Analysis of dynamic, bidirectional associations in older adult physical activity and sleep quality.

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.

Organisational characteristics associated with shift work practices and potential opportunities for intervention: findings from a Canadian study.

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 work's 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.

Measuring Physical Activity in Older Adults Using MotionWatch 8 Actigraphy: How Many Days are Needed?

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.

Phenotyping food entrainment: motion sensors and telemetry are equivalent.

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 approximately 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.

Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- 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.

Food anticipation in Bmal1-/- and AAV-Bmal1 rescued mice: a reply to Fuller et al.

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.

The dorsomedial hypothalamic nucleus is not necessary for the expression of circadian food-anticipatory activity in rats.

Restricted daytime feeding generates food-anticipatory activity (FAA) by entrainment of a circadian pacemaker separate from the light-entrainable pacemaker located in the SCN. The dorsomedial hypothalamic nucleus (DMH) has been proposed as the site of food-entrainable oscillators critical for the expression of FAA, but another study found no effects of complete DMH ablation on FAA. To account for these different results, the authors examined methodological factors, including (1) cage configuration and feeding method and (2) use of social cues. Intact and DMH-ablated rats were maintained on one 4-h daily meal in the middle of the light period, using caging and feeding methods matching those of Gooley et al. (2006). Rats with partial or complete DMH ablation were less nocturnal during ad lib food access but exhibited normal FAA during restricted feeding, as quantified by FAA magnitude, ratios, latency to appearance, duration, and precision. To evaluate the use of social cues, intact rats naive to restricted-feeding schedules were food deprived for 72 h on 4 tests. Daytime activity increased during food deprivation, but the magnitude and waveform of this activity was not influenced by the presence of food-entrained rats exhibiting robust FAA in adjacent cages. Thus, hungry intact rats do not use social cues to anticipate a daily mealtime, suggesting that DMH-ablated rats do not anticipate meals by reacting to sounds from food-entrained intact rats in adjacent cabinets. These results confirm our previous finding that the DMH is not critical for normal expression of FAA in rats, and this observation is extended to food restriction methodologies used by other labs. The methodological differences that do underlie discrepant results remain unresolved, as does the location of food-entrainable oscillators, input pathways, and output pathways critical for FAA.

Buying time: a proof-of-concept randomized controlled trial to improve sleep quality and cognitive function among older adults with mild cognitive impairment.

BACKGROUND: 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. METHODS/DESIGN: 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). DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02926157 . Registered on 6 October 2016.

Cross-Sectional Relationships of Physical Activity and Sedentary Behavior With Cognitive Function in Older Adults With Probable Mild Cognitive Impairment.

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 <26/30) and participants without MCI (scores of ≥26/30). Cognitive function was indexed using the Alzheimer Disease Assessment Scale-Cognitive-Plus (ADAS-Cog Plus). Physical activity and sedentary behavior were compared based on probable MCI status, and relationships of ADAS-Cog Plus with PA and sedentary behavior were examined by probable MCI status. 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 (ß = -.022 and ß = .012, respectively) but not in participants with probable MCI (ß < .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.

Differential effects of constant light on circadian clock resetting by photic and nonphotic stimuli in Syrian hamsters.

Circadian rhythms in Syrian hamsters can be phase shifted by behavioral arousal during the usual rest phase of the circadian rest-activity cycle. Phase shifts can be greatly potentiated by exposing the animals to constant light for 1 or 2 cycles. This could reflect a change in a specific nonphotic input pathway to the suprachiasmatic nucleus (SCN) circadian pacemaker, or it could be caused by a change in the amplitude of the pacemaker. If the latter, then phase shifts to any stimulus, including those activating the photic input pathway, should be potentiated. This hypothesis was tested by measuring phase shifts induced by microinjections of NMDA (500 nl, 10 mM) into the SCN area of hamsters exposed to constant light or dark for 2 days. NMDA induced significant phase delay shifts that mimicked those induced by light exposure early in the night. The magnitude of these shifts did not differ by prior lighting condition. Shifts induced by NMDA (200 nl, 10 mM) microinjections on day 3 and 13 of LL also did not differ. Phase shifts induced by a nonphotic stimulus (3 h of running stimulated by confinement to a novel wheel) were significantly potentiated by 2 days of exposure to constant light. These results indicate that exposure to constant light for 2 circadian cycles differentially affects phase resetting responses to photic and nonphotic inputs to the circadian pacemaker, suggesting that potentiation of shifts to nonphotic stimuli reflect changes in a nonphotic input pathway rather than in an amplitude dimension of the circadian pacemaker.

Measuring sleep quality in older adults: a comparison using subjective and objective methods.

Sleep quality decreases with aging and thus sleep complaints are prevalent in older adults, particularly for those with cognitive impairment and dementia. For older adults, emerging evidence suggests poor sleep quality increases risk of developing cognitive impairment and dementia. Given the aging population-and the impending economic burden associated with increasing numbers of dementia patients-there is pressing need to improve sleep quality among older adults. As such, research efforts have increased focus on investigating the association between age-related sleep changes and cognitive decline in older adults. Sleep quality is a complex construct to evaluate empirically, and yet the Pittsburg Sleep Quality Index (PSQI) is commonly used in studies as their only measure of sleep quality. Furthermore, the PSQI may not be the best sleep quality measure for older adults, due to its reliance on the cognitive capacity to reflect on the past month. Further study is needed to determine the PSQI's validity among older adults. Thus, the current study examined sleep quality for 78 community dwelling adults 55+ to determine the PSQI's predictive validity for objective sleep quality (as measured by actigraphy). We compared two subjective measures of sleep quality-the PSQI and Consensus Sleep Diary (CSD)-with actigraphy (MotionWatch 8©; camntech). Our results suggest perceived sleep quality is quite different from objective reality, at least for adults 55+. Importantly, we show this difference is unrelated to age, gender, education, or cognitive status (assessed using standard screens). Previous studies have shown the PSQI to be a valuable tool for assessing subjective sleep quality; however, our findings indicate for older adults the PSQI should not be used as a substitute for actigraphy, or vice versa. Hence, we conclude best practice is to include both subjective and objective measures when examining sleep quality in older adults (i.e., the PSQI, CSD, and actigraphy).

Measuring physical activity in older adults: calibrating cut-points for the MotionWatch 8(©).

Given the world's aging population, the staggering economic impact of dementia, the lack of effective treatments, and the fact a cure for dementia is likely many years away - there is an urgent need to develop interventions to prevent or at least delay dementia's progression. Thus, lifestyle approaches to promote healthy aging are an important line of scientific inquiry. Good sleep quality and physical activity (PA) are pillars of healthy aging, and as such, are an increasing focus for intervention studies aimed at promoting health and cognitive function in older adults. However, PA and sleep quality are difficult constructs to evaluate empirically. Wrist-worn actigraphy (WWA) is currently accepted as a valid objective measure of sleep quality. The MotionWatch 8(©) (MW8) is the latest WWA, replacing the discontinued Actiwatch 4 and Actiwatch 7. In the current study, concurrent measurement of WWA and indirect calorimetry was performed during 10 different activities of daily living for 23 healthy older adults (aged 57-80 years) to determine cut-points for sedentary and moderate-vigorous PA - using receiver operating characteristic curves - with the cut-point for light activity being the boundaries between sedentary and moderate to vigorous PA. In addition, simultaneous multi-unit reliability was determined for the MW8 using inter-class correlations. The current study is the first to validate MW8 activity count cut-points - for sedentary, light, and moderate to vigorous PA - specifically for use with healthy older adults. These cut-points provide important context for better interpretation of MW8 activity counts, and a greater understanding of what these counts mean in terms of PA. Hence, our results validate another level of analysis for researchers using the MW8 in studies aiming to examine PA and sleep quality concurrently in older adults.

Buying time: a rationale for examining the use of circadian rhythm and sleep interventions to delay progression of mild cognitive impairment to Alzheimer's disease.

As of 2010, the worldwide economic impact of dementia was estimated at $604 billion USD; and without discovery of a cure or effective interventions to delay disease progression, dementia's annual global economic impact is expected to surpass $1 trillion USD as early as 2030. Alzheimer's disease (AD) is the leading cause of dementia accounting for over 75% of all cases. Toxic accumulation of amyloid beta (Aß), either by overproduction or some clearance failure, is thought to be an underlying mechanism of the neuronal cell death characteristic of AD-though this amyloid hypothesis has been increasingly challenged in recent years. A compelling alternative hypothesis points to chronic neuroinflammation as a common root in late-life degenerative diseases including AD. Apolipoprotein-E (APOE) genotype is the strongest genetic risk factor for AD: APOE-ε4 is proinflammatory and individuals with this genotype accumulate more Aß, are at high risk of developing AD, and almost half of all AD patients have at least one ε4 allele. Recent studies suggest a bidirectional relationship exists between sleep and AD pathology. Sleep may play an important role in Aß clearance, and getting good quality sleep vs. poor quality sleep might reduce the AD risk associated with neuroinflammation and the ε4 allele. Taken together, these findings are particularly important given the sleep disruptions commonly associated with AD and the increased burden disrupted sleep poses for AD caregivers. The current review aims to: (1) identify individuals at high risk for dementia who may benefit most from sleep interventions; (2) explore the role poor sleep quality plays in exacerbating AD type dementia; (3) examine the science of sleep interventions to date; and (4) provide a road map in pursuit of comprehensive sleep interventions, specifically targeted to promote cognitive function and delay progression of dementia.

Scheduled daily mating induces circadian anticipatory activity rhythms in the male rat.

Daily schedules of limited access to food, palatable high calorie snacks, water and salt can induce circadian rhythms of anticipatory locomotor activity in rats and mice. All of these stimuli are rewarding, but whether anticipation can be induced by neural correlates of reward independent of metabolic perturbations associated with manipulations of food and hydration is unclear. Three experiments were conducted to determine whether mating, a non-ingestive behavior that is potently rewarding, can induce circadian anticipatory activity rhythms in male rats provided scheduled daily access to steroid-primed estrous female rats. In Experiment 1, rats anticipated access to estrous females in the mid-light period, but also exhibited post-coital eating and running. In Experiment 2, post-coital eating and running were prevented and only a minority of rats exhibited anticipation. Rats allowed to see and smell estrous females showed no anticipation. In both experiments, all rats exhibited sustained behavioral arousal and multiple mounts and intromissions during every session, but ejaculated only every 2-3 days. In Experiment 3, the rats were given more time with individual females, late at night for 28 days, and then in the midday for 28 days. Ejaculation rates increased and anticipation was robust to night sessions and significant although weaker to day sessions. The anticipation rhythm persisted during 3 days of constant dark without mating. During anticipation of nocturnal mating, the rats exhibited a significant preference for a tube to the mating cage over a tube to a locked cage with mating cage litter. This apparent place preference was absent during anticipation of midday mating, which may reflect a daily rhythm of sexual reward. The results establish mating as a reward stimulus capable of inducing circadian rhythms of anticipatory behavior in the male rat, and reveal a critical role for ejaculation, a modulatory role for time of day, and a potential confound role for uncontrolled food intake.

Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats.

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.

Comment on "Differential rescue of light- and food-entrainable circadian rhythms".

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.