 1 and 2 sleep, and sleepiness and refreshment at wake time were related to duration of premature awakening. During FD, most measures of objective and subjective sleep varied with circadian phase, and many additional correlations between objective and subjective sleep were present. Our findings show that when sleeping at habitual times, these healthy older subjects did not perceive their generally poor sleep quality, but under FD conditions where sleep quality changed from day-to-day their subjective sleep ratings were more associated with their objective sleep.

The light-dark cycle is the primary synchronizing factor that keeps the internal circadian pacemaker appropriately aligned with the environmental 24-h day. Although it is known that ocular light exposure can effectively shift the human circadian pacemaker and do so in an intensity-dependent manner, the curve that describes the relationship between light intensity and pacemaker response has not been fully characterized for light exposure in the late biological night. We exposed subjects to 3 consecutive days of 5 h of experimental light, centered 1.5 h after the timing of the fitted minimum of core body temperature, and show that such light can phase advance shift the human circadian pacemaker in an intensity-dependent manner, with a logistic model best describing the relationship between light intensity and phase shift. A similar sigmoidal relationship is also observed between light intensity and the suppression of plasma melatonin concentrations that occurs during the experimental light exposure. As with a simpler, 1-day light exposure during the early biological night, our data indicate that the human circadian pacemaker is highly sensitive even to typical room light intensities during the late biological night, with ∼100 lux evoking half of the effects observed with light 10 times as bright.

Shift work results in a misalignment between circadian timing and the sleep/wake schedule, leading to irregular and poor quality sleep. Inconsistent input from the daily light cycle further interferes with circadian entrainment. It has been hypothesized that scheduling the sleep/dark cycle on the night shift could aid in promoting adaptation to night shift work by facilitating appropriate phase shifts. In a simulated shift-work study, we compared the ability of two sleep/dark schedules to shift circadian phase. Our results indicate that scheduled sleep/darkness can aid in adaptation to night shift work by inducing both advance and delay phase shifts, depending on the timing of the sleep schedule, although the size of the phase shifts are not sufficient to produce complete adaptation to the night shift. These results have applications to night shift workers, particularly in occupations in which alterations in the timing of light exposure cannot be achieved during working hours.

Aging is associated with specific sleep complaints, including earlier awakening and decreased sleep consolidation at the end of the night. The circadian pacemaker influences sleep timing and consolidation, and it has been hypothesized that a change in the circadian timing system may contribute to age-related changes in sleep. Here, we examined the relationship between circadian period and wake time, circadian phase, and diurnal preference (morningness–eveningness) in older subjects, and found no significant correlation between those measures, in contrast to our findings from young subjects. These results provide further evidence that the interaction between the circadian system and sleep–wake timing is altered in aging, and suggest that a shortening of circadian period with age cannot account for the advanced circadian phase and earlier wake times of older subjects.

A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate regular environmental rhythms promotes optimal performance and survival. Herein we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s.

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.