Interdaily Stability Research Articles

Associations between Rest-Activity Rhythms and Liver Function Tests: The US National Health and Nutrition Examination Survey, 2011-2014.

Liver functions are regulated by the circadian rhythm; however, whether a weakened circadian rhythm is associated with impaired liver function is unclear. This study aims to investigate the association of characteristics of rest-activity rhythms with abnormal levels of biomarkers of liver function. Data were obtained from the National Health and Nutrition Examination Survey 2011-2014. Seven rest-activity rhythm parameters were derived from 24 h actigraphy data using the extended cosine model and non-parametric methods. Multiple logistic regression and multiple linear regression models were used to assess the associations between rest-activity rhythm parameters and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transaminase (GGT), albumin and bilirubin. Weakened overall rhythmicity characterized by a lower F statistic was associated with higher odds of abnormally elevated ALP (ORQ1vs.Q5: 2.16; 95% CI 1.19, 3.90) and GGT (ORQ1vs.Q5: 2.04; 95% CI 1.30, 3.20) and abnormally lowered albumin (ORQ1vs.Q5: 5.15; 95% CI 2.14, 12.38). Similar results were found for a lower amplitude, amplitude:mesor ratio, interdaily stability and intradaily variability. Results were robust to the adjustment of confounders and cannot be fully explained by individual rest-activity behaviors, including sleep and physical activity. Weakened rest-activity rhythms were associated with worse liver function as measured by multiple biomarkers, supporting a potential role of circadian rhythms in liver health.

54 Sleep and Circadian Rhythms in Premanifest Huntington’s disease: Relationship with Cognition

Objective:Huntington’s disease (HD) is a neurodegenerative disease characterised by motor, psychiatric and cognitive decline. Currently, no treatments have been identified in HD for slowing down cognitive decline or improving cognitive function. We are interested in identifying potentially modifiable factors in HD that can be targeted to improve or maintain cognitive function. Sleep and circadian disruption stand out as possible modifiable targets because sleep and circadian symptoms are common in HD, and such disruptions are known to impact cognition in the general population. Despite some emerging evidence that sleep quality correlates with cognition in manifest HD, whether these same relationships exist in the premanifest period is unknown. Further, whether circadian rhythms relate to cognition in premanifest HD remains open. Therefore, we aimed to determine whether sleep and circadian parameters relate to cognitive performance in premanifest HD.Participants and Methods:To date, we have recruited 27 premanifest HD participants to a two-week remote sleep study. During the study, participants wore an Actiwatch-2 and completed a sleep diary for 14 consecutive days to assess their sleep and rest-activity patterns. Participants also completed online sleep and mood questionnaires and a cognitive assessment using videoconference. We calculated Pearson correlations to examine whether cognitive performance relates to subjective sleep quality, objective sleep parameters and circadian rest-activity rhythms. Thus far, we have analysed data from 15 female participants with premanifest HD (Mage = 43.20, SD = 11.58).Results:Preliminary results indicate that measures of subjective sleep quality, insomnia severity, daytime sleepiness, and fatigue severity in premanifest HD do not correlate with cognitive performance. Increases in objectively measured sleep efficiency, however, strongly correlated with better performance on the Hopkins-Verbal Learning Test-Revised (HVLT-R) immediate (r = 0.562, p < 0.05) and delayed recall trials (r = 0.597, p < 0.05) and the Trail Making Test Part B (TMT-B; r = 0.550, p < 0.05). More time spent awake (i.e., wake after sleep onset) was strongly linked to reduced performance on the TMT-B (r = -0.542, p < 0.05) and Symbol Digit Modalities Test (r = -0.556, p < 0.05). Further, increases in total sleep time were associated with better performance on the HVLT-R immediate (r = 0.682, p < 0.05) and delayed recall trial (r = 0.616, p < 0.05). For our circadian parameters, less fragmented day-today rest-activity rhythms (i.e., higher intra-daily variability) strongly correlated with higher scores on the HVLT-R immediate (r = 0.768, p < 0.001) delayed recall trials (r = 0.7276, p < 0.05) and TMT-B (r = 0.516, p < 0.05), whereas consistent and stable day-to-day rest-activity rhythms (i.e., higher inter-daily stability) was associated with poorer performance on ERT (r = -0.587, p < 0.05).Conclusions:Preliminary results suggest that fragmented sleep, sleep inefficiency, reduced total sleep time, rest-activity rhythm stability and fragmentation relate to poorer cognitive performance in people with premanifest HD. Should analysis of our whole sample confirm these preliminary findings, targeting sleep in HD (e.g., through sleep hygiene and/or psychoeducation) may be a useful strategy to improve or maintain cognition.

P049 Actigraphic rest-activity rhythms in older adults ‘at risk’ for dementia: associations with reduced cortical thickness in frontal, temporal and occipital cortices

Abstract Background Rest-activity rhythm disturbance is common in older adults ‘at risk’ for dementia. This may be an early marker of underlying disease pathology and risk of future decline. However, our understanding of how rest-activity rhythm relates to brain integrity remains unclear. Methods This study used vertex-wise analyses to examine the association between nonparametric actigraphy measures and cortical thickness in older adults ‘at risk’ for dementia. Primary measures of interest were intra-daily variability (IV), relative amplitude (RA), inter-daily stability (IS), and average activity during the least active 5-hour period (L5). Results 143 older adults ‘at risk’ for cognitive decline were included (mean age=67.41, SD=7.96). Higher IV was associated with lower cortical thickness in the right cuneus (CWP< 0.001), left middle frontal gyrus (CWP< 0.001) and lateral orbital frontal cortex (CWP=0.004). Higher L5 was linked with cortical thinning in the left superior temporal sulcus (CWP=0.004), superior middle temporal cortex (CWP=0.010) and middle temporal gyrus (CWP=0.013), as well as right inferior parietal lobe (CWP< 0.001). Lower IS was associated with cortical thinning in the left (CWP=0.002) and right (CWP< 0.001) superior frontal gyri, left superior temporal gyrus (CWP=0.043) and left post-central gyrus (CWP=0.033). Conclusions Markers of circadian rhythmicity are associated with reduced cortical thickness in frontal, temporal and occipital cortices in older adults ‘at risk’ for dementia. Future work is still required to delineate whether brain degeneration leads to altered daily rhythms and/or if circadian misalignment contributes to cognitive decline longitudinally.

THU303 The Associations Between Rest-Activity Parameters, Sleep-Disordered Breathing Severity And Glucose Metabolism In Patients With Prediabetes

Abstract Disclosure: J. Paewponsong: None. B.S. Gerber: None. N. Chirakalwasan: None. S. Saetung: None. T. Anothaisintawee: None. S. Reutrakul: None. Background: Circadian rhythm abnormalities and sleep-disordered breathing (SDB) can have an adverse effect on glucose metabolism. In addition, studies have suggested that SDB itself could be associated with circadian disruption. This study aimed to determine if circadian characteristics, as measured by rest-activity rhythm parameters, were connected with SDB severity in individuals with prediabetes, and whether rest-activity rhythm parameters were related with glycemia. Methods: A total of 79 patients with prediabetes were enrolled. Actigraphy recordings (Actiwatch 2, Phillips Respironics) spanning 7 days yielded non-parametric rest-activity rhythm parameters and sleep duration. The parameters included M10 (mean activity of the most active 10-h period), L5 (mean activity of the least active 5-h period), intradaily variability (reflecting rhythm fragmentation), interdaily stability (reflecting sleep regularity across days), and relative amplitude (reflecting the activity between M10 and L5 activity). SDB was assessed using an overnight sleep monitor (WatchPAT200). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) were obtained via phlebotomy. Independent predictors of rest-activity rhythm parameters, FBG, and HbA1c were determined using multiple stepwise regression analyses. Model covariates included age, sex, body mass index (BMI), and SDB severity. Results: Increasing SDB severity was associated with lower M10 and greater intradaily variability, but not with FBG, HbA1c or other rest-activity rhythm parameters. After adjusting for age, sex and BMI, increasing SDB severity was independently related with lower M10 (B= -0.102, p=0.001). Further, bivariate analyses showed that a higher HbA1c was associated with a shorter sleep duration, lower relative amplitude, and higher L5. FBG was not related to any rest-activity rhythm parameters. After adjusting for age, sex, BMI and sleep duration, lower relative amplitude, but not L5, was independently related with higher HbA1c (B= −0.027, p=0.031). Conclusion: In prediabetes, a lower relative amplitude, indicating a less robust 24 hour rest-activity rhythm, was associated with a higher HbA1c. These findings suggest that circadian rhythmicity contributes to glycemic control. Greater SDB severity was correlated with decreased activity, but relationships with other rest-activity rhythm parameters were not observed. Presentation: Thursday, June 15, 2023

Deep representation learning identifies associations between physical activity and sleep patterns during pregnancy and prematurity

Preterm birth (PTB) is the leading cause of infant mortality globally. Research has focused on developing predictive models for PTB without prioritizing cost-effective interventions. Physical activity and sleep present unique opportunities for interventions in low- and middle-income populations (LMICs). However, objective measurement of physical activity and sleep remains challenging and self-reported metrics suffer from low-resolution and accuracy. In this study, we use physical activity data collected using a wearable device comprising over 181,944 h of data across N = 1083 patients. Using a new state-of-the art deep learning time-series classification architecture, we develop a ‘clock’ of healthy dynamics during pregnancy by using gestational age (GA) as a surrogate for progression of pregnancy. We also develop novel interpretability algorithms that integrate unsupervised clustering, model error analysis, feature attribution, and automated actigraphy analysis, allowing for model interpretation with respect to sleep, activity, and clinical variables. Our model performs significantly better than 7 other machine learning and AI methods for modeling the progression of pregnancy. We found that deviations from a normal ‘clock’ of physical activity and sleep changes during pregnancy are strongly associated with pregnancy outcomes. When our model underestimates GA, there are 0.52 fewer preterm births than expected (P = 1.01e − 67, permutation test) and when our model overestimates GA, there are 1.44 times (P = 2.82e − 39, permutation test) more preterm births than expected. Model error is negatively correlated with interdaily stability (P = 0.043, Spearman’s), indicating that our model assigns a more advanced GA when an individual’s daily rhythms are less precise. Supporting this, our model attributes higher importance to sleep periods in predicting higher-than-actual GA, relative to lower-than-actual GA (P = 1.01e − 21, Mann-Whitney U). Combining prediction and interpretability allows us to signal when activity behaviors alter the likelihood of preterm birth and advocates for the development of clinical decision support through passive monitoring and exercise habit and sleep recommendations, which can be easily implemented in LMICs.

Actigraphic characterization of sleep and circadian phenotypes of PER3 gene VNTR genotypes

ABSTRACT The molecular circadian timing system involves genes known as “clock genes,” such as the PER3 gene. Studies have demonstrated associations among a repeat polymorphism (VNTR) of the PER3 gene with chronotypes, with the occurrence of circadian rhythm disorders and with sleep homeostasis phenotypes. The aim of this study was to investigate, by actigraphy, sleep and circadian rhythm profiles of people with different genotypes for the VNTR polymorphism of the PER3 gene. We genotyped 467 individuals (46,39% male) for the PER3 VNTR polymorphism. The mean age of the participants was 21.84 2.64, ranging from 18 to 30 y old. Actigraphy data were collected from a subsample of 81 subjects with PER3 4-repeats homozygous (PER3 4/4 ) or 5-repeats homozygous (PER3 5/5 ) genotypes from April to June of 2021. From this sample, 48 PER3 4/4 and 33 PER3 5/5 subjects wore a wrist actigraph between 12 and 19 d. The sleep onset (weekdays, p = 0.015; weekend, p = 0.022) and offset (weekdays, p = 0.004; weekend, p = 0.041) of the PER3 5/5 group occurred later than the PER3 4/4 group. Similar results were observed for the mid-sleep phase of weekdays (MSW) (p = 0.008) and free days (MSF) (p = 0.019), and for the mid-sleep phase corrected for sleep debt accumulated over the week (MSFsc) (p = 0.024). Despite the phase differences found between the PER3 4/4 and PER3 5/5 groups, no differences were found in sleep duration and social jet lag. However, the PER3 4/4 group presented, on average, a longer sleep rebound on the days off when compared to the PER3 5/5 (p = 0.002). The PER3 5/5 group showed lower interdaily stability (IS) (p = 0.032) and higher daily activity rhythm variability (IV) (p = 0.035). The findings of the present study revealed associations between the PER3 gene, sleep, and circadian rhythms. In general, we found that the gene is associated with the expression of sleep timing and duration and to the phase of the activity rhythm. The experiments carried out here occurred in the COVID-19 pandemic scenario, which should be considered as an environmental element with potential effects on the results obtained.

The rest-activity rhythm, genetic susceptibility and risk of type 2 diabetes: A prospective study in UK Biobank.

This study aims to examine the association between the rest-activity rhythm (RAR) and the incidence of type 2 diabetes (T2D). In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter-daily stability, intra-daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D-PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D-PRS on the occurrence of T2D. During 692 257 person-years follow-ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HRRA = 2.06, 95% CI: 1.76-2.41; HRM10 = 1.33, 95% CI: 1.19-1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55-2.24). The joint analysis showed that the high T2D-PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HRRA = 4.46, 95% CI: 3.36-6.42; HRM10 = 3.15, 95% CI: 2.29-4.32; HRL5 = 3.09, 95% CI: 2.40-3.99). No modification effects of T2D-PRS on the association between the RAR parameters and risk of T2D were observed (p > .05). The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D.

Rest-activity rhythms across the lifespan: cross-sectional findings from the US representative National Health and Nutrition Examination Survey.

Rest-activity rhythms (RAR) may mark development, aging, and physical and mental health. Understanding how they differ between people may inform intervention and health promotion efforts. However, RAR characteristics across the lifespan have not been well-studied. Therefore, we investigated the association between RAR measures with demographic and lifestyle factors in a US nationally representative study. RAR metrics of interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), and mean amplitude and timing of high (M10) and low (L5) activity were derived from 2011 to 2012 and 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) actigraphy data. Population-weighted linear and logistic regression models were fit to examine the associations of age, gender, smoking, alcohol, season, body mass index (BMI), income-to-poverty ratio, and race/ethnicity with RAR. Significance was based on a false-discovery rate-corrected P-value of <0.05. Among n = 12 526 NHANES participants (3-≥80 years), IS (higher = greater day-to-day regularity) and RA (higher = greater rhythm strength) generally decreased with age and were lower among males, whereas IV (higher = greater rhythm fragmentation) increased with age (p < 0.05). Dynamic changes in RAR trajectories were observed during childhood and adolescence. Income, BMI, smoking, and alcohol use were associated with RAR metrics, as well as season among children and teenagers (p < 0.05). RAR also differed by race/ethnicity (p < 0.05), with trajectories initially diverging in childhood and continuing into adulthood. RAR differed by demographic and health-related factors, representing possible windows for public health intervention and sleep health promotion. RAR differences by race/ethnicity begin in childhood, are evident in early adolescence, and persist throughout adulthood.

Characterizing light-dark cycles in the Neonatal Intensive Care Unit: a retrospective observational study.

Objectives: To characterize bedside 24-h patterns in light exposure in the Neonatal Intensive Care Unit (NICU) and to explore the environmental and individual patient characteristics that influence these patterns in this clinical setting. Methods: We conducted a retrospective cohort study that included 79 very preterm infants who stayed in an incubator with a built-in light sensor. Bedside light exposure was measured continuously (one value per minute). Based on these data, various metrics (including relative amplitude, intradaily variability, and interdaily stability) were calculated to characterize the 24-h patterns of light exposure. Next, we determined the association between these metrics and various environmental and individual patient characteristics. Results: A 24-h light-dark cycle was apparent in the NICU with significant differences in light exposure between the three nurse shifts (p < 0.001), with the highest values in the morning and the lowest values at night. Light exposure was generally low, with illuminances rarely surpassing 75 lux, and highly variable between patients and across days within a single patient. Furthermore, the season of birth and phototherapy had a significant effect on 24-h light-dark cycles, whereas no effect of bed location and illness severity were observed. Conclusion: Even without an official lighting regime set, a 24-h light-dark cycle was observed in the NICU. Various rhythmicity metrics can be used to characterize 24-h light-dark cycles in a clinical setting and to study the relationship between light patterns and health outcomes.

Chronic social stress blunts core body temperature and molecular rhythms of Rbm3 and Cirbp in mouse lateral habenula

Chronic social stress in mice causes behavioural and physiological changes that result in perturbed rhythms of body temperature, activity and sleep-wake cycle. To further understand the link between mood disorders and temperature rhythmicity in mice that are resilient or susceptible to stress, we measured core body temperature (Tcore) before and after exposure to chronic social defeat stress (CSDS). We found that Tcore amplitudes of stress-resilient and susceptible mice are dampened during exposure to CSDS. However, following CSDS, resilient mice recovered temperature amplitude faster than susceptible mice. Furthermore, the interdaily stability (IS) of temperature rhythms was fragmented in stress-exposed mice during CSDS, which recovered to control levels following stress. There were minimal changes in locomotor activity after stress exposure which correlates with regular rhythmic expression of Prok2 - an output signal of the suprachiasmatic nucleus. We also determined that expression of thermosensitive genes Rbm3 and Cirbp in the lateral habenula (LHb) were blunted 1 day after CSDS. Rhythmic expression of these genes recovered 10 days later. Overall, we show that CSDS blunts Tcore and thermosensitive gene rhythms. Tcore rhythm recovery is faster in stress-resilient mice, but Rbm3 and Cirbp recovery is uniform across the phenotypes.

Activity-Rest Circadian Rhythm of the Pearly Razorfish in Its Natural Habitat, before and during Its Mating.

Recent technological advances in marine biotelemetry have demonstrated that marine fish species perform activity-rest rhythms that have relevant ecological and evolutionary consequences. The main objective of the present report is to study the circadian rhythm of activity-rest of the pearly razorfish, Xyrichtys novacula in its own habitat, before and during the reproduction season using a novel biotelemetry system. This fish species is a small-bodied marine species that inhabits most shallow soft habitats of temperate areas and has a high interest for commercial and recreational fisheries. The activity of free-living fish was monitored by means of high-resolution acoustic tracking of the motor activity of the fish in one-minute intervals. The obtained data allowed the definition of the circadian rhythm of activity-rest in terms of classical non-parametric values: interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), average activity during the most-active period of consecutive 10 h (M10), and average activity during the least-active period of consecutive 5 h (L5). We observed a well-marked rhythm, with little fragmentation and good synchrony with the environmental cycle of light-darkness, regardless of sex and the period studied. However, the rhythm was found to be slightly more desynchronized and fragmented during reproduction because of variations in the photoperiod. In addition, we found that the activity of the males was much higher than that of the females (p < 0.001), probably due to the peculiar behavior of the males in defending the harems they lead. Finally, the time at which activity began in males was slightly earlier than it was in females (p < 0.001), presumably due to the same fact, as differences in activity or for the individual heterogeneity of this species in the time of awakening are considered to be an independent axis of the fish's personality. Our work is novel, as it is one of the first studies of activity-rest rhythm using classical circadian-related descriptors in free-living marine fish using locomotory data facilitated by novel technological approaches.

Characteristics of 24-hour movement behaviours and their associations with mental health in children and adolescents

BackgroundTime-use estimates are typically used to describe 24-hour movement behaviours. However, these behaviours can additionally be characterised by other easily measured metrics. These include sleep quality (e.g., sleep efficiency), 24-hour rest-activity rhythmicity (e.g., between-day rhythm variability), and directly measured acceleration metrics (e.g., intensity gradient). Associations between these characteristics and youth mental health are unclear. This study aimed to [1] compare 24-hour movement behaviour characteristics by sex and age groups, [2] determine which movement behaviour characteristics were most strongly associated with mental health outcomes, and [3] investigate the optimal time-use behaviour compositions for different mental health outcomes.MethodsThree-hundred-and-one children and adolescents (age 9–13 y; 60% girls) wore accelerometers for 24-hours/day over 7-days. Overall mental health, externalising, and internalising problems were self-reported using the Strengths and Difficulties Questionnaire. 24-hour movement behaviour characteristics were categorised as time-use estimates, sleep quality, 24-hour activity rhythmicity, and directly measured acceleration. Linear mixed models and compositional data analysis were used to analyse the data in alignment with the study aims.ResultsTime-use estimates, directly measured accelerations, and 24-hour rest-activity rhythm metrics indicated that children were significantly more physically active (p = .01-<0.001) than adolescents. Children were also less sedentary (p < .01), slept longer (p = .02-0.01), and had lower sleep efficiency. Boys were significantly more active than girls (p < .001) who in turn accrued more time in sleep (p = .02). The timing of peak activity was significantly later among adolescents (p = .047). Overall mental health and externalising problems were significantly associated with sleep, sedentary time, sleep efficiency, amplitude, and inter-daily stability (p = .04-0.01). The optimal time-use compositions were specific to overall mental health and externalising problems and were characterised by more sleep, light and vigorous physical activity, and less sedentary time and moderate physical activity than the sample’s mean time-use composition.ConclusionsExtracting and examining multiple movement behaviour characteristics from 24-hour accelerometer data can provide a more rounded picture of the interplay between different elements of movement behaviours and their relationships with mental health than single characteristics alone, such as time-use estimates. Applying multiple movement behaviour characteristics to the translation of research findings may enhance the impact of the data for research users.

Circadian disturbances, risk for postoperative delirium and conversion to dementia

AbstractBackgroundDelirium is one of the most common complications in older adults after surgery. Circadian rest‐activity rhythms are known to be disrupted with age, and among individuals with mild cognitive impairment and Alzheimer’s disease (AD), major risk factors for postoperative delirium (POD). However, the relationship between prior circadian rest‐activity rhythm measures and POD, and whether these measures can predict conversion from delirium to dementia has not been systematically assessed.Method64,852 UK biobank participants between 2013‐2015 (mean 57.9y [SD = 8.0], 54.0% female) were assessed with actigraphy for 7 days, followed by at least one surgical event requiring hospitalization during follow‐up until 2021. Four measures were extracted from actigraphy to quantify circadian rest‐activity rhythms, which were amplitude (representing the strength), acrophase (representing peak activity time), interdaily stability (IS), and intradaily variability (IV; representing the fragmentation) of 24‐h rhythm. Earliest occurrence of delirium and dementia were determined using ICD‐10 coding from hospitalization records, and POD was defined as delirium within 3 days of an operation. Cox proportional hazards models were used to assess whether circadian disturbances in these rhythms predicted increased risk for delirium including POD, and logistic regression for the risk of conversion from delirium to dementia within 5 years of the first delirium occurrence.ResultRisk for new POD during hospitalization (n = 249) was increased with lower amplitude (1 SD decrease, hazard ratio [HR] 1.28, 95% CI: 1.10‐1.49, p = 0.002), and higher intradaily variability (1 SD increase, 1.30, 1.12–1.51, p&lt;0.001) after controlling for demographics, lifestyle factors, cardiovascular risk, and morbidity burden. These results were consistent when all new delirium cases during hospitalization (n = 500) were included. Within 5 years, 47 developed incident dementia. Every 1‐SD decrease in amplitude within a cohort of was associated with increased odds of incident dementia (odds ratio 1.44, 1.06‐1.96, p = 0.02) independent of age at first delirium and sex.ConclusionThese results indicate a link between circadian disturbances and risk for delirium, as well as conversion to incident dementia. This is novel evidence that circadian disturbances are part of the shared common underlying pathophysiological mechanisms between delirium and dementia that warrant further investigation.

0107 Rest-activity rhythmicity across the lifespan: findings from the National Health and Nutrition Examination Survey (NHANES)

Abstract Introduction Non-parametric metrics of interdaily stability (IS), relative amplitude (RA), and intradaily variability (IV) characterize between- and within-day rest-activity rhythms. Prior research has reported differences in these metrics by age and race/ethnicity, but these differences have not been widely assessed in children and adolescents. Therefore, we investigated associations of these metrics with sociodemographic factors across the lifespan, including children, in a US-representative cross-sectional study. Methods Rest-activity metrics were derived from actigraphy data (wrist-worn GT3X+ ActiGraph devices) measured over one week in the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Pregnant participants and participants with &amp;lt; 4 days of valid data were excluded; missing activity data were imputed and pooled using Rubin’s rule. Population-weighted linear and ordinal logistic regression (quartiles) models were fit to examine the associations of age, gender, smoking, body mass index (BMI), income-to-poverty ratio, and self-reported race/ethnicity with rhythmicity measures. Stratified analyses by age groups were conducted. Results There were n=12,526 participants aged 3-80 years. In adjusted analyses, IS and RA (higher: stronger rhythms) decreased with age and were lower among men, whereas IV (higher: weaker rhythm, greater fragmentation) increased with age (p&amp;lt; 0.05). Higher income-to-poverty ratio associated with higher RA (1-unit OR=1.11, 95%CI:1.06,1.16) and IV (1-unit OR=1.10, 95%CI:1.07,1.13). Greater BMI associated with lower RA and IS and higher IV (p&amp;lt; 0.05). Smoking associated with decreased values for all metrics. Compared to the non-Hispanic White group, the Asian, non-Hispanic Black, and Other/Multiracial groups were more likely to have lower RA, lower IS, and higher IV (p&amp;lt; 0.05). Compared to the non-Hispanic White group, the Mexican American (OR=0.83, 95%CI:0.72,0.95) and Other Hispanic (OR=0.83, 95%CI:0.73,0.94) groups were less likely to have higher IV. Analyses stratified by age (≤18, &amp;gt;18 years) resulted in similar patterns among the Asian, non-Hispanic Black, and Other/Multiracial groups (p&amp;lt; 0.05). Conclusion Rest-activity rhythms differ by age, gender, BMI, income, smoking, and race/ethnicity, representing possible windows for public health intervention and sleep health promotion. Differences in rest-activity measures by race/ethnicity begin in childhood, are evident in early adolescence, and persist throughout adulthood. Future analyses will evaluate the contribution of environmental factors to these differences. Support (if any) NIH-NHLBI T32HL007901, R35HL135818

0023 Circadian fragmentation and stability distinguish employment status

Abstract Introduction This analysis used data from the Assessing Daily Activity Patterns Through Occupational Transitions (ADAPT) study to compare differences in employment status on activity variability, as an indicator of circadian fragmentation and stability. Circadian fragmentation refers to frequency of alterations between rest and activity relative to the daily rhythm and stability refers to day-to-day similarity. High fragmentation and low stability have been linked to a number of negative health outcomes including depression, obesity, and heightened mortality risk. Methods The sample consisted of 155 participants that included 702 total cases (n = 434 employed, n = 268 unemployed) assessed over 18 months. Participants were required to have involuntarily lost their jobs in the last 90 days. Employment status was determined for all participants at each visit based on demographic surveys. Daily activity patterns were assessed via actigraphy (Actiwatch-Spectrum) at 30 second epochs for 14 days. The nonparametric measures of intradaily variability (IV) and interdaily stability (IS) were used as measures of circadian fragmentation and stability. Several subsampling intervals were considered for IV, ranging from 5 minutes to 4 hours. Results Unemployment was associated with higher IV (for 1 hour subsampling intervals, t=5.23, p &amp;lt; .001) and lower IS than employment (t=2.38, p &amp;lt;.05). The same is true with changes in the subsampling interval for IV, with highest significance at 45 minutes to 1.5 hours. Significant findings remained even for 5 minute (t=2.15, p &amp;lt; .05) and 4 hour (t = 4.07, p&amp;lt;.001) intervals. Conclusion In a sample of adults with variable employment status, employment was associated with less circadian fragmentation and more stability than unemployment. These findings suggest that circadian fragmentation and instability may be two mechanisms by which job loss increases negative health risk. Future planned studies examining prospective changes in circadian fragmentation/stability during employment transitions will help answer this question. Support (if any) NIH #1R01HL117995-01A1, NSF DMS 1937229, NSF CCF 1740858

0162 The neural bases of emotion dysregulation in rotating shift workers

Abstract Introduction Shift work is known to be associated with sleep disturbance and circadian misalignment and may contribute to alterations in the brain implicated in emotion dysregulation. In this study, we examined 1) neural correlates of emotion dysregulation, including emotional reactivity and regulation in shift workers and 2) relationships between neural correlates of emotion dysregulation, sleep disturbance, and circadian misalignment. Methods Fifty-six rotating shift workers (SW, 42 females, 30.80 ± 6.94 years old) who had non-standard shift schedules and 52 healthy controls (HC, 36 females, 31.69 ± 7.86 years old) who did not work as shift schedules participated in this study. Both SW and HC completed self-reported measures of sleep and mood problems, and wrote sleep diary and wore actigraphy to assess sleep quality and circadian rhythms. They also underwent one night polysomnography and were scanned while they were performing the emotion regulation task. We analyzed group differences in mood, sleep, circadian rhythms, and neural bases of emotional reactivity and regulation, and examined relationships between these variables. Results SW showed significant differences in actigraphy-estimated sleep (i.e., lower sleep efficiency) and circadian rhythms (e.g., greater motor activity [M10] and lower interdaily stability) compared to HC. SW also exhibited increased anterior insula (AI) activation in response to negative pictures, but reduced activation in the dorsomedial prefrontal cortex (dMPFC) and AI-dMPFC functional connectivity during emotion regulation compared to HC. AI activation and AI-dMPFC functional connectivity were significantly associated with sleep disturbance (i.e., sleep diary-estimated sleep onset latency) and circadian misalignment (e.g., M10 and interdaily stability). Furthermore, a mediation analysis revealed that shift work was associated with increased motor activity during the most active 10-hour period, which then contributed to increased AI activation in response to negative pictures. Conclusion Our findings suggest that shift work may contribute to sleep disturbance and circadian misalignment, and neural alterations associated with emotional reactivity and regulation. Furthermore, the mediation result suggests that increased motor activity along with misaligned circadian rhythm may serve as a pathway, through shift work contributes to heightened emotional reactivity to negative information. Support (if any) National Research Foundation (No. 2022R1A2C2008417, NRF-2022R1A2C1008209) and Korea Institute for Advancement of Technology (No. 20009210).

0099 Circadian Rest-Activity Rhythm Development is associated with Weight Gain in Early Infancy

Abstract Introduction In early childhood, irregular sleep schedules that may promote circadian rhythm misalignment predict greater weight gain. However, circadian rest-activity (CRA) rhythmicity in infancy in relation to growth is understudied. The aim of the present study was to investigate the association between newborn circadian rest-activity rhythmicity and change in weight-for-age from birth to three months. Methods Data were captured as a secondary data analysis from the Snuggle Bug / Acurrucadito Study (see Support). English or Spanish speaking mothers (n=41, age M±SD=33.1±4.6y, 31.7% Hispanic/Latina) and their full-term (≥37wk) infants of normal weight (2.5-4kg; 58.5% female; 25.6% WIC enrolled) were recruited from Phoenix, Arizona. CRA rhythmicity was measured at eight weeks with ankle-worn Micro Motionloggers (Ambulatory Monitoring Inc.) for five 24hr periods at one-minute epochs. CRA metrics assessed included 24hr autocorrelation, mesor, magnitude, acrophase, goodness-of-fit R2, interdaily stability, intradaily variability, and relative amplitude. Birthweight was mother-reported and 3mon infant weight was measured with a Seca scale. Weight-for-age Z-scores (WAZ) by infant sex were computed based upon World Health Organization growth charts and the change difference between timepoints was the primary outcome. Regression models adjusting for birth WAZ examined the relationships between CRA metrics at eight weeks with change in WAZ from birth to 3mo. Results At eight weeks, mean±SD CRA metrics were as follows: 24hr autocorrelation of 0.25±0.03, mesor of 115.6±14.7, amplitude of 68.1±18.3, goodness-of-fit R2 of 0.42±0.10, acrophase of 14:12±1:42, interdaily stability of 0.57±0.12, intradaily variability of 0.93±0.19, and relative amplitude of 0.61±0.11. Mean birth WAZ and change in WAZ from birth to 3mon were 0.39±0.73 and -0.57±0.77, respectively. After adjusting for birth WAZ, in separate models, greater mesor (R2 Change=0.10, β=-0.32, p=0.03), amplitude (R2 Change=0.11, β=-0.34, p=0.03), and goodness-of-fit R2 (R2 Change=0.10, β=-0.32, p=0.04) were significantly associated with less change in WAZ from birth to 3mon. Conclusion Among relatively healthy, full-term infants born of normal weight, greater 24hr circadian rest-activity rhythmicity achieved by 8 weeks was associated with slower rate of weight gain across the newborn stage. Promoting behaviors and environmental cues from parents that strengthen early circadian rhythmicity in their infants may promote healthy weight trajectories. Support (if any) NIH/NHLBI R01HL147931

0262 Comparing Wrist Actigraphy to a Novel Wearable (Actigpatch): Nonparametric Activity Estimation

Abstract Introduction Wrist actigraphy is a standard for monitoring sleep in the field; however, data quality is reduced if participants remove the device. The Actigpatch is a novel, adhesive water-resistant wearable that we have previously demonstrated as comparable to wrist actigraphy for traditional sleep-wake estimation. Here we compare assessment of nonparametric activity indexes. Methods While following fixed schedules, 39 participants simultaneously wore the Micro Motionlogger actigraph (Ambulatory Monitoring Inc., Ardley, NY) on their non-dominant wrist and the Actigpatch (Circadian Positioning Systems, Newport, RI) over the triceps of their dominant arm. Our analyses included 35 participants (21F; 32.9±13.2yrs) who contributed ≥four nights of data (range: 4-14 [mean: 10] nights). After matching devices’ tri-axial actimetry in one-minute epochs, we derived key non-parametric parameters of diurnal activity and calculated intraclass correlations to measure agreement. The non-parametric parameters include interdaily stability (IS), intradaily variability (IV), timing of the five hours of lowest activity (L5onset) and ten hours of highest activity (M10onset), and overall relative amplitude (RA). Results We observed agreement ranging from good for IS (ICC=0.77 [95%CI=0.59;0.88]; [all mean differences are patch-watch] mean difference=-0.21) to poor for IV (ICC=0.43 [0.12;0.67]; mean difference=0.29). ICC showed good agreement for M10onset (ICC=0.82 [0.67; 0.90]; mean difference=-37min) and excellent agreement for L5onset (ICC=0.91 [0.82;0.95]; mean difference=-2min). Finally, we identified good agreement when estimating the activity relative amplitude (RA ICC=0.86 [0.75; 0.93]; mean difference=0.03). An example of excellent agreement was manifested in the close estimation of L5onset (patch mean=1:04am, SD=70min; watch mean=1:06am, SD=68min). Conclusion Adding to our prior evidence that these two devices offer similar sleep-wake estimation using traditional algorithms, the present data indicate the Actigpatch offers good agreement to the Motionlogger for nonparametric analyses of IS, activity timing, and RA. Agreement was not as good for IV, with the Actigpatch showing more intradaily variability than the watch, perhaps due to the triceps placement. Because the Actigpatch is unobtrusive, water-resistant, and can be worn continuously for three weeks, it has potential benefits for studies of individuals who struggle with adherence to wearing wrist worn devices. Support (if any) R01AA025593, P20GM139743. Actigpatches provided by Circadian Positioning Systems.

0282 Behavioral–social rhythms and metabolic syndrome prevalence in retired night shift and day workers

Abstract Introduction Disrupted sleep and circadian rhythms, such as those occurring during night shift work, are established cardiovascular disease (CVD) risk factors like hypertension, obesity, and insulin resistance. However, we do not know whether the effects of shift work on CVD risk factors persist into retirement. Conversely, regularity in behavioral-social rhythms – the systematic patterning or timing of daily routines like work/housework, sleeping, eating and social interactions – may keep endogenous circadian rhythms synchronized to the 24-hour day and reduce CVD risk. This study examined: 1) whether behavioral–social rhythms are associated with a major CVD risk factor, prevalent metabolic syndrome, in retired night shift workers and day workers; and 2) whether past night shift work exposure moderates the associations between behavioral–social rhythm and metabolic syndrome prevalence. Methods Participants were 71 retired night shift workers (39 women (54.9%), 32 men (45.1%)) and 83 retired day workers (46 women (55.4%), 37 men (44.6%)), with mean age 68.4 (5.4) years. Logistic regression models were used to examine associations between behavioral–social rhythms and metabolic syndrome prevalence. Independent variables included Social Rhythm Metric-5 (SRM5; a 5-item scale to quantify rhythms of daily life) score and actigraphy rest-activity rhythm inter-daily stability (IS; rhythm stability across days) and intra-daily variability (IV; rhythm fragmentation within days). The dependent variable was metabolic syndrome prevalence. Results More regular behavioral-social rhythms were associated with lower odds of having metabolic syndrome (SRM5: OR=0.57, 95%CI [0.35, 0.88]; IV (Higher score means lower regularity): OR=2.05, 95%CI [1.23, 3.44]). In addition, more regular behavioral-social rhythms were associated with lower odds of having two individual components of metabolic syndrome , body mass index (SRM5: OR=0.56, 95%CI [0.37, 0.85]; IV: OR=2.05, 95%CI [1.30, 3.23]) and high-density lipoprotein cholesterol level (SRM5: OR=0.49, 95%CI [0.30, 0.80]; IV: OR=1.78, 95%CI [1.06, 2.98]). Shift work exposure did not moderate the association between behavioral–social rhythms and metabolic syndrome prevalence. Conclusion Behavioral–social rhythms are related to metabolic syndrome prevalence in retired adults regardless of prior shift work exposure. Older retired workers may benefit from interventions that promote behavioral–social rhythm regularity. Support (if any) This research was supported by the NIH grants AG047139, HL082610, MH019986, and AG07517

Objectively assessed sleep and physical activity in depression subtypes and its mediating role in their association with cardiovascular risk factors

The aims of this study were to investigate the associations of major depressive disorder (MDD) and its subtypes (atypical, melancholic, combined, unspecified) with actigraphy-derived measures of sleep, physical activity and circadian rhythms; and test the potentially mediating role of sleep, physical activity and circadian rhythms in the well-established associations of the atypical MDD subtype with Body Mass Index (BMI) and the metabolic syndrome (MeS). The sample consisted of 2317 participants recruited from an urban area, who underwent comprehensive somatic and psychiatric evaluations. MDD and its subtypes were assessed via semi-structured diagnostic interviews. Sleep, physical activity and circadian rhythms were measured using actigraphy. MDD and its subtypes were associated with several actigraphy-derived variables, including later sleep midpoint, low physical activity, low inter-daily stability and larger intra-individual variability of sleep duration and relative amplitude. Sleep midpoint and physical activity fulfilled criteria for partial mediation of the association between atypical MDD and BMI, and physical activity also for partial mediation of the association between atypical MDD and MeS. Our findings confirm associations of MDD and its atypical subtype with sleep and physical activity, which are likely to partially mediate the associations of atypical MDD with BMI and MeS, although most of these associations are not explained by sleep and activity variables. This highlights the need to consider atypical MDD, sleep and sedentary behavior as cardiovascular risk factors.