24-h Activity Rhythm Research Articles

Sleep and 24-H Activity Rhythms and the Risk of Stroke: A Prospective Cohort Study

Introduction: Short and long self-reported sleep durations are associated with a higher risk of stroke, but the association between objective estimates of sleep and 24-h activity rhythms is less clear. We studied the association of actigraphy-estimated sleep and 24-h activity rhythms with the risk of stroke in a population-based cohort of middle-aged and elderly. Methods: We included 1,718 stroke-free participants (mean age 62.2 ± 9.3 years, 55.1% women) from the prospective, population-based Rotterdam Study. Actigraphy-estimated sleep (total sleep time, sleep efficiency, sleep onset latency, and wake after sleep onset) and 24-h activity rhythms (interdaily stability, intradaily variability, and onset of the least active 5 h) were measured during a median of 7 days (Q1–Q3: 6–7 days). The association of sleep and 24-h activity rhythms with risk of stroke was analyzed using Cox proportional hazards models. Results: During a mean follow-up of 12.2 years (SD: 3.2), 105 participants developed a stroke, of whom 81 had an ischemic event. Although there was no clear association between actigraphy-estimated sleep and the risk of stroke, a more fragmented 24-h activity rhythm was associated with a higher risk of stroke (hazard ratio [HR] per SD increase 1.28, 95% confidence interval [CI] 1.07–1.53). A less stable (HR per SD increase in stability 0.78, 95% CI: 0.63–0.97) and more fragmented (HR 1.28, 95% CI: 1.04–1.58) 24-h activity rhythm was also associated with a higher risk of ischemic stroke. Conclusions: Disturbed 24-h activity rhythms, but not sleep, are associated with a higher risk of stroke in middle-aged and elderly persons. This suggests that unstable and fragmented activity rhythms may play a more prominent role in the risk of stroke than sleep per se.

Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study.

Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males; Mage = 14.6 ± 2.3 yr) completed two study visits on weekdays bracketing an ambulatory assessment during summer vacation. Visit 1 included in-laboratory CRF assessment (peak V̇o2) using a ramp-type progressive cycle ergometry protocol and gas exchange measurement, which was followed by 7-14 days of actigraphy to assess sleep/wake patterns and 24-h activity rhythms. During Visit 2, chronotype, social jetlag (i.e., the difference in midsleep time between weekdays and weekends), and phase preference were assessed using a questionnaire, and hourly saliva samples were collected to determine the dim light melatonin onset (DLMO) phase. All analyses were adjusted for sex, pubertal status, and physical activity. Greater peak V̇o2 was associated with earlier sleep/wake times and circadian phase measures, including acrophase, UP time, DOWN time, last activity peak (LAP) time, and chronotype (all P < 0.05). Peak V̇o2 was negatively associated with social jetlag (P = 0.02). In addition, the mixed-model analysis revealed a significant interaction effect between peak V̇o2 and actigraphy-estimated hour-by-hour activity patterns (P < 0.001), with the strongest effects observed at around the time of waking (0600-1000). In healthy adolescents, better CRF was associated with an earlier circadian phase and increased activity levels notably during the morning. Future studies are needed to investigate the longitudinal effects of the interactions between CRF and advanced rhythms on health outcomes.NEW & NOTEWORTHY In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.

Fetal and infant growth patterns, sleep, and 24-h activity rhythms: a population-based prospective cohort study in school-age children.

The study objective was to explore associations of fetal and infant weight patterns and preterm birth with sleep and 24-h activity rhythm parameters at school-age. In our prospective population-based study, 1327 children were followed from birth to age 10-15 years. Fetal weight was estimated using ultrasound in the second and third trimester of pregnancy. Birth weight and gestational age were available from midwife registries. Infant weight was measured at 6, 12 and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change of >0.67 standard deviation between the corresponding age intervals. At school-age, sleep duration, sleep efficiency, wake after sleep onset, social jetlag, inter-daily stability, and intra-daily variability were assessed using tri-axial wrist actigraphy for 9 consecutive nights. We observed that low birth weight (<2500g) was associated with 0.24 standard deviation (95% confidence interval [CI] 0.04; 0.43) longer sleep duration compared to normal weight. Compared to normal growth, growth deceleration in fetal life and infancy was associated with 0.40 standard deviation (95% CI 0.07; 0.73) longer sleep duration, 0.44 standard deviation (95% CI 0.14; 0.73) higher sleep efficiency, and -0.41 standard deviation (95% CI -0.76; -0.07) shorter wake after sleep onset. A pattern of normal fetal growth followed by infant growth acceleration was associated with -0.40 standard deviation (95% CI -0.61; -0.19) lower inter-daily stability. Preterm birth was not associated with any sleep or 24-h rhythm parameters. Our findings showed that children with fetal and infant growth restriction had longer and more efficient sleep at school-age, which may be indicative of an increased need for sleep for maturational processes and development after a difficult start in life.

Measuring lamb activity during lactation by actigraphy

ABSTRACT Twenty-two lambs were used to determine their locomotor activity during lactation, and its circadian rhythm, based on data collected by actigraphy; the relationships among lambs were also measured calculating their proximity and distance. Lambs were fitted with Bluetooth-enabled (BT) accelerometers during weeks 1 and 4 of age, and data were downloaded as activity counts at 1-min intervals (Vector Magnitude, VM). Sensors were programmed as receivers and as beacons of the BT signal to calculate proximity (min/h) and distance (m) to another lamb. For each week, mean daily VM was calculated at hourly intervals. Circadian rhythms in VM were graphed by fitting the time-series measurements of each lamb to the cosine curve of a 24-h activity rhythm. Week of lactation and lamb sex had a significant (P < .05) effect on VM. Lambs had a higher (P < .05) VM (counts/min ±S.E.) in week 1 (154 ± 13) than in week 4 (117 ± 4), and female (113 ± 10) were more active (P < .01) than male lambs (113 ± 10). Twin lambs spent more time (P < .001) close to its sibling than to another lambs. Lamb activity followed a 24-h rhythm in week 4, only. In conclusion, actigraphy demonstrated that circadian rhythms in activity were not present in the first week of life, and twin-born lambs had stronger associations with their littermates than did singletons with other lambs, which reflected the strong bond that is established between twin lambs.

0132 Loss of Neurons in the Intermediate Nucleus is Related to Perturbed Sleep-Wake Rhythms in Older Adults

Abstract Introduction The ventrolateral preoptic nucleus (VLPO) is composed of neurons that are maximally active during sleep. In animal studies, VLPO lesion decreased the amount of sleep but only marginally attenuated circadian rhythm. The human intermediate nucleus (IN) is believed to be the homologue of the VLPO. Neuronal loss in IN has found to be associated with increased sleep fragmentation in older adults. We investigated whether IN neuronal loss is also associated with perturbed sleep-wake rhythms in humans. Methods We studied 50 deceased participants [age at death: 88.9±6.1 (mean±SD; female: 33 (66%)] from the Rush Memory and Aging Project, who had actigraphy assessment 1.6±1.3 years (range: 0.1-5.1 years) before death. Post-mortem immunohistochemical and stereological analysis was performed to quantify the count of galanin-immunoreactive neurons (Gal+) in the IN of them. Actigraphy data were used to calculate amplitude, acrophase, interdaily stability, and intradaily variability of the 24-h activity rhythms. Linear regression models were used to determine the associations of the four measures of sleep-wake rhythms with the GAL+ neuron counts, adjusting for age at death and sex. Further covariates considered included sleep fragmentation (derived from actigraphy) and the time interval between actigraphy assessment and death. Results The number of Gal+ neurons in IN was positively associated with interdaily stability and amplitude, and negatively associated with intradaily variability. Specifically, for one-SD decrease in Gal+ neurons, interdaily stability decreased by 0.06±0.02 (mean±standard error; equivalent to 40% SD of interdaily stability; p=0.009), amplitude decreased by 5.8±2.3 (equivalent to 35% SD of amplitude; p=0.014), and intradaily variability increased by 0.12±0.04 (equivalent to 36% SD of intradaily variability; p=0.009). Longer time interval between actigraphy and death showed a trend to attenuate these associations although not statistically significant (all p&amp;gt;0.1). These observations also remained statistically significant after adjusting for sleep fragmentation. Conclusion Neuronal loss in the IN was linked with perturbed sleep-wake rhythms in older adults. Further investigations are warranted to examine whether the observed associations are mediated by reduced sleep quantity or other aspects of sleep quality. Support (If Any) NIH RF1AG064312, RF1AG059867, R01AG017917, R01AG56352; and the BrightFocus Foundation A2020886S.

Identification of Geriatric Depression and Anxiety Using Activity Tracking Data and Minimal Geriatric Assessment Scales

The identification of geriatric depression and anxiety is important because such conditions are the most common comorbid mood problems that occur in older adults. The goal of this study was to build a machine learning framework that identifies geriatric mood disorders of depression and anxiety using low-cost activity trackers and minimal geriatric assessment scales. We collected activity tracking data from 352 mild cognitive impairment patients, from 60 to 90 in age, by having them wear activity trackers on their wrist for more than a month. We then extracted the features of 24-h activity rhythms and sleep patterns from the time-series activity tracking data. To increase the accuracy, we designed a novel method to incorporate additional features from questionnaire-based assessments of the geriatric depression scale and geriatric anxiety inventory into the activity tracking features. In the multi-label classification, we applied the binary relevance method to develop two single-label classifiers for depression and anxiety. The best hyper-parameters of classification algorithms for each label were selected by comparing the classification performance. We finally selected the combination of classifiers for depression and anxiety with the lowest Hamming loss as a multi-label classifier. This study successfully demonstrated the possibility of identifying geriatric depression and anxiety using low-cost activity trackers and minimal geriatric assessment scales for use in the real fields.

The bidirectional association of 24-h activity rhythms and sleep with depressive symptoms in middle-aged and elderly persons.

In older populations disturbed 24-h activity rhythms, poor sleep, and depressive symptoms are often lingering and co-morbid, making treatment difficult. To improve insights into these commonly co-occurring problems, we assessed the bidirectional association of sleep and 24-h activity rhythms with depressive symptoms in middle-aged and elderly persons. In 1734 participants (mean age: 62.3 ± 9.3 years, 55% women) from the prospective Rotterdam Study, 24-h activity rhythms and sleep were estimated with actigraphy (mean duration: 146 ± 19.6 h), sleep quality with the Pittsburgh Sleep Quality Index, and depressive symptoms with the Center for Epidemiological Studies Depression scale. Repeated measures were available for 947 participants (54%) over a median follow-up of 6 years (interquartile range = 5.6-6.3). Linear-mixed models were used to assess temporal associations of 24-h activity rhythms and sleep with depressive symptoms in both directions. High 24-h activity rhythm fragmentation (IV) (B = 1.002, 95% confidence interval (CI) = 0.641-1.363), long time in bed (TIB) (B = 0.111, 95% CI = 0.053-0.169), low sleep efficiency (SE) (B = -0.015, 95% CI = -0.020 to -0.009), long sleep onset latency (SOL) (B = 0.009, 95% CI = 0.006-0.012), and low self-rated sleep quality (B = 0.112, 95% CI = 0.0992-0.124) at baseline were associated with increasing depressive symptoms over time. Conversely, more depressive symptoms at baseline were associated with an increasing 24-h activity rhythm fragmentation (B = 0.002, 95% CI = 0.001-0.003) and TIB (B = 0.009, 95% CI = 0.004-0.015), and a decreasing SE (B = -0.140, 95% CI = -0.196 to -0.084), SOL (B = 0.013, 95% CI = 0.008-0.018), and self-rated sleep quality (B = 0.193, 95% CI = 0.171-0.215) over time. This study demonstrates a bidirectional association of 24-h activity rhythms, actigraphy-estimated sleep, and self-rated sleep quality with depressive symptoms over a time frame of multiple years in middle-aged and elderly persons.

758 Circadian rest-activity signatures in women with major depressive disorder

Abstract Introduction Patients with major depressive disorder (MDD) show disrupted circadian rhythms and sleep, including reduced daytime physical activity and poor sleep quality. However, previous findings are masked by psychotropic medication intake, co-morbid diseases and years of chronic mental illness. Here, we aim at identifying circadian motor activity patterns in unmedicated women at the onset of MDD. Methods Twelve young unmedicated women with MDD (Mean+-SD: 24.9+-5.2y; range: 18-33y) and eight age-matched healthy women (Mean+-SD: 24.5+-3.2y; range: 20-31y) participated in our study. Activity recordings were collected using wrist-worn wearable devices (actigraphs) for ~7 days in real-life settings. Cosinor analyses were performed to assess the amplitude and phase of the 24-h rest-activity activity rhythms. Non-parametric analyses were used to quantify interdaily stability and intradaily variability of the rest-activity rhythm. Furthermore, we calculated the mean activity level and scaling exponent alpha, which quantifies the temporal correlation in activity fluctuations, per 3-h bins across the 24-h sleep-wake cycle. Results Women with MDD showed a significantly higher amplitude of the 24-h rest-activity activity rhythm (Mean+-SD: 332.7+-120.8 arbitrary units) than the controls (179.7+-122.9; p=0.002), elicited by higher activity levels during the daytime (0-12h after habitual wake-up time; p&amp;lt;0.01). In contrast, women with MDD showed a trend for lower interdaily stability levels than controls (respectively, 0.41+-0.07 and 0.46+-0.08; p=0.05). Interestingly, a significant interaction effect of “group” and “time since habitual wake” was elicited for scaling exponent alpha (p&amp;lt;0.001). Accordingly, women with MDD had higher alpha values during habitual sleep (0–6 hours before habitual wake-up time) than controls (respectively, 1.18+-0.22 and 1.12+-0.22). Conclusion Unmedicated women at the onset of MDD had altered circadian motor activity patterns, as indexed by higher amplitude particularly during daytime while awake, less stable 24-h activity rhythms, and highly correlated activity patterns during sleep that closely resemble those typically occurring during wakefulness. These findings suggest that MDD per se may be associated with impaired rest-activity profiles. Ultimately, the use of wearable devices might hold important prospects for the early detection of individuals at risk for mood disorders. Support (if any) Swiss National Science Foundation Grants START #3100–055385.98, 3130-0544991.98 and 320000-108108; NIH RF1AG064312, RF1AG059867

Sleep, 24-h activity rhythms, and plasma markers of neurodegenerative disease

Sleep and 24-h activity rhythm disturbances are associated with development of neurodegenerative diseases and related pathophysiological processes in the brain. We determined the cross-sectional relation of sleep and 24-h activity rhythm disturbances with plasma-based biomarkers that might signal neurodegenerative disease, in 4712 middle-aged and elderly non-demented persons. Sleep and activity rhythms were measured using the Pittsburgh Sleep Quality Index and actigraphy. Simoa assays were used to measure plasma levels of neurofilament light chain, and additionally β-amyloid 40, β-amyloid 42, and total-tau. We used linear regression, adjusting for relevant confounders, and corrected for multiple testing. We found no associations of self-rated sleep, actigraphy-estimated sleep and 24-h activity rhythms with neurofilament light chain after confounder adjustment and correction for multiple testing, except for a non-linear association of self-rated time in bed with neurofilament light chain (P = 2.5*10−4). Similarly, we observed no significant associations with β-amyloid 40, β-amyloid 42, and total-tau after multiple testing correction. We conclude that sleep and 24-h activity rhythm disturbances were not consistently associated with neuronal damage as indicated by plasma neurofilament light chain in this population-based sample middle-aged and elderly non-demented persons. Further studies are needed to determine the associations of sleep and 24-h activity rhythm disturbances with NfL-related neuronal damage.

Circadian disturbances in Alzheimer's disease progression: a prospective observational cohort study of community-based older adults

SummaryBackgroundCircadian disturbances are commonly seen in people with Alzheimer’s disease and have been reported in individuals without symptoms of dementia but with Alzheimer’s pathology. We aimed to assess the temporal relationship between circadian disturbances and Alzheimer’s progression.MethodsWe did a prospective cohort study of 1401 healthy older adults (aged >59 years) enrolled in the Rush Memory and Aging Project (Rush University Medical Center, Chicago, IL, USA) who had been followed up for up to 15 years. Participants underwent annual assessments of cognition (with a battery of 21 cognitive performance tests) and motor activities (with actigraphy). Four measures were extracted from actigraphy to quantify daily and circadian rhythmicity, which were amplitude of 24-h activity rhythm, acrophase (representing peak activity time), interdaily stability of 24-h activity rhythm, and intradaily variability for hourly fragmentation of activity rhythm. We used Cox proportional hazards models and logistic regressions to assess whether circadian disturbances predict an increased risk of incident Alzheimer’s dementia and conversion of mild cognitive impairment to Alzheimer’s dementia. We used linear mixed-effects models to investigate how circadian rhythms changed longitudinally and how the change integrated to Alzheimer’s progression.FindingsParticipants had a median age of 81·8 (IQR 76·3–85·7) years. Risk of developing Alzheimer’s dementia was increased with lower amplitude (1 SD decrease, hazard ratio [HR] 1·39, 95% CI 1·19–1·62) and higher intradaily variability (1 SD increase, 1·22, 1·04–1·43). In participants with mild cognitive impairment, increased risk of Alzheimer’s dementia was predicted by lower amplitude (1 SD decrease, HR 1·46, 95% CI 1·24–1·72), higher intradaily variability (1 SD increase, 1·36, 1·15–1·60), and lower interdaily stability (1 SD decrease, 1·21, 1·02–1·44). A faster transition to Alzheimer’s dementia in participants with mild cognitive impairment was predicted by lower amplitude (1 SD decrease, odds ratio [OR] 2·08, 95% CI 1·53–2·93), increased intradaily variability (1 SD increase, 1·97, 1·43–2·79), and decreased interdaily stability (1 SD decrease, 1·35, 1·01–1·84). Circadian amplitude, acrophase, and interdaily stability progressively decreased over time, and intradaily variability progressively increased over time. Alzheimer’s progression accelerated these aging effects by doubling or more than doubling the annual changes in these measures after the diagnosis of mild cognitive impairment, and further doubled them after the diagnosis of Alzheimer’s dementia. The longitudinal change of global cognition positively correlated with the longitudinal changes in amplitude and interdaily stability and negatively correlated with the longitudinal change in intradaily variability.InterpretationOur results indicate a link between circadian dysregulation and Alzheimer’s progression, implying either a bidirectional relation or shared common underlying pathophysiological mechanisms.FundingNational Institutes of Health, and the BrightFocus Foundation.

Quantitative Study of Dual Circadian Oscillator Models under Different Skeleton Photoperiods.

The daily proportion of light and dark hours (photoperiod) changes annually and plays an important role in the synchronization of seasonal biological phenomena, such as reproduction, hibernation, and migration. In mammals, the first step of photoperiod transduction occurs in the suprachiasmatic nuclei (SCN), the circadian pacemaker that also coordinates 24-h activity rhythms. Thus, in parallel with its role in annual synchronization, photoperiod variation acutely shapes day/night activity patterns, which vary throughout the year. Systematic studies of this behavioral modulation help understand the mechanisms behind its transduction at the SCN level. To explain how entrainment mechanisms could account for daily activity patterns under different photoperiods, Colin Pittendrigh and Serge Daan proposed a conceptual model in which the pacemaker would be composed of 2 coupled, evening (E) and morning (M), oscillators. Although the E-M model has existed for more than 40 years now, its physiological bases are still not fully resolved, and it has not been tested quantitatively under different photoperiods. To better explore the implications of the E-M model, we performed computer simulations of 2 coupled limit-cycle oscillators. Four model configurations were exposed to systematic variation of skeleton photoperiods, and the resulting daily activity patterns were assessed. The criterion for evaluating different model configurations was the successful reproduction of 2 key behavioral phenomena observed experimentally: activity psi-jumps and photoperiod-induced changes in activity phase duration. We compared configurations with either separate light inputs to E and M or the same light inputs to both oscillators. The former replicated experimental results closely, indicating that the configuration with separate E and M light inputs is the mechanism that best reproduces the effects of different skeleton photoperiods on day/night activity patterns. We hope this model can contribute to the search for E and M and their light input organization in the SCN.

Nitrate application or P deficiency induce a decline in Medicago truncatula N2-fixation by similar changes in the nodule transcriptome

Nitrogen fixation of Medicago truncatula is regulated by the nitrogen status of leaves through inducing a repeatedly occurring 24-h nodule activity rhythm that reduces per day nitrogen fixation. The hypotheses of the present study were that (1) long-term moderate whole-plant P deficiency in Medicago truncatula induces an according daily rhythm in nitrogenase activity comparable to that induced by nitrate application and (2), the changes in the nodule transcriptome that go along with a strong nitrogenase activity decline during the afternoon would be similar under P deficiency or after nitrate supply. The nodules of plants in a low P treatment developed a rhythmic pattern of activity that resembled the pattern following nitrate application. A comprehensive, RNAseq-based comparative transcriptome profiling of nodules during a repeated part of the rhythm revealed similarities between P deficiency versus nitrate supply. Under both treatments, the formation of nitrogenase was targeted by a reduction in the expression of genes for nodule-specific cysteine-rich peptides (NCR), and possibly also by a disturbance of the inner cell iron allocation. A strong reduction in the expression of leghemoglobin is likely to have restricted the supply of oxygen for respiration.

24-h activity rhythm and sleep in depressed outpatients

Disturbances in sleep and circadian rest-activity rhythms are key features of depression. Actigraphy, a non-invasive method for monitoring motor activity, can be used to objectively assess circadian rest-activity rhythms and sleep patterns. While recent studies have measured sleep and daytime activity of depressed patients using wrist-worn actigraphy, the actigraphic 24-h rest-activity rhythm in depression has not been well documented. We aimed to examine actigraphically measured sleep and circadian rest-activity rhythms in depressed outpatients. Twenty patients with DSM-IV major depressive episode and 20 age- and sex-matched healthy controls participated in this study. Participants completed 7 consecutive days of all-day actigraphic activity monitoring while engaging in usual activities. For sleep parameters, total sleep time, wake after sleep onset, and sleep fragmentation index were determined. Circadian rhythms were estimated by fitting individual actigraphy data to a cosine curve of a 24-h activity rhythm using the cosinor method, which generated three circadian activity rhythm parameters, i.e., MESOR (rhythm-adjusted mean), amplitude, and acrophase. Subjective sleep was also assessed using a sleep diary and the Pittsburgh Sleep Quality Index. Patients showed significantly lower MESOR and more dampened amplitude along with significant sleep disturbances. Logistic regression analysis revealed that lower MESOR and more fragmented sleep emerged as the significant predictors of depression. Correlations between subjectively and actigraphically measured parameters demonstrated the validity of actigraphic measurements. These results indicate marked disturbances in sleep and circadian rest-activity rhythms of depression. By simultaneously measuring sleep and rest-activity rhythm parameters, actigraphy might serve as an objective diagnostic aid for depression.

Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study.

Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses. Higher white matter lesion volume (B=0.09 per SD, 95% confidence interval0.02; 0.15) and cerebral microbleeds (B=0.19 per SD, 95% confidence interval0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.

Associations of the 24-h activity rhythm and sleep with cognition: a population-based study of middle-aged and elderly persons

BackgroundCognitive functioning changes with age, sleep, and the circadian rhythm. We investigated whether these factors are independently associated with different cognitive domains assessed in middle-aged and elderly persons. MethodsIn 1723 middle-aged and elderly persons (age 62 ± 9.4 years, mean ± standard deviation, SD) of the Rotterdam Study, we collected actigraphy recordings of on average 138 h. Actigraphy was used to quantify 24-h rhythms by calculating the stability of the rhythm over days and the fragmentation of the rhythm. Sleep parameters including total sleep time, sleep-onset latency, and wake after sleep onset were also estimated from actigraphy. Cognitive functioning was assessed with the word learning test (WLT), word fluency test (WFT), letter digit substitution task (LDST), and Stroop color word test (Stroop). ResultsPersons with less stable 24-h rhythms performed worse on the LDST (B = 0.42 per SD increase, p = 0.004) and the Stroop interference trial (B = −1.04 per SD increase, p = 0.003) after full adjustment. Similarly, persons with more fragmented rhythms performed worse on the LDST (B = −0.47 per SD increase, p = 0.002) and the Stroop (B = 1.47 per SD increase, p < 0.001). By contrast, longer observed sleep-onset latencies were related to worse performance on the WLT delayed recall (B = −0.19 per SD increase, p = 0.027) and the WFT (B = −0.45 per SD increase, p = 0.007). ConclusionsDisturbances of sleep and the 24-h activity rhythm were independently related to cognition; while persons with longer sleep-onset latencies had worse performance on memory and verbal tasks, persons with 24-h rhythm disturbances performed less on executive functioning and perceptual speed tasks.

Sleep and 24-h activity rhythms in relation to cortisol change after a very low-dose of dexamethasone

The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in sleep. Nevertheless, the association of sleep and its 24-h organization with negative feedback control of the HPA axis has received limited attention in population-based studies. We explored this association in 493 middle-aged persons of the Rotterdam Study, a large population-based study (mean age 56 years, standard deviation: 5.3 years; 57% female). The negative feedback of the HPA axis was measured as the change in morning saliva cortisol after the intake of 0.25mg dexamethasone the night before. Actigraphy allowed us to measure the stability and fragmentation of the activity rhythm and to estimate total sleep time, sleep onset latency and wake after sleep onset. A sleep diary kept during the week of actigraphy was used to assess self-reported total sleep time, sleep onset latency, number of awakenings and perceived sleep quality. In our study, enhanced negative feedback of the HPA axis was found in association with unstable activity rhythms (B=0.106, 95% confidence interval (CI): 0.002; 0.210), total sleep time (B=0.108, 95%CI: 0.001; 0.215) and poor subjective sleep quality (B=0.107, 95%CI: 0.009; 0.206) after multivariate adjustment. These results indicated that the 24-h organization, duration and experience of sleep are all associated with the negative feedback control of the HPA axis.

Simulated shift work in rats perturbs multiscale regulation of locomotor activity.

Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation.

Leptin expression is rhythmic in brain and liver of goldfish (Carassius auratus). Role of feeding time

Daily rhythms of feeding regulators are currently arousing research interest due to the relevance of the temporal harmony of endocrine regulators for growth and welfare in vertebrates. However, it is unknown the leptin circadian pattern in fish. The aim of this study is to investigate if leptin (gLep-aI and gLep-aII) expression is rhythmic in goldfish (Carassius auratus) liver and brain, and if such rhythms are driven by feeding time through a food entrainable oscillator. Fish maintained under 12-h light:12-h dark photoperiod and a scheduled feeding time showed 24-h locomotor activity and glycaemia rhythms. Moreover, hepatic gLep-aI and brain gLep-aI and gLep-aII expression were rhythmic with different daily profiles, showing a postprandial increase of leptin expression in the liver but not in the brain. Under constant light and different feeding regimes (scheduled fed at 10:00, 22:00 or randomly fed), feeding time synchronized daily rhythms in locomotor activity, glycaemia and clock gene expression (gPer1a, gPer3 and gCry3), but the rhythmic expression of hepatic gLep-aI and brain gLep-aII only remained in fed fish at 10:00. In summary, daily rhythms of leptin expression in goldfish are differently regulated at central and peripheral level, and they are not directly driven by clock genes. The role of food entrained oscillators on leptin expression rhythms in fish remains to be demonstrated.

Stability and Fragmentation of the Activity Rhythm Across the Sleep-Wake Cycle: The Importance of Age, Lifestyle, and Mental Health

The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96 h (138 ± 14 h, mean ± SD) were collected from 1734 people (age: 62 ± 9.4 yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β = 0.07, p = 0.02), but also with a more fragmented distribution of periods of activity and inactivity (β = 0.20, p < 0.001). Having more depressive symptoms was related to less stable (β = −0.07, p = 0.005) and more fragmented (β = 0.10, p < 0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β = −0.11, p < 0.001; smoking: β = −0.11, p < 0.001) and more fragmented rhythms (BMI: β = 0.09, p < 0.001; smoking: β = 0.11, p < 0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.

P.4.a.001 Sleep disorders and obsessive-compulsive disorder

Disturbances in sleep and circadian rest-activity rhythms are key features of depression. Actigraphy, a non-invasive method for monitoring motor activity, can be used to objectively assess circadian rest-activity rhythms and sleep patterns. While recent studies have measured sleep and daytime activity of depressed patients using wrist-worn actigraphy, the actigraphic 24-h rest-activity rhythm in depression has not been well documented. We aimed to examine actigraphically measured sleep and circadian rest-activity rhythms in depressed outpatients. Twenty patients with DSM-IV major depressive episode and 20 age- and sex-matched healthy controls participated in this study. Participants completed 7 consecutive days of all-day actigraphic activity monitoring while engaging in usual activities. For sleep parameters, total sleep time, wake after sleep onset, and sleep fragmentation index were determined. Circadian rhythms were estimated by fitting individual actigraphy data to a cosine curve of a 24-h activity rhythm using the cosinor method, which generated three circadian activity rhythm parameters, i.e., MESOR (rhythm-adjusted mean), amplitude, and acrophase. Subjective sleep was also assessed using a sleep diary and the Pittsburgh Sleep Quality Index. Patients showed significantly lower MESOR and more dampened amplitude along with significant sleep disturbances. Logistic regression analysis revealed that lower MESOR and more fragmented sleep emerged as the significant predictors of depression. Correlations between subjectively and actigraphically measured parameters demonstrated the validity of actigraphic measurements. These results indicate marked disturbances in sleep and circadian rest-activity rhythms of depression. By simultaneously measuring sleep and rest-activity rhythm parameters, actigraphy might serve as an objective diagnostic aid for depression.