Feasibility, effectiveness, and acceptability of an afternoon-evening sleep schedule in older nightshift workers.

Study Objectives: To explore the feasibility, effectiveness, and acceptability of an afternoon-evening sleep schedule in older (age 50-65 years) nightshift workers. Methods: We used a three-part strategy: a screening survey to identify individuals who said they could adopt an 8-hour afternoon-evening sleep schedule; a field study where daily diary and actigraphy data were collected during a baseline week and intervention week, with randomization to self-selected sleep, 8-hour afternoon-evening time in bed (TIB), or 8-hour self-selected TIB; and follow-up focus groups to understand the acceptability of the intervention. Results: Gender (p < 0.001), Hispanic ethnicity (p = 0.023), the care of children (p = 0.014), and chronotype (p = 0.012), predicted the reported ability to spend 8 hours in bed in the afternoon-evening. Participants assigned to the 8-hour self-selected and 8-hour afternoon-evening groups significantly increased their TIB and sleep duration compared to baseline (p < 0.05), while the control group did not. Although spending 8 hours in bed was feasible for the participants during the study, focus group discussions indicated participants would not continue an 8-hour TIB schedule after the study due to family responsibilities and other activities of daily living. Conclusions: Spending 8 hours in bed between successive night shifts, initiated at both a self-selected time and in the afternoon-evening, increased the sleep duration of older shiftworkers, but most would not continue such a schedule on their own. Additional research is needed to find countermeasures for the reduced sleep duration experienced by most shiftworkers that are not only effective, but also compatible with shiftworkers' lifestyles.

Circadian protein expression patterns in healthy young adults.

OBJECTIVES: To explore how the blood plasma proteome fluctuates across the 24-hour day and identify a subset of proteins that show endogenous circadian rhythmicity. METHODS: Plasma samples from 17 healthy adults were collected hourly under controlled conditions designed to unmask endogenous circadian rhythmicity; in a subset of 8 participants, we also collected samples across a day on a typical sleep-wake schedule. A total of 6916 proteins were analyzed from each sample using the SomaScan aptamer-based multiplexed platform. We used differential rhythmicity analysis based on a cosinor model with mixed effects to identify a subset of proteins that showed circadian rhythmicity in their abundance. RESULTS: One thousand and sixty-three (15%) proteins exhibited significant daily rhythmicity. Of those, 431 (6.2%) proteins displayed consistent endogenous circadian rhythms on both a sleep-wake schedule and under controlled conditions: it included both known and novel proteins. When models were fitted with two harmonics, an additional 259 (3.7%) proteins exhibited significant endogenous circadian rhythmicity, indicating that some rhythmic proteins cannot be solely captured by a simple sinusoidal model. Overall, we found that the largest number of proteins had their peak levels in the late afternoon/evening, with another smaller group peaking in the early morning. CONCLUSIONS: This study reveals that hundreds of plasma proteins exhibit endogenous circadian rhythmicity in humans. Future analyses will likely reveal novel physiological pathways regulated by circadian clocks and pave the way for improved diagnosis and treatment for patients with circadian disorders and other pathologies. It will also advance efforts to include knowledge about time-of-day, thereby incorporating circadian medicine into personalized medicine.

Sleep-independent circadian rhythm of aldosterone secretion in healthy young adults.

OBJECTIVE: A diurnal variation in urine output has been described in humans, whereby it is lowest at night. Fluid balance hormones such as vasopressin and aldosterone as well as urine output have a diurnal variation. Although the diurnal variation of vasopressin results in part from a circadian rhythm, the variation in aldosterone has until recently been reported to be due to the sleep/wake cycle. The present study used a specialized protocol to explore whether aldosterone has an underlying circadian rhythm. METHODS: Ten healthy participants (average age 23.1) were enrolled in the 57.3-hour protocol that included an 8-hour baseline sleep episode, 40 hours in constant routine conditions (wakefulness, food and fluid intake, posture, and dim light), and a 9.3-hour recovery sleep. Blood samples for aldosterone were taken every 4 hours. Cosinor analysis was performed on the constant routine data to test the effect of the sleep/wake cycle on overall aldosterone secretion. RESULTS: There was a significant circadian rhythm during the 40-hour constant routine, independent of sleep, with aldosterone higher at the end of the biological night and lower at the end of the biological day. When analyzing data from the entire 57.3-hour protocol and controlling for this circadian rhythm, aldosterone concentration was significantly higher during the recovery night following the 40-hour sleep deprivation compared to the night spent awake. CONCLUSION: We found a significant endogenous circadian rhythm in the secretion of aldosterone, independent of sleep. In addition, as shown previously, there was a significant effect of the sleep/wake cycle on aldosterone secretion.

Evaluation of sleep strategies between night shifts in actual shift workers.

OBJECTIVES: The aim of this observational study was to examine sleep obtained between consecutive night shifts from shift workers in their natural environment. The goal was to identify the various sleep strategies and the timing, duration, regularity, and quality of sleep associated with the strategies. METHODS: Participants (N = 33, 23 women, aged 40 ± 15years) reported their sleep information in daily diaries over 2weeks while working at least one series of consecutive night shifts. Sleep timing, duration, quality, and regularity were calculated for each sleep episode between consecutive night shifts. RESULTS: Based on the reported sleep behavior, shift workers were categorized as either morning, delayed, split- or mixed sleepers. We found significant differences between the groups in timing of sleep, feeling refreshed, and regularity of sleep between consecutive night shifts, whereas duration and subjective soundness of sleep did not show significant differences. CONCLUSIONS: In this sample, four sleep strategies were observed between consecutive night shifts in actual shift workers. These observations may help design future interventions to improve sleep that are individualized to the worker.

Circadian- and wake-dependent influences on face-name memory in healthy men and women over 3weeks of chronic sleep restriction.

OBJECTIVES: Facial recognition is one of the key functions of the human brain, and linking a face to a name is critical in many social and occupational settings. This study assessed circadian- and wake-dependent effects on face-name recognition in healthy adults. METHODS: Thirteen healthy adults (20-70years; 7 F) were studied in a 39-day inpatient protocol that included 3weeks of 28 hours forced desynchrony with sleep restriction (6.5:21.5 hours sleep:wake). Starting 3 hours after scheduled wake, 6 novel face-name pairs were presented every 4 waking hours; recognition was tested 2 hours later. Performance data were averaged across ∼4 hours circadian phase or time-awake bins. RESULTS: Face-name recognition deteriorated with increased time awake (p < .0001) and exhibited significant circadian variation (p < .0001), with worst performance shortly after the core temperature nadir. There was a significant interaction between sex and circadian phase (p = .0177), with women performing significantly better than men at all circadian phases except 60° and 120°. Women exhibited a significantly higher amplitude than men during the third week of forced desynchrony (p < .01). CONCLUSIONS: Like many other aspects of neurobehavioral performance, recalling face-name associations is impacted by both duration of time awake and circadian phase. These results have implications for face recognition testing in medical contexts, such as in testing for dementia, because performance may be impacted by sleep deficiency and the time of testing.

Sleep and circadian disruptors: Unhealthy noise and light levels for hospitalized pediatric patients.

Noise and light levels during hospitalizations can disrupt sleep and circadian health, resulting in worsened health outcomes. This study describes patterns of noise and light for inpatient children undergoing stem cell transplants. Objective meters tracked noise and light levels every minute for 6 months. Median overnight sound was 55 dB (equivalent to conversational speech). There were 3.4 loud noises (>80 dB) per night on average. Children spent 62% of the 24-h cycle in nonoptimal lighting, with daytime light dimmer than recommended 98% of the time. Over the 6-month period, the lowest overnight noise level recorded exceeded World Health Organization recommendations for sleep, with frequent spikes into ranges known to cause wakings. During the day, children were rarely exposed to light sufficient to preserve healthy circadian rhythms. Hospitals should address systematic environmental and workflow disruptors to improve the sleep and circadian health of patients, particularly those already at elevated risk for health morbidities.

Interventions to improve the sleep of nurses: A systematic review.

Nurses are at a high risk for short sleep duration and poor sleep quality due to irregular work schedules and high occupational stress. Considering the effect of nurses' sleep on the safety and health of themselves and their patients, it is important to promote healthy sleep for nurses. We sought to synthesize the published experimental and quasi-experimental studies that address interventions to improve sleep in nurses. A systematic search was conducted for studies published in English up until May 15, 2023, using the databases PubMed, CINAHL, Academic Search Ultimate, and PsycINFO. In total, 38 articles were included, covering 22 experimental and 16 quasi-experimental studies with sample sizes ranging from 9 to 207. Studies were assessed using the Cochrane Risk of Bias tool and considered as low to medium quality. Thirty-six of the 38 studies reported positive findings for at least one sleep outcome. Intervention types included aroma therapy, dietary supplements, cognitive behavioral therapy, light therapy, mind-body therapy, sleep education, exercise, napping, shift schedule modification, and multicomponent intervention, all of which showed moderate effectiveness in promoting sleep outcomes of nurses. Comparing and contrasting studies on specific interventions for improving sleep in nurses is sparse and often equivocal. With the variations of research methodology and outcome measures, it is difficult to make a conclusion about each intervention's effectiveness on specific sleep outcomes. Additional high-quality research, including randomized controlled trials, is needed to evaluate strategies for improving sleep in this unique, safety-sensitive occupational group.

Eating during the biological night is associated with nausea.

OBJECTIVES: This study assessed whether there was a time-of-day effect on nausea reports in participants during studies employing circadian protocols. METHODS: Visual-analog-scales of nausea ratings were recorded from 34 participants (18-70years; 18 women) during forced desynchrony studies, where meals were scheduled at different circadian phases. Subjective nausea reports from a further 81 participants (18-35years; 36 women) were recorded during constant routine studies, where they ate identical isocaloric hourly snacks for 36-40 hours. RESULTS: Feelings of nausea varied by circadian phase in the forced desynchrony studies, peaking during the biological night. Nausea during the constant routine was reported by 27% of participants, commencing 2.9 ± 5.2 hours after the midpoint of usual sleep timing, but was never reported to start in the evening (4-9 PM). CONCLUSIONS: Nausea occurred more often during the biological night and early morning hours. This timing is relevant to overnight and early morning shift workers and suggests that a strategy to counteract that is to pay careful attention to meal timing.

The Timing of the Melatonin Onset and Phase Angle to Sleep Onset in Older Adults after Uncontrolled vs. Controlled Lighting Conditions.

The main aim of this study was to explore how melatonin onset timing and phase angle to bedtime in healthy older adults are impacted by prior light exposure. A total of 13 healthy older (ages 56-74) individuals were studied on two successive evenings. Prior to the first evening, the participants were in self-selected lighting conditions for the first 4-6 h of the day and then were in dim light (3 lux) until their scheduled bedtime. On the second day, individuals from Project A remained in the dim lighting conditions throughout the entire day but those in Project B were in more typical indoor lighting (~90 lux) throughout the day. On both evenings, hourly blood samples were collected and assayed for melatonin, and melatonin onset timing and phase angle to sleep onset was determined. Overall, melatonin onset was earlier and the phase angle was larger on Night 1 than on Night 2. In Project A there was no significant difference between melatonin onset on night 1 vs. night 2. However, in Project B melatonin onset was significantly later on Night 2 (in typical indoor lighting) than on Night 1 (in dim lighting). Our results suggest that in older people, uncontrolled bright light early in the day did not impact the timing of dim light melatonin onset (DLMO) when assessed later that same evening. However, in older adults, exposure to ordinary room light during melatonin phase assessment appeared to suppress melatonin, leading to a later observed time of melatonin onset, as has been reported previously for young adults.

Age-related changes in circadian regulation of the human plasma lipidome.

Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in 24 healthy individuals (9 females; mean ± SD age: 40.9 ± 18.2 years) including 12 younger (4 females, 23.5 ± 3.9 years) and 12 middle-aged older, (5 females, 58.3 ± 4.2 years) individuals every 3 h throughout a 27-h constant routine (CR) protocol, which allows separating evoked changes from endogenously generated oscillations in physiology. Cosinor regression shows circadian rhythmicity in 25% of lipids in both groups. On average, the older group has a ~14% lower amplitude and a ~2.1 h earlier acrophase of the lipid circadian rhythms (both, p ≤ 0.001). Additionally, more rhythmic circadian lipids have a significant linear component in addition to the sinusoidal across the 27-h CR in the older group (44/56) compared to the younger group (18/58, p < 0.0001). Results from individual-level data are consistent with group-average results. Results indicate that prevalence of endogenous circadian rhythms of the human plasma lipidome is preserved with healthy aging into middle-age, but significant changes in rhythmicity include a reduction in amplitude, earlier acrophase, and an altered temporal relationship between central and lipid rhythms.

The influence of a permanent double-shift school start time on adolescent sleep and chronotype across different age groups.

The main objective of this study was to explore the differences in sleep habits and chronotype across different age groups in Mexican adolescents attending a permanent double-shift school system. This cross-sectional study consisted of 1,969 (1,084 girls) students from public elementary, secondary, and high schools, as well as undergraduate university students from Mexico. Age range was 10-22 [15.33 ± 3.28 (mean ± SD)] years, 988 morning shift and 981 afternoon shift students. Questions regarding usual self-reported bedtime and rise time were collected, and from that, estimates for time in bed, midpoint of sleep, social jetlag, and chronotype were evaluated. Afternoon shift students reported later rise times, bedtimes, midpoint of sleep, and longer time in bed on school days than morning shift students, as well as less social jetlag. Overall, afternoon shift students reported a later chronotype than morning shift students. Peak lateness of chronotype in afternoon shift students was at age 15, with girls peaking at age 14 and boys at age 15. Meanwhile, morning shift students reported peak lateness of chronotype around age 20. In this study, adolescents from different age ranges attending an extremely delayed school start time reported adequate sleep compared with adolescents attending a fixed morning school start time. In addition, the analysis presented in this study seems to suggest that the peak of late chronotype may be influenced by school start times.

Desynchronizing the sleep---wake cycle from circadian timing to assess their separate contributions to physiology and behaviour and to estimate intrinsic circadian period.

Circadian clocks drive cyclic variations in many aspects of physiology, but some daily variations are evoked by periodic changes in the environment or sleep-wake state and associated behaviors, such as changes in posture, light levels, fasting or eating, rest or activity and social interactions; thus, it is often important to quantify the relative contributions of these factors. Yet, circadian rhythms and these evoked effects cannot be separated under typical 24-h day conditions, because circadian phase and the length of time awake or asleep co-vary. Nathaniel Kleitman's forced desynchrony (FD) protocol was designed to assess endogenous circadian rhythmicity and to separate circadian from evoked components of daily rhythms in multiple parameters. Under FD protocol conditions, light intensity is kept low to minimize its impact on the circadian pacemaker, and participants have sleep-wake state and associated behaviors scheduled to an imposed non-24-h cycle. The period of this imposed cycle, Τ, is chosen so that the circadian pacemaker cannot entrain to it and therefore continues to oscillate at its intrinsic period (τ, ~24.15 h), ensuring circadian components are separated from evoked components of daily rhythms. Here we provide detailed instructions and troubleshooting techniques on how to design, implement and analyze the data from an FD protocol. We provide two procedures: one with general guidance for designing an FD study and another with more precise instructions for replicating one of our previous FD studies. We discuss estimating circadian parameters and quantifying the separate contributions of circadian rhythmicity and the sleep-wake cycle, including statistical analysis procedures and an R package for conducting the non-orthogonal spectral analysis method that enables an accurate estimation of period, amplitude and phase.

Circadian Rhythm Sleep-Wake Disorders in Older Adults.

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.

High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults.

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 (age >55, 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 circadian disruption on a high-fat diet impairs glucose tolerance.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of chronic sleep restriction on sleep continuity, sleep structure, and neurobehavioral performance.

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 ±â€…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 ±â€…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).

Chronic Sleep Restriction While Minimizing Circadian Disruption Does Not Adversely Affect Glucose Tolerance.

Insufficient sleep, which has been shown to adversely affect metabolism, is generally associated with prolonged exposure to artificial light at night, a known circadian disruptor. There is growing evidence suggesting that circadian disruption adversely affects metabolism, yet few studies have attempted to evaluate the adverse metabolic effects of insufficient sleep while controlling for circadian disruption. We assessed postprandial glucose and insulin responses to a standard breakfast meal in healthy adults (n = 9) who underwent 3 weeks of chronic sleep restriction (CSR) in a 37-day inpatient study while minimizing circadian disruption by maintaining the same duration of light exposure each study day. We compared these results to findings from an earlier inpatient study which used a forced desynchrony (FD) protocol to assess the influence of 3 weeks of CSR combined with recurrent circadian disruption (RCD) on glycemic control in healthy adults (n = 21). CSR combined with RCD resulted in significantly elevated postprandial plasma glucose levels (p < 0.0001), while CSR with minimized circadian disruption had no adverse glycemic effects after 3 weeks of exposure (EXP). These results suggest that one mechanism by which sleep restriction impacts metabolism may be via concurrent circadian disruption.

Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 1: Basic and Translational Aspects.

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.