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Evidence suggests sleep and physical activity (PA) are associated with each other and dementia risk. Thus, identifying reliable methods to quantify sleep and PA concurrently in older adults is important. The MotionWatch 8© (MW8) wrist-worn actigraph provides reliable estimates of sleep quality via 14 days of measurement; however, the number of days needed to monitor PA by MW8 for reliable estimates is unknown. Thus, we investigated the number of days of MW8 wear required to assess PA in older adults. Ninety-five adults aged > 55 years wore MW8 for ≥ 14 days. Spearman-Brown analyses indicated the number of monitoring days needed for an ICC = 0.95 was 6–7 days for sedentary activity, 9–10 days for light activity, and 7–8 days for moderate-to-vigorous PA. These results indicate 14 days of MW8 monitoring provides reliable estimates for both sleep and PA. Thus, MW8 is ideal for future investigations requiring concurrent measures of both sleep quality and PA.

Current evidence suggests that good quality sleep is associated with preserved cognitive function and reduced dementia risk in older adults. Sleep complaints are especially common among older adults with mild cognitive impairment (MCI), and this may contribute to their increased risk for progression to dementia. Thus, improving their sleep may be important for maintaining their cognitive health. Chronotherapy is a set of intervention strategies that can improve sleep quality through strengthening the entrainment of the biological clock to the solar light-dark cycle, and includes strategies such as (1) bright light therapy (BLT); (2) physical activity (PA); and (3) good sleep hygiene. Of these strategies, BLT is the most potent and is based on providing individualized timing to entrain circadian rhythms. Thus, a personalized chronotherapy intervention of individually timed BLT and individually tailored PA promotion, in conjunction with general sleep hygiene education may promote older adult sleep quality. We therefore aim to carry out a proof-of-concept randomized controlled trial (RCT) to examine the efficacy of such a personalized chronotherapy intervention to improve sleep quality among older adults with MCI. This was a 24-week RCT of a personalized chronotherapy intervention aimed to primarily improve sleep quality as measured by the MotionWatch8©. Participants in the personalized chronotherapy group (INT) will receive four once-weekly, general sleep hygiene education classes, followed by 20 weeks of (1) individually timed BLT and (2) bi-weekly, individually tailored PA counseling phone calls in conjunction with receiving a consumer-available PA tracker—the Fitbit® Flex™. Ninety-six adults (aged 65–85 years) classified as having MCI (i.e., Mini-Mental State Exam (MMSE) ≥ 24; Montreal Cognitive Assessment (MoCA) ≤ 26; without dementia or significant functional impairment) will be randomized to either INT or a waitlist control group (CON). The results of this trial will help determine if a personalized chronotherapy intervention that includes individually timed BLT and individually tailored PA promotion, along with general sleep hygiene education can promote sleep quality among older adults at increased risk for dementia. Our results will help inform best practices for promoting sleep quality among older adults with MCI. ClinicalTrials.gov , NCT02926157 . Registered on 6 October 2016.

Poor sleep is common among older adults with Mild Cognitive Impairment (MCI) and may contribute to their increased risk for dementia. Chronotherapy is a set of intervention strategies which can improve sleep quality by strengthening the entrainment of the biological clock to the solar light-dark cycle, and includes strategies such as: 1) bright light therapy (BLT); 2) physical activity (PA); and 3) good sleep hygiene. Thus, in this 24-week randomized controlled trial (RCT; NCT02926157), we aimed to examine the efficacy of a multimodal, personalized chronotherapy intervention to improve sleep quality among older adults with MCI. Ninety-six older adults (65+ years) with MCI were randomized to either: 1) a multimodal personalized chronotherapy group (INT); or 2) a waitlist-plus-education control group (CON). Participants allocated to the INT received four once-weekly, general sleep hygiene education classes, followed by 20 weeks of 1) individually-timed BLT; and 2) bi-weekly, individually-tailored PA counselling in conjunction with receiving a consumer-available PA tracker (Fitbit® FlexTM). We found a significant group x time interaction for objectively measured sleep fragmentation (5.01; p< 0.01) and also for Pittsburgh Sleep Quality Index (PSQI) score (p= 0.03), such that the INT: 1) maintained sleep fragmentation while CON worsened at 12 weeks (p< 0.01); and 2) had improved PSQI score compared to CON at both 12 weeks (p< 0.01) and 24 weeks (p= 0.04). Our results provide novel evidence that a multimodal personalized chronotherapy approach may promote both objective and subjective aspects of sleep quality in older adults with MCI.

Background Mild cognitive impairment (MCI) represents a transition between normal cognitive aging and dementia and may represent a critical time frame for promoting cognitive health through behavioral strategies. Current evidence suggests that physical activity (PA) and sedentary behavior are important for cognition. However, it is unclear whether there are differences in PA and sedentary behavior between people with probable MCI and people without MCI or whether the relationships of PA and sedentary behavior with cognitive function differ by MCI status. Objective The aims of this study were to examine differences in PA and sedentary behavior between people with probable MCI and people without MCI and whether associations of PA and sedentary behavior with cognitive function differed by MCI status. Design This was a cross-sectional study. Methods Physical activity and sedentary behavior in adults dwelling in the community (N = 151; at least 55 years old) were measured using a wrist-worn actigraphy unit. The Montreal Cognitive Assessment was used to categorize participants with probable MCI (scores of Results Participants with probable MCI (n = 82) had lower PA and higher sedentary behavior than participants without MCI (n = 69). Higher PA and lower sedentary behavior were associated with better ADAS-Cog Plus performance in participants without MCI (β = −.022 and β = .012, respectively) but not in participants with probable MCI (β < .001 for both). Limitations This study was cross-sectional and therefore could not establish whether conversion to MCI attenuated the relationships of PA and sedentary behavior with cognitive function. The diagnosis of MCI was not confirmed with a physician; therefore, this study could not conclude how many of the participants categorized as having probable MCI would actually have been diagnosed with MCI by a physician. Conclusions Participants with probable MCI were less active and more sedentary. The relationships of these behaviors with cognitive function differed by MCI status; associations were found only in participants without MCI.

Introduction Shift work is a common working arrangement with wide-ranging implications for worker health. Organisational determinants of shift work practices are not well characterised; such information could be used to guide evidence-based research and best practices to mitigate shift work9s negative effects. This exploratory study aimed to describe and assess organisational-level determinants of shift work practices thought to affect health, across a range of industry sectors. Methods Data on organisational characteristics, shift work scheduling, provision of shift work education materials/training to employees and night-time lighting policies in the workplace were collected during phone interviews with organisations across the Canadian province of British Columbia. Relationships between organisational characteristics and shift work practices were assessed using multivariable logistic regression models. Results The study sample included 88 participating organisations, representing 30 700 shift workers. Long-duration shifts, provision of shift work education materials/training to employees and night-time lighting policies were reported by approximately one-third of participating organisations. Odds of long-duration shifts increased in larger workplaces and by industry. Odds of providing shift work education materials/training increased in larger workplaces, in organisations reporting concern for shift worker health and in organisations without seasonal changes in shift work. Odds of night-time lighting policies in the workplace increased in organisations reporting previous workplace accidents or incidents that occurred during non-daytime hours, site maintenance needs and client service or care needs. Conclusions This study points to organisational determinants of shift work practices that could be useful for targeting research and workplace interventions. Results should be interpreted as preliminary in an emerging body of literature on shift work and health.

Sleep quality and physical activity (PA) appear to be interrelated; thus, by promoting one behaviour, it may be possible to improve the other in older adults. Examination of the within-person day-to-day variation in PA and sleep quality could potentially elucidate the directionality of the association of these behaviours. We measured sleep quality (i.e. fragmentation, efficiency, duration and latency) and moderate-to-vigorous PA using the MotionWatch8© over 14 consecutive days and nights in community-dwelling adults (n = 152; age range 53-101 years). Multilevel modelling estimated within-subject autoregressive and cross-lagged effects and between-subject associations between PA and sleep quality. On days when individuals engaged in a high amount of PA on one day (relative to their averages), they were more likely to engage in a high amount of PA on the next day (estimate, 0.19; 95% CI, 0.14, 0.24). Nights in which individuals had a long sleep latency were followed by nights in which they also had a long sleep latency (estimate, 0.09; 95% CI, 0.03, 0.14). In contrast, nights in which individuals slept for a long period of time were followed by nights in which they slept relatively less than their averages (estimate, -0.09; 95% CI, -0.13, -0.04). When individuals engaged in a large amount of PA during the day, they tended to sleep longer that following night (estimate, 0.01; 95% CI, 0.001, 0.02). All other associations between PA and sleep quality were not significant. Increasing PA therefore might increase sleep duration in older adults.

Some procedures for stimulating arousal in the usual daily rest period (e.g., gentle handling, novel wheel-induced running) can phase shift circadian rhythms in Syrian hamsters, while other arousal procedures are ineffective (inescapable stress, caffeine, modafinil). The dorsal and median raphe nuclei (DRN, MnR) have been implicated in clock resetting by arousal and, in rats and mice, exhibit strong regionally specific responses to inescapable stress and anxiogenic drugs. To examine a possible role for the midbrain raphe nuclei in the differential effects of arousal procedures on circadian rhythms, hamsters were aroused for 3 h in the mid-rest period by confinement to a novel running wheel, gentle handling (with minimal activity) or physical restraint (with intermittent, loud compressed air stimulation) and sacrificed immediately thereafter. Regional expression of c-fos and tryptophan hydroxylase (TrpOH) were quantified immunocytochemically in the DRN, MnR and locus coeruleus (LC). Neither gentle handling nor wheel running had a large impact on c-fos expression in these areas, although the manipulations were associated with a small increase in c-Fos in TrpOH-like and TrpOH-negative cells, respectively, in the caudal interfascicular DRN region. By contrast, restraint stress significantly increased c-Fos in both TrpOH-like and TrpOH-negative cells in the rostral DRN and LC. c-Fos-positive cells in the DRN did not express tyrosine hydroxylase. These results reveal regionally specific monoaminergic correlates of arousal-induced circadian clock resetting, and suggest a hypothesis that strong activation of some DRN and LC neurons by inescapable stress may oppose clock resetting in response to arousal during the daily sleep period. More generally, these results complement evidence from other rodent species for functional topographic organization of the DRN.

Rats can anticipate a daily meal by entrainment of a circadian timekeeping mechanism that is anatomically separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nucleus. The dorsomedial nucleus of the hypothalamus (DMH) has been claimed to be critical for the expression of circadian rhythms of food anticipatory activity, but efforts to confirm this finding have so far failed. Failure to confirm that DMH ablation disrupts or eliminates food anticipatory rhythms has been attributed to the use of overhead motion sensors rather than telemetry to measure locomotor activity. To examine the relationship between motion sensor and telemetric measures of locomotor activity, transponders were implanted into the peritoneal cavity of adult male rats, and activity was recorded continuously by both telemetry and infrared motion sensors. Activity counts were ~4 fold higher as detected by telemetry, but normalized activity patterns were virtually identical for the two measures during ad-lib food access, 4 h/day food restriction and total food deprivation after food restriction. Overhead motion sensors and telemetry are equivalent measures of food anticipatory activity in rats. Telemetry is an effective tool for continuous recording of body temperature but has no advantages over infrared motion sensors for measuring food anticipatory activity rhythms.

When food is plentiful, circadian rhythms of animals are powerfully entrained by the light-dark cycle. However, if animals have access to food only during their normal sleep cycle, they will shift most of their circadian rhythms to match the food availability. We studied the basis for entrainment of circadian rhythms by food and light in mice with targeted disruption of the clock gene Bmal1 , which lack circadian rhythmicity. Injection of a viral vector containing the Bmal1 gene into the suprachiasmatic nuclei of the hypothalamus restored light-entrainable, but not food-entrainable, circadian rhythms. In contrast, restoration of the Bmal1 gene only in the dorsomedial hypothalamic nucleus restored the ability of animals to entrain to food but not to light. These results demonstrate that the dorsomedial hypothalamus contains a Bmal1 -based oscillator that can drive food entrainment of circadian rhythms.

Rats can anticipate a fixed daily mealtime by entrainment of a circadian timekeeping mechanism anatomically separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nucleus. Neural substrates of this food-entrainable circadian system have not yet been fully elucidated. A role for the thalamic paraventricular nucleus (PVT) is suggested by observations that scheduled feeding synchronizes daily rhythms of glucose utilization and immediate early gene and circadian clock gene expression in this area. One study has reported absence of food anticipatory circadian activity rhythms in rats with PVT ablations. To determine whether this effect extends to other behavioral measures of food anticipation, rats received large radiofrequency lesions aimed at the PVT and were maintained on a 3-h meal provided each day 6 h after lights-on. Rats with unambiguously complete PVT ablation exhibited increased total daily activity, a change in the waveform of the nocturnal activity rhythm, but no change in the amplitude, duration, latency to appearance or persistence during total food deprivation of food anticipatory activity measured by activity at or near a food bin accessible via a small window in the recording cage. These results indicate that, while the PVT may modulate light-entrainable rhythms, it is not a critical input, oscillator or output component of the circadian system by which rats behaviorally anticipate a daily mealtime.

Circadian rhythms of behavior in rodents are regulated by a system of circadian oscillators, including a master light-entrainable pacemaker in the suprachiasmatic nucleus that mediates synchrony to the day-night cycle, and food-entrainable oscillators located elsewhere that generate rhythms of food-anticipatory activity (FAA) synchronized to daily feeding schedules. Despite progress in elucidating neural and molecular mechanisms of circadian oscillators, localization of food-entrainable oscillators driving FAA remains an enduring problem. Recent evidence suggests that the dorsomedial hypothalamic nucleus (DMH) may function as a final common output for behavioral rhythms and may be critical for the expression of FAA (Gooley JJ, Schomer A, and Saper CB. Nat Neurosci 9: 398–407, 2006). To determine whether the reported loss of FAA by DMH lesions is specific to one behavioral measure or generalizes to other measures, rats received large radiofrequency lesions aimed at the DMH and were recorded in cages with movement sensors. Total and partial DMH ablation was associated with a significant attenuation of light-dark-entrained activity rhythms during ad libitum food access, because of a selective reduction in nocturnal activity. When food was restricted to a single 3-h daily meal in the middle of the lights-on period, all DMH and intact rats exhibited significant FAA. The rhythm of FAA persisted during a 48-h food deprivation test and reappeared during a 72-h deprivation test after ad libitum food access. The DMH is not the site of oscillators or entrainment pathways necessary for all manifestations of FAA, but may participate on the output side of this circadian function.

To determine whether sleep deprivation (SD) affects the response of circadian rhythms to light, hamsters were forced to walk on a slowly rotating treadmill for 6 or 24 h, ending early in the night, with or without a light pulse during the last 30 min. SD alone did not produce a significant phase shift. Light pulses (300 and 50 lx) alone induced significant delay shifts (55 and 35 min, respectively). Twenty-four hours SD significantly attenuated the delay to brighter light and 6 h SD significantly attenuated the delay to moderate light. Sleep loss or attendant low-intensity continuous activity appear to modulate the response of the hamster circadian system to light.

The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b)) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b) rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b) rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.

Evidence that circadian food-anticipatory activity and temperature rhythms are absent in Bmal1 knockout mice and rescued by restoration of Bmal1 expression selectively in the dorsomedial hypothalamus was published in 2008 by Fuller et al and critiqued in 2009 by Mistlberger et al. Fuller et al have responded to the critique with new information. Here we update our critique in the light of this new information. We also identify and correct factual and conceptual errors in the Fuller et al response. We conclude that the original results of Fuller et al remain inconclusive and fail to clarify the role of Bmal1 or the dorsomedial hypothalamus in the generation of food-entrainable rhythms in mice.

Daily feeding schedules generate food anticipatory rhythms of behavior and physiology that exhibit canonical properties of circadian clock control. The molecular mechanisms and location of food-entrainable circadian oscillators hypothesized to control food anticipatory rhythms are unknown. In 2008, Fuller et al reported that food-entrainable circadian rhythms are absent in mice bearing a null mutation of the circadian clock gene Bmal1 and that these rhythms can be rescued by virally-mediated restoration of Bmal1 expression in the dorsomedial nucleus of the hypothalamus (DMH) but not in the suprachiasmatic nucleus (site of the master light-entrainable circadian pacemaker). These results, taken together with controversial DMH lesion results published by the same laboratory, appear to establish the DMH as the site of a Bmal1-dependent circadian mechanism necessary and sufficient for food anticipatory rhythms. However, careful examination of the manuscript reveals numerous weaknesses in the evidence as presented. These problems are grouped as follows and elaborated in detail: 1. data management issues (apparent misalignments of plotted data), 2. failure of evidence to support the major conclusions, and 3. missing data and methodological details. The Fuller et al results are therefore considered inconclusive, and fail to clarify the role of either the DMH or Bmal1 in the expression of food-entrainable circadian rhythms in rodents.

Fuller et al . (Reports, 23 May 2008, p. 1074) reported that the dorsomedial hypothalamus contains a Bmal1 -based oscillator that can drive food-entrained circadian rhythms. We report that mice bearing a null mutation of Bmal1 exhibit normal food-anticipatory circadian rhythms. Lack of food anticipation in Bmal1 – / – mice reported by Fuller et al . may reflect morbidity due to weight loss, thus raising questions about their conclusions.