Intradaily Variability Research Articles

Rest-Activity Rhythm Is Associated With Obesity Phenotypes: A Cross-Sectional Analysis.

BackgroundThe prevalence of obesity continues to increase in spite of substantial efforts towards its prevention, posing a major threat to health globally. Circadian disruption has been associated with a wide range of preclinical and clinical disorders, including obesity. However, whether rest-activity rhythm (RAR), an expression of the endogenous circadian rhythm, is associated with excess adiposity is poorly understood. Here we aimed to assess the association of RAR with general and abdominal obesity.MethodsNon-institutionalized adults aged ≥20 years participating in the US National Health and Nutrition Examination Survey (NHANES) 2011-2014 who wore accelerometers for at least four 24-hour periods were included (N=7,838). Amplitude, mesor, acrophase and pseudo-F statistic of RAR were estimated using extended cosinor model, and interdaily stability (IS) and intradaily variability (IV) were computed by nonparametric methods. We tested the association between rest-activity rhythm and general obesity defined by body mass index and abdominal obesity by waist circumference. Waist-to-height ratio, sagittal abdominal diameter, and total and trunk fat percentages measured by imaging methods were also analyzed.ResultsIn multivariable analysis, low amplitude (magnitude of the rhythm), mesor (rhythm-corrected average activity level), pseudo-F statistic (robustness of the rhythm), IS (day-to-day rhythm stability), or high IV (rhythm fragmentation) were independently associated with higher likelihood of general or abdominal obesity (all Ps<.05). Consistently, RAR metrics were similarly associated with all adiposity measures (all Ps<.01). Delayed phase of RAR (later acrophase) was only significantly related to general and abdominal obesity in women.ConclusionsAberrant RAR is independently associated with anthropometric and imaging measures of general and abdominal obesity. Longitudinal studies assessing whether RAR metrics can predict weight gain and incident obesity are warranted.

Rest-activity rhythms and tract specific white matter lesions in older adults at risk for cognitive decline

White matter lesions (WMLs) are common in older adults and represent an important predictor of negative long-term outcomes. Rest-activity rhythm disturbance is also common, however, few studies have investigated associations between these factors. We employed a novel AI-based automatic WML segmentation tool and diffusion-weighted tractography to investigate associations between tract specific WML volumes and non-parametric actigraphy measures in older adults at risk for cognitive decline. The primary non-parametric measures of interest were inter-daily stability (IS), intra-daily variability and relative amplitude, with the anterior thalamic radiation (ATR), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) selected as tracts of interest. One hundred and eight participants at risk for cognitive decline (classified as experiencing subjective or objective cognitive decline) were included (mean age = 68.85 years, SD = 8.91). Of the primary non-parametric measures of interest, results showed that lower IS was associated with a greater likelihood of higher WML burden in the ATR (OR = 1.82, 95% CI [1.12,3.15]). Analysis of secondary non-parametric measures revealed later onset of the least active period to be associated with greater likelihood of high WML burden in the SLF (OR = 1.55, 95% CI [1.00,2.53]) and increased activity during the least active 5-h period to be associated with a greater likelihood of high whole-brain WML burden (OR = 1.83, 95% CI [1.06,3.47]). This study shows integrity of the ATR and SLF, and overall WML burden is linked to altered rest-activity rhythms in older adults at risk for cognitive decline, with those demonstrating altered rest-activity rhythms showing 50%-80% higher odds of having high WML burden.

Rest-Activity Rhythm Fragmentation and Weaker Circadian Strength Are Associated With Cognitive Impairment in Survivors of Acute Respiratory Failure.

Background: Survivors of acute respiratory failure (ARF) experience long-term cognitive impairment and circadian rhythm disturbance after hospital discharge. Although prior studies in aging and neurodegenerative diseases indicate actigraphy-estimated rest-activity circadian rhythm disturbances are risk factors for cognitive impairment, it is unclear if this applies to ARF survivors. This study explored the relationships of actigraphy-estimated rest-activity circadian rhythms with cognitive functioning in ARF survivors at 3months after discharge. Methods: 13 ARF survivors (mean age 51years and 69% males) completed actigraphy and sleep diaries for 9days, followed by at-home neuropsychological assessment. Principal component factor analysis created global cognition and circadian rhythm variables, and these first components were used to examine the global relationships between circadian rhythm and cognitive measure scores. Results: Global circadian function was associated with global cognition function in ARF survivors (r = .70, p = .024) after adjusting for age, education, and premorbid cognition. Also, greater fragmented rest-activity circadian rhythm (estimated by intradaily variability, r = .85, p = .002), and weaker circadian strength (estimated by amplitude, r = .66, p = .039; relative strength, r = .70, p = .024; 24-h lag serial autocorrelation, r = .67, p = .035), were associated with global cognition and individual cognitive tests. Conclusions: These results suggest circadian rhythm disturbance is associated with poorer global cognition in ARF survivors. Future prospective research with larger samples is needed to confirm these results and increase understanding of the relationship between disrupted circadian rhythms and cognitive impairment among ARF survivors.

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.

0056 Rest-Activity Rhythms (RARs) and Cognitive Functions in Early Post-menopausal Women

Abstract Introduction RAR disruptions are more common among individuals with dementia than healthy individuals. In healthy older women, RAR disruption predicted future diagnosis of Mild Cognitive Impairment (MCI). With no cure for Alzheimer’s Disease, it is crucial to identify modifiable risk-factors for early prevention of cognitive decline. Here we aim to determine whether RAR disruption was associated with cognitive status and cognitive performance in early post-menopausal women, thereby representing a modifiable risk factor for dementia. Methods The sample drawn from MsBrain study, included 229 cognitively unimpaired women and 42 women with MCI/dementia, based on score on Montreal Cognitive Assessment (MOCA) adjusted for age and race. Participants completed a 72-hour wrist actigraphy monitoring and neuropsychological assessment including: California Verbal Learning Test (CVLT), Letter Number Sequencing (LNS), Card Rotation Test, Symbol Digit Modalities Test (SDMT). Latent profile analysis (LPA) was performed using five nonparametric RAR variables (intra-daily variability (IV), inter-daily stability (IS), relative amplitude (RA), alpha and F-statistic). The association between RAR clusters and cognitive performance and the relationship between RAR clusters, cognitive status and race/ethnicity were assessed using linear regression models, controlling for age, race/ethnicity, education and body mass index (BMI); and using chi-square test respectively. Results LPA revealed three clusters: Robust with high F-Stat, RA and IS and low IV; Normal;Weak with low RA and high alpha. The proportion of subjects with MCI/dementia did not differ between clusters however there was a significant association between race and RAR clusters, X2 (2, N = 271)=14.18, p&amp;lt;0[P1] .001, with non-white women more likely than white women to belong in the Weak group (p &amp;lt; .01). In an adjusted analysis of healthy women, the Weak group performed worse than the Robust group in LNS control (p&amp;lt;.050 ). In the unadjusted model, the Weak group performed worse than Robust group in CVLT Total Learning and Long Delay Recall and SDMT (p=.0074, p=.011and p= .0041, respectively). Conclusion Non-white women had weaker RAR than their white counterparts. Weaker RARs related to poorer working memory as measured by LNS; and poorer verbal memory and processing speed, measured by CVLT and SDMT however these effects were largely influenced by covariates, particularly race/ethnicity and education. Support (If Any)

0207 Mothers’ Adverse Childhood Experiences and Protective Factors are Associated with Rest-activity Rhythms in their Children

Abstract Introduction Mothers’ history of adverse childhood experiences (ACEs; e.g. maltreatment, household dysfunction) are associated with poor health outcomes in their children, but mechanisms underlying this intergenerational transmission are poorly understood. Given links between circadian rhythm and the stress-response system, we test the hypothesis that maternal ACEs influence child health through disrupted rest-activity rhythm (RAR) in the mother and child. We also explore whether mothers’ benevolent childhood experiences (BCEs) are protective against disrupted RAR. Methods We conducted a cross-sectional pilot study of maternal-child dyads with preschool-age children. Mothers reported history of childhood adversity (ACEs Scale, Childhood Trauma Questionnaire) and protective factors (BCE Scale). Dyads wore wrist actigraphs for 8-10 days and mothers completed daily electronic diaries. Nonparametric measures of RAR (e.g. interdaily stability [IS], intradaily variability [IV]) were calculated. We used linear regression to examine associations between mothers’ childhood history and maternal and child RAR measures, controlling for household size and maternal employment. Results Maternal-child dyads (N=20) identified as white (75%), Black (15%), and Hispanic/Latina (10%). Mean child age was 4.2 years (40% female). Average household size was 4.5 ±.1.1 and 65% of mothers were employed. Forty-two percent of mothers reported 1-2 ACEs and 25% reported 3 or more ACEs. Maternal childhood history was not associated with mothers’ RAR. However, maternal ACEs and CTQ total score were associated with decreased child IS (ACEs: β= -0.47, SE=0.01, p=.02; CTQ total: β= -0.53, SE=.01, p=.001) and increased child IV (ACEs: β=0.29, SE=.01, p=.051; CTQ total: β=0.38, SE+.00, p=.03). CTQ subscales revealed maternal childhood physical abuse (β= -0.54, SE=.01, p&amp;lt;.0001), emotional abuse (β= -0.42, SE=.00, p=.002), and sexual abuse (β= -.73, SE=.00, p&amp;lt;.0001) were associated with decreased child IS, while maternal childhood emotional neglect was associated with increased child IV (β= 0.39, SE=.01, p=.04). Maternal BCEs were associated with decreased child IV (β= -0.44, SE=.01, p=.03). Conclusion Maternal ACE history may influence child health through effects on children’s circadian rhythm (i.e. decreased synchronization, increased fragmentation), while maternal BCEs may protect against rhythm fragmentation. Additional research is needed to support these novel preliminary findings. Support (If Any) National Institute of Nursing Research (K99NR018876) and American Nurses Foundation.

0159 Sleep-wake stability and variability in the middle-aged adult population: a UK Biobank study

Abstract Introduction Given the increasing use of consumer, wrist-worn devices with triaxial accelerometry (actigraphy), understanding whether 24-hr activity patterns are associated with specific mental and physical health deficits is of paramount importance. The UK Biobank, a community-based sample of adults in the United Kingdom, provides an opportunity to examine this question given its size (more than 100,000 actigraphy records) and scope (association health records). As a first step in understanding these relationships, understanding the impact of missing data, ways to interpolate missing data, and the general characteristics of 24-hr patterns is necessary. Methods A subset (n=70) of complete (i.e., no missing data) actigraphy records from individuals participating in the UK Biobank were used to examine the impact of missing data on intradaily variability (IV; rhythm fragmentation) and interdaily stability (IS; rhythm regularity). Data were intentionally removed and imputed and the impact of the manipulations was examined with Bland-Altman statistics. After determining the best imputation method and the limits of the method, it was applied to missing data in the full cohort, resulting in 82,840 actigraphy records. These were examined for IV and IS, as well as relative amplitude and the timing of L5 and M10. Data were categorized by age, gender, ethnicity, BMI and material deprivation. ANOVA with eta² effect sizes were used for comparisons. Data shown as median (interquartile range). Results Relative to IV and IS, median and mean imputation methods corrected for missing data of up to 24 hours. Linear imputation of long (&amp;gt;3 hours) missing data worsened IV and IS scores. Non-parametric patterns in the general population were within expected range, with IV=0.89(0.74-1.05), IS=0.55(0.46-0.63), RA=0.90(0.85-0.99), L5-timing=00:52 (00:07-01:37), and M10-timing=08:25(07:40-09:20). Stratifying by gender, age, ethnicity, BMI and material deprivation resulted in significant differences within all groups (p&amp;lt;0.0001), but small effect sizes (0.0019-0.00052). Conclusion Median imputation is useful for correcting for missing data (&amp;lt;24 hours) when examining IV and IS. Non-parametric analysis of the general population indicated values within the expected range. Even though there were significant differences in non-parametric outcomes between genders, age groups, ethnicities, body-mass index and material deprivation, none of these had significant effect sizes. Support (If Any) This research has been conducted using the UK Biobank Resource

0003 On the Same Wavelength? Quantifying the Associations between Eating Timing and Rest-Activity Rhythms in Free-Living Adults

Abstract Introduction Misalignment between the central circadian clock and daily behaviors increases cardiometabolic morbidity and mortality risk, likely due to internal misalignment between central and peripheral circadian rhythms. Experimental studies suggest food intake may act as a time cue (‘zeitgeber’) for resetting circadian rhythms, representing a potential behavioral target to ameliorate circadian misalignment and associated health consequences. However, the extent to which eating timing relates to circadian rhythms in free-living adults is unclear. Therefore, we tested the associations between eating timing with 24-h rest-activity-rhythms (RAR), a free-living proxy for endogenous circadian rhythms, in non-shift-working adults. Methods Adults without chronic health conditions or sleep disorders completed 14 days of 24/7 wrist accelerometry to evaluate RAR variables of interdaily stability (IS; day-to-day stability in RAR), intradaily variability (IV; within-day fragmentation of RAR), relative amplitude (RA; difference between peak vs. trough activity), L5 onset time (5-h period with lowest activity), and M10 onset time (10-h period with highest activity). Concurrently, time-stamped image-assisted diet records were obtained to generate average eating timing variables, including daily eating onset (time of first caloric intake after awakening), offset (last caloric intake time), duration (time elapsed between eating onset and offset), and caloric midpoint (time at which 50% of daily kcals were consumed), and variables illustrating irregularity in eating timing (standard deviation of eating timing variables). Pearson’s correlations quantified the associations between RAR and eating timing variables. Results Participants (N=30) were 28.0±6.6 years, 57% female, with a BMI of 23.8±2.5 kg/m2. Higher IS was correlated with lower irregularity in both eating onset (r=-0.55, p&amp;lt;0.01) and duration (r=-0.51, p&amp;lt;0.01). Higher RA correlated with earlier eating onset (r=-0.47, p&amp;lt;0.01), longer eating duration (r=0.53, p&amp;lt;0.01), and lower eating onset irregularity (r=-0.37, p&amp;lt;0.05). Later L5 correlated with later eating onset (r=0.67, p&amp;lt;0.001), offset (r=0.58, p&amp;lt;0.001), caloric midpoint (r=0.56, p&amp;lt;0.01), and greater eating offset irregularity (r=0.53, p&amp;lt;0.01). Later M10 correlated with later eating offset (r=0.40, p&amp;lt;0.05). Conclusion Preliminary findings indicate that eating timing and RAR are moderately correlated in free-living adults. Earlier eating timing, increased eating regularity, and longer daily eating duration may represent behavioral targets for improving circadian rhythms and subsequent cardiometabolic outcomes. Support (If Any): Support provided by the American Heart Association (#831488) and a University of Delaware Research Fund-Strategic Initiative Award.

0277 Deep learning revealed associations between altered temporal correlations in motor activity and Parkinson’s risk

Abstract Introduction Motor activity in healthy young adults displays fractal patterns with similar temporal correlations at different timescales. Altered fractal patterns were observed in patients with Parkinson’s disease. This study aimed to determine whether altered fractal patterns also predict the risk of Parkinsonism. Methods We studied 982 participants (age: 80.12±7.27 [SD]; 750 females) from the Rush Memory and Aging Project, who had at least one actigraphy assessment, had no symptoms of Parkinsonism at actigraphy baseline, and had follow-up clinical assessments. Detrended fluctuation analysis was performed on baseline actigraphy to determine the fractal patterns. Specifically, the activity fluctuation (around the trend) was computed at multiple timescales (n) ranging from 3-600 min. An exponential function with a variable scaling factor α was used to fit the local fluctuation function with respect to n. The α(n) that represented the temporal correlations was fed into a convolutional neural network (CNN) model whose output was further used as the input of a Cox proportional hazards model to predict the time to incident Parkinsonism. Covariates at baseline considered include age, sex, education, cognition, motor function, chronic health assessment, and actigraphy-derived measures including physical activity level, rest-activity/activity-rest transition probabilities, interdaily stability, and intradaily variability. Results There were 412 subjects who developed parkinsonism (in 4.75±3.13 [SD] years from baseline). Based on the gradient of hazard function (with respect to α) from the CNN model (estimated feature importance), the α in three timescale regions (i.e., 3-5 min, 12-20 min, and 270-600 min) contributed significantly to the prediction. Consistently, in separate Cox models with adjustment of age, sex, and education, the mean α at timescales 3-5 min was inversely associated with incident parkinsonism (for 1-SD increase, hazard ratio [HR]=0.82, 95% CI: 0.78-0.92, p&amp;lt;0.0001); The mean α at timescales 270-600 min was also inversely associated with incident Parkinsonism (HR=0.87, 95% CI: 0.78-0.96, p=0.008); And the mean α at timescales 10-25 min was marginally, positively associated with incident Parkinsonism (HR=1.10, 95% CI: 0.99-1.22, p=0.08). Conclusion Altered temporal correlations at specific timescales in motor activity predicted the risk of Parkinsonism. Support (If Any) NIH RF1AG064312, RF1AG059867, R01AG017917, R01AG56352, the BrightFocus Foundation A2020886S.

0195 Integrated actigraphy-based biomarker for the risk of Alzheimer’s dementia

Abstract Introduction Many physiological measures derived from actigraphy including physical activity, sleep, circadian/daily rhythm, and temporal correlations have been shown to predict Alzheimer’s dementia (AD). This study aimed to combine these actigraphy-based measures to develop an integrated actigraphy biomarker (IAB) for AD and to test its link to the genetic risk for AD. Methods We analyzed data of 1107 participants (age 80.9±7.3(mean±SD)) from the Rush Memory and Aging Project who were non-demented and had actigraphy (~10 days) at baseline, and had annual cognitive assessment during the follow-up (1-15 years). 270 developed AD (mean = 7.4 years). To construct the IAB for the AD’s risk, we trained a random forest survival model, in which time to incident AD was the outcome, and inputs included 10 features derived from actigraphy data: physical activity level, 3 features for sleep (sleep duration, sleep fragmentation, activity fragmentation), 4 features for circadian rhythmicity (amplitude, acrophase, interdaily stability, and intradaily variability of 24-hr rhythms), and 2 features for temporal correlations (at timescales between 1-90 min and 120-480 min). Polygenic risk score (PRS) was calculated using 457 independent SNPs strongly associated with Alzheimer’s disease (p&amp;lt;0.001). Cox proportional hazard ratio models were performed with different combinations of IAB, PRS, age, sex, and education, and the concordance score (C-score) was used to evaluate model performance. Results The derived IAB was 0.6 SD larger in the AD group as compared with the controls. The IAB alone achieved a C-score = 0.61 in predicting AD, with a hazard ratio=1.5 for 1-SD increase in IAB. The IAB and PRS were not correlated (r2=0.0004, p=0.25), and both significantly contributed to the prediction (both p&amp;lt;=0.0001) when included in one model, giving a C-score of 0.65. C-score was 0.7 in the model using only age, sex and educations yielded, and increased to 0.74 after including IAB and PRS (both effects remained significant p&amp;lt;0.0001). Conclusion The integrated actigraphy biomarker may provide complementary information for early prediction and detection of AD, independent of the known demographic and genetic risk factors. Support (If Any) NIH (RF1AG064312, RF1AG059867, R01AG56352, R01AG17917, T32GM007592, and R03AG067985); The BrightFocus Foundation (A2020886S).

0560 Rest-Activity Rhythms are Associated with Prevalent Cardiovascular Disease, Hypertension, Obesity, and Central Adiposity in a Nationally Representative Sample of US Adults

Abstract Introduction Prior studies have linked rest-activity rhythms (RAR), a measure of circadian rhythmicity in the free-living setting, to morbidity and mortality. However, evidence is limited on the associations of RAR with adiposity, hypertension, and cardiovascular disease (CVD) in a nationally representative sample of US adults. Methods Participants were 4,822 adults (age:≥20y) from the 2013-2014 National Health and Nutrition Examination Survey, who participated in the physical activity monitoring examination. Data from a wrist-worn ActiGraph GT3X+ accelerometer were used to estimate non-parametric 24-h RAR variables. Logistic models adjusted for age, sex, race/ethnicity, education, marital status, smoking, and alcohol use were used to evaluate associations of RARs with prevalent CVD (self-reported), hypertension (blood pressure≥130/80mmHg or medication use), obesity (BMI≥30kg/m2), and central adiposity (waist circumference&amp;gt;102cm for men and &amp;gt;88cm for women). Results Participants (mean age: 48y, 53% female, 33% racial/ethnic minority) in the highest vs. lowest tertile of relative amplitude, indicative of more robust RAR, had lower odds of prevalent CVD (OR(95%CI):0.47(0.25-0.87)), hypertension (OR(95%CI):0.63(0.40-0.99)), obesity (OR(95%CI):0.50(0.36-0.69)), and central adiposity (OR(95%CI):0.50(0.36-0.69)). Those in the highest vs. lowest tertile of M10 counts, indicating a more active wake period, had 66%, 54%, and 39% lower odds of CVD, obesity, and central adiposity, respectively. In contrast, participants in the highest vs. lowest tertile of intradaily variability, indicative of more fragmented RARs, had &amp;gt;2-fold (OR(95%CI):2.40(1.23-4.70)) and 40% (OR(95%CI):1.40(95%CI:1.04-1.88)) higher CVD and obesity odds, respectively. Further, those in the highest vs. lowest tertile of L5 midpoint, indicative of a later sleep period, had 68% and 41% higher odds for CVD and hypertension, while those with higher L5 counts, indicative of less efficient sleep, had 72%, 57%, and 79% higher hypertension, obesity, and central adiposity odds, respectively. A statistically significant linear trend was observed across RAR tertiles for all associations (p-trend&amp;lt;0.05). Conclusion Robust RAR, an active wake period, and an earlier and more efficient sleep period are associated with lower odds for CVD, hypertension, obesity, and central adiposity, with evidence of a dose-response relationship. The timing, regularity, and periodicity of sleep-wake and rest-activity patterns may represent an important target for reducing cardiovascular risk in adults. Support (If Any) NHLBI R00-HL148511; AHA grant #855050

0278 Isolated REM sleep behavior disorder is associated with 24-hour rhythm disruption

Abstract Introduction Isolated REM sleep behavior disorder (iRBD), the loss of motor inhibition during REM sleep, is a symptom of prodromal Lewy body disease, with over 80% of iRBD patients eventually phenoconverting to Parkinson’s disease or Dementia with Lewy bodies. Rest-activity rhythm disruption, also an established predictor of Parkinson’s disease, has not been well characterized in patients with iRBD. Here, we tested the hypothesis that accelerometer-based measures of 24-hour rhythms would indicate greater fragmentation and variability in patients with iRBD relative to matched healthy controls. Methods N=36 patients with iRBD recruited from the Stanford Sleep Clinic had 24-hour activity continuously monitored for (mean ± SD) 25.3 ± 8.4 days using an Axivity wristworn device. A control dataset of age, sex, and body mass index matched healthy older adults (N=126) was selected from the UK Biobank accelerometer dataset. Raw accelerometer data were processed using the GGIR, nparACT, and ActCR software packages in R, with a focus on nonparametric and 5-parameter cosinor measures of 24-hour rhythms. Functional PCA analyses (fPCA) were applied to detect overall differences in 24-hour rhythms and during sleep. Results Patients with iRBD had lower interdaily stability and higher intradaily variability than controls (IS, Cohen’s d=-1.15, Mann-Whitney test p&amp;lt;0.001; IV, d=0.46, p=0.04). Cosine amplitude was lower in iRBD patients (d=-0.22, p=0.001), but mean activity (mesor) did not differ (d=0.03, p=0.31), suggesting differences in rest-activity patterns rather than overall activity levels. A shape naïve approach utilizing fPCA indicated that increased activity during the night may explain overall rhythm differences observed in iRBD. Conclusion Multiple metrics of rest-activity rhythms support the hypothesis that 24-hour rhythms are disrupted in iRBD. It remains to be determined whether rhythm fragmentation in iRBD reflects higher activity levels during REM sleep, or if dysfunctional rhythms represent the direct effects of degenerating sleep-wake regulating circuits, indicating the early stages of Lewy body disease. Support (If Any) NIA F32AG074625 to JW; NIA P30AG066515 to JW, KP, and EM

Associations of actigraphy derived rest activity patterns and circadian phase with clinical symptoms and polysomnographic parameters in chronic insomnia disorders

We explored the associations of actigraphy-derived rest-activity patterns and circadian phase parameters with clinical symptoms and level 1 polysomnography (PSG) results in patients with chronic insomnia to evaluate the clinical implications of actigraphy-derived parameters for PSG interpretation. Seventy-five participants underwent actigraphy assessments and level 1 PSG. Exploratory correlation analyses between parameters derived from actigraphy, PSG, and clinical assessments were performed. First, participants were classified into two groups based on rest-activity pattern variables; group differences were investigated following covariate adjustment. Participants with poorer rest-activity patterns on actigraphy (low inter-day stability and high intra-daily variability) exhibited higher insomnia severity index scores than participants with better rest-activity patterns. No between-group differences in PSG parameters were observed. Second, participants were classified into two groups based on circadian phase variables. Late-phase participants (least active 5-h and most active 10-h onset times) exhibited higher insomnia severity scores, longer sleep and rapid eye movement latency, and lower apnea–hypopnea index than early-phase participants. These associations remained significant even after adjusting for potential covariates. Some actigraphy-derived rest-activity patterns and circadian phase parameters were significantly associated with clinical symptoms and PSG results, suggesting their possible adjunctive role in deriving plans for PSG lights-off time and assessing the possible insomnia pathophysiology.

Rest-activity circadian rhythm and impaired glucose tolerance in adults: an analysis of NHANES 2011-2014.

IntroductionCircadian rhythm disturbance occurs in type 2 diabetes, yet it is unknown whether it also exists in the prediagnostic phase of the disease. Thus, we examined the association of rest-activity circadian rhythm with 2-hour glucose levels and the risk of impaired glucose tolerance (IGT) in a nationally representative sample of adults without diabetes using a cross-sectional design.Research design and methodsWe analyzed data from 2760 adults without diabetes (age ≥20) with at least 4 days of validated accelerometer recordings and a valid oral glucose tolerance test from the National Health and Nutrition Examination Survey 2011–2014. Non-parametric rest-activity circadian rhythm parameters were derived from the accelerometer recordings.ResultsIn the models adjusting for multiple covariates, a one-quantile increase in relative amplitude (ie, increased circadian rhythmicity) was associated with 2.66 mg/dL decrease in 2-hour glucose level (95% CI −3.94 to −1.38, p<0.001) and a decreased odds of IGT (OR 0.75, 95% CI 0.63 to 0.89, p=0.002). A one-quantile increase in intradaily variability (ie, increased rhythm fragmentation) was associated with 3.01 mg/dL increase in 2-hour glucose level (95% CI 1.52 to 4.49, p=0.001) and an increased odds of IGT (OR 1.37, 95% CI 1.19 to 1.58, p<0.001).ConclusionsCircadian disruption is significantly associated with impaired glucose homeostasis in a general population of adults without diabetes. The association of circadian rhythm abnormalities with indicators of the pre-diabetic state suggests that circadian dysfunction may contribute to early disease pathogenesis.

Sleep and mental health in childhood: a multi-method study in the general pediatric population

BackgroundSleep problems, altered sleep patterns and mental health difficulties often co-occur in the pediatric population. Different assessment methods for sleep exist, however, many studies only use one measure of sleep or focus on one specific mental health problem. In this population-based study, we assessed different aspects of sleep and mother-reported mental health to provide a broad overview of the associations between reported and actigraphic sleep characteristics and mental health.MethodsThis cross-sectional study included 788 children 10-11-year-old children (52.5% girls) and 344 13–14-year-old children (55.2% girls). Mothers and children reported on the sleep of the child and wrist actigraphy was used to assess the child’s sleep patterns and 24 h activity rhythm. Mental health was assessed via mother-report and covered internalizing, externalizing and a combined phenotype of internalizing and externalizing symptoms, the dysregulation profile.ResultsHigher reported sleep problems were related to more symptoms of mental health problems in 10–11- and 13–14-year-old adolescents, with standardized ß-estimates ranging between 0.11 and 0.35. There was no association between actigraphy-estimated sleep and most mental health problems, but earlier sleep onset was associated with more internalizing problems (ß = − 0.09, SE = 0.03, p-value = 0.002), and higher intra-daily variability of the 24 h activity rhythm was associated with more dysregulation profile symptoms at age 10–11 (ß = 0.11, SE = 0.04, p-value = 0.002).DiscussionReported sleep problems across informants were related to all domains of mental health problems, providing evidence that sleep can be an important topic to discuss for clinicians seeing children with mental health problems. Actigraphy-estimated sleep characteristics were not associated with most mental health problems. The discrepancy between reported and actigraphic sleep measures strengthens the idea that these two measures tap into distinct constructs of sleep.

Disrupted Circadian Rest-Activity Cycles in Inflammatory Bowel Disease Are Associated With Aggressive Disease Phenotype, Subclinical Inflammation, and Dysbiosis.

Patients with inflammatory bowel disease (IBD)—Crohn's disease (CD), and ulcerative colitis (UC), have poor sleep quality. Sleep and multiple immunologic and gastrointestinal processes in the body are orchestrated by the circadian clock, and we recently reported that a later category or chronotype of the circadian clock was associated with worse IBD specific outcomes. The goal of this study was to determine if circadian misalignment by rest-activity cycles is associated with markers of aggressive disease, subclinical inflammation, and dysbiosis in IBD. A total of 42 patients with inactive but biopsy-proven CD or UC and 10 healthy controls participated in this prospective cohort study. Subjects were defined as having an aggressive IBD disease history (steroid dependence, use of biologic or immunomodulator, and/or surgery) or non-aggressive history. All participants did two weeks of wrist actigraphy, followed by measurement of intestinal permeability and stool microbiota. Wrist actigraphy was used to calculate circadian markers of rest-activity– interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). Aggressive IBD history was associated with decrease rest-activity stability (IS) and increased fragmentation compared to non-aggressive IBD and health controls at 0.39 ±.15 vs. 0.51 ± 0.10 vs. 0.55 ± 0.09 (P < 0.05) and 0.83 ± 0.20 vs. 0.72 ± 0.14 (P < 0.05) but not HC at 0.72 ± 0.14 (P = 0.08); respectively. There was not a significant difference in RA by IBD disease history. Increased intestinal permeability and increased TNF-α levels correlated with an increased rest activity fragmentation (IV) at R = 0.35, P < 0.05 and R = 0.37, P < 0.05, respectively; and decreased rest-activity amplitude (RA) was associated with increased stool calprotectin at R = 0.40, P < 0.05. Analysis of intestinal microbiota showed a significant decrease in commensal butyrate producing taxa and increased pro-inflammatory bacteria with disrupted rest-activity cycles. In this study, different components of circadian misalignment by rest-activity cycles were associated with a more aggressive IBD disease history, increased intestinal permeability, stool calprotectin, increased pro-inflammatory cytokines, and dysbiosis. Wrist activity allows for an easy non-invasive assessment of circadian activity which may be an important biomarker of inflammation in IB.

Cross-sectional study of intraocular cataract lens replacement, circadian rest-activity rhythms, and sleep quality in older adults.

Age-related cataract decreases light transmission at the most sensitive spectrum for circadian photoentrainment, with negative ramifications for human health. Here, we assessed whether intraocular lens replacement (IOL) in older patients with previous cataract was associated with increased stability and amplitude of circadian rest-activity rhythms, and improved sleep quality. Our cross-sectional study included sixteen healthy older individuals without ocular diseases (controls; 55-80 years; 63.6 ± 5.6y; 8 women) and 13 patients with previous cataract and bilateral IOL (eight with blue-blocking [BB] lens and five with ultraviolet-only [UV] blocking lens; 55-80 years; 69.9 ± 5.2y; 9 women). The study comprised three weeks of at home rest-activity assessments using wrist-worn actigraphs, and each week preceded a laboratory protocol. Primary outcomes were actigraphy-derived interdaily stability, intradaily variability, and relative amplitude of circadian rest-activity rhythms. Secondary outcomes were actigraphy-assessed sleep quality (i.e. time in bed, sleep duration, sleep efficiency, mean wake bout time and fragmentation index). Patients with IOL had significantly higher interdaily stability ("Group" effect: pFDR =.001), but not intradaily variability ("Group" effect: pFDR = n.s.), and significantly higher relative amplitude of rest-activity rhythms ("Group" effect: pFDR < .001). Moreover, patients with IOL had significantly higher activity levels during the day and lower levels during the evening, as compared to healthy older controls ("Group" effect: pFDR = .03). Analyses of actigraphy-derived sleep parameters yielded no significant differences across groups ("Group" effect: all pFDR > .1). Our cross-sectional study suggests that enhancing spectral lens transmission in patients with cataract may benefit their circadian health.

Relationship Between Circadian Strain, Light Exposure, and Body Mass Index in Rural and Urban Quilombola Communities.

Industrialization has greatly changed human lifestyle; work and leisure activities have been moved indoors, and artificial light has been used to illuminate the night. As cyclic environmental cues such as light and feeding become weak and/or irregular, endogenous circadian systems are increasingly being disrupted. These disruptions are associated with metabolic dysfunction, possibly contributing to increased rates of overweight and obesity worldwide. Here, we aimed to investigate how activity-rest rhythms, patterns of light exposure, and levels of urbanization may be associated with body mass index (BMI) in a sample of rural and urban Quilombola communities in southern Brazil. These are characterized as remaining social groups who resisted the slavery regime that prevailed in Brazil. Quilombola communities were classified into five groups according to their stage of urbanization: from rural areas with no access to electricity to highly urbanized communities. We collected anthropometric data to calculate BMI, which was categorized as follows: from ≥ 18.5 kg/m2 to < 25 kg/m2 = normal weight; from ≥ 25 kg/m2 to < 30 kg/m2 = overweight; and ≥ 30 kg/m2 = obese. Subjects were asked about their sleep routines and light exposure on workdays and work-free days using the Munich Chronotype Questionnaire (N = 244 included). In addition, we analyzed actimetry data from 121 participants with seven consecutive days of recordings. Living in more urbanized areas and higher intradaily variability (IV) of activity-rest rhythms were associated with an increased risk of belonging to the overweight or obese group, when controlling for age and sex. These findings are consistent with preclinical data and point to potential strategies in obesity prevention and promotion of healthy metabolic profiles.

Does the early bird really get the worm? How chronotype relates to human intelligence

• Morning chronotype is highly related to higher inter-daily stability ( i.e., the strength of circadian synchronization). • Overall, evening types have superior verbal abilities which contradicts the conventional wisdom that “the early bird gets the worm”. • However, higher ( i.e. , more morning) MEQ scores were related to superior verbal abilities after controlling for “bedtime” behaviours. Chronotype impacts our state at a given time of day, however, chronotype is also heritable, trait-like, and varies systematically as a function of age and sex. However, only a handful of studies support a relationship between chronotype and trait-like cognitive abilities ( i.e ., intelligence), and the evidence is sparse and inconsistent between studies. Typically, studies have: (1) focused on limited subjective measures of chronotype, (2) focused on young adults only, and (3) have not considered sex differences. Here, using a combination of cognitive aptitude and ability testing, subjective chronotype, and objective actigraphy, we aimed to explore the relationship between trait-like cognitive abilities and chronotype. Participants (N = 61; 44 females; age = 35.30 ± 18.04 years) completed the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) to determine subjective chronotype and wore an activity monitor for 10 days to objectively assess bedtime, rise-time, total sleep time, inter-daily stability, intra-daily variability, and relative amplitude. Cognitive ability ( e.g ., Verbal, Reasoning and Short-Term Memory) testing took place at the completion of the study. Higher MEQ scores ( i.e., more morning) were associated with higher inter-daily stability scores. Superior verbal abilities were associated with later bedtimes, younger age, but paradoxically, higher ( i.e. , more morning) MEQ scores. Superior STM abilities were associated with younger age only. The relationships between chronotype and trait-like cognitive abilities were similar for both men and women and did not differ between younger and older adults. The present study demonstrates that chronotype, measured by the MEQ, is highly related to inter-daily stability ( i.e., the strength of circadian synchronization). Furthermore, although evening types have superior verbal abilities overall, higher ( i.e. , more morning) MEQ scores were related to superior verbal abilities after controlling for “evening type” behaviours.

Circadian rhythms are not captured equal: Exploring Circadian metrics extracted by differentcomputational methods from smartphone accelerometer and GPS sensors in daily life tracking.

ObjectiveTo identify the differences between circadian rhythm (CR) metrics characterized by different mobile sensors and computational methods.MethodsWe used smartphone tracking and daily survey data from 225 college student participants, applied four methods (survey construct automation, cosinor regression, non-parametric method, Fourier analysis) on two types of smartphone sensor data (GPS, accelerometer) to characterize CR. We explored the inter-relations among the extracted circadian metrics as well as between the circadian metrics and participants’ self-reported mood and sleep outcomes.ResultsCompared to GPS signals, smartphone accelerometer activity follows an intradaily distribution that starts earlier in the day, winds down later, reaches half cumulative activity about the same time, conforms less to a sinusoidal wave, and exhibits more intradaily fragmentation but higher CR strength and lower interdaily disruption. We found a notable negative correlation between intradaily variability and CR strength especially pronounced in GPS activity. Self-reported sleep and mood outcomes showed significant correlations with particular CR metrics.ConclusionsWe revealed significant inter-relations and discrepancies in the circadian metrics discovered from two smartphone sensors and four CR algorithms and their bearings on wellbeing indicators such as sleep quality and loneliness.