Rest-activity Rhythm Research Articles

In vivo tau deposition in the brain stem nuclei and circadian rest‐activity rhythm change in non‐demented older adults

AbstractBackgroundCircadian rest‐activity rhythm (RAR) alterations are common in the early stage of Alzheimer’s disease (AD) disease. Given that the brainstem nuclei, the locus coeruleus (LC) and dorsal raphe nucleus (DRN) in particular, play key roles in modulating arousal and the sleep‐wake cycle, tau pathology in the brain stem nuclei, which occurs even before cortical tau progression, may relate to circadian RAR alteration in older individuals. Therefore, we aimed to test the hypothesis that in vivo tau deposition in the LC and DRN correlates with circadian RAR in non‐demented older adults.MethodA total of 63 non‐demented older adults from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) were included. All participants underwent [11C] PiB PET and [18F] AV1451‐PET. Circadian RAR variables were measured using actigraphy for 8 consecutive days. Tau deposition of the LC and DRN (LC‐tau and DRN‐tau, respectively) was measured in the regions of interest (ROI) masks for each participant prepared in native space using the Harvard arousal network atlas for the LC and DRN. For the purpose of comparison, tau deposition in the substantia nigra (SN‐tau) was also measured in the neuromelanin sensitive MRI‐based ROI for the SN.ResultIncreased LC‐tau and DRN‐tau were significantly correlated with delayed acrophase (ß = 0.303, p = 0.024 for LC‐tau and ß = 0.398, p = 0.003 for DRN‐tau; Table 1 & Figure 1). In contrast, SN‐tau did not related with any RAR variables. Even after controlling for global tau deposition, the significance did not changed (ß = 0.321, p = 0.021 for LC‐tau and ß = 0.367, p = 0.008 for DRN‐tau, Table 1). In addition, Aß positivity showed a significant moderation effect on the relationship between LC‐tau with acrophase. Subgroup analyses showed that increased LC‐tau significantly related with delayed acrophase in Aß‐positivegroup (ß = 0.427, p = 0.004), but did not in Aß‐negative group (ß = 0.099, p = 0.615)(Figure 2)ConclusionOur findings support the possibility that the tau pathology in the LC and DRN underlie circadian RAR alteration, more specifically delayed phase, in non‐demented older adults. In addition, such relationship appears to be more prominent in individuals with brain Aß pathology.

In vivo tau deposition in the brain stem nuclei and circadian rest‐activity rhythm change in non‐demented older adults

AbstractBackgroundCircadian rest‐activity rhythm (RAR) alterations are common in the early stage of Alzheimer’s disease (AD) disease. Given that the brainstem nuclei, the locus coeruleus (LC) and dorsal raphe nucleus (DRN) in particular, play key roles in modulating arousal and the sleep‐wake cycle, tau pathology in the brain stem nuclei, which occurs even before cortical tau progression, may relate to circadian RAR alteration in older individuals. Therefore, we aimed to test the hypothesis that in vivo tau deposition in the LC and DRN correlates with circadian RAR in non‐demented older adults.MethodA total of 63 non‐demented older adults from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) were included. All participants underwent [11C] PiB PET and [18F] AV1451‐PET. Circadian RAR variables were measured using actigraphy for 8 consecutive days. Tau deposition of the LC and DRN (LC‐tau and DRN‐tau, respectively) was measured in the regions of interest (ROI) masks for each participant prepared in native space using the Harvard arousal network atlas for the LC and DRN. For the purpose of comparison, tau deposition in the substantia nigra (SN‐tau) was also measured in the neuromelanin sensitive MRI‐based ROI for the SN.ResultIncreased LC‐tau and DRN‐tau were significantly correlated with delayed acrophase (β = 0.303, p = 0.024 for LC‐tau and β = 0.398, p = 0.003 for DRN‐tau; Table 1 & Figure 1). In contrast, SN‐tau did not related with any RAR variables. Even after controlling for global tau deposition, the significance did not changed (β = 0.321, p = 0.021 for LC‐tau and β = 0.367, p = 0.008 for DRN‐tau, Table 1). In addition, Aβ positivity showed a significant moderation effect on the relationship between LC‐tau with acrophase. Subgroup analyses showed that increased LC‐tau significantly related with delayed acrophase in Aβ‐positivegroup (β = 0.427, p = 0.004), but did not in Aβ‐negative group (β = 0.099, p = 0.615)(Figure 2)ConclusionOur findings support the possibility that the tau pathology in the LC and DRN underlie circadian RAR alteration, more specifically delayed phase, in non‐demented older adults. In addition, such relationship appears to be more prominent in individuals with brain Aβ pathology.

Circadian rhythms in older adults are associated with sleep quality, cognitive function, and ß‐amyloid burden: an accelerometry analysis of the Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial ‐ LEARNit

AbstractBackgroundSeveral studies demonstrate circadian rhythm disturbances in patients with Alzheimer’s disease. However, less is known about circadian rhythms in older adults with early mild cognitive impairment. Wrist‐worn accelerometers provide continuous, objective, high resolution quantification of 24‐hour rest activity rhythms. This study examines the relationship between circadian rhythms and sleep, cognition, and ß‐amyloid (Aß) burden.MethodThis study examines baseline data from the “Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial” (LEARNit). Sixty‐six older adults ages 55‐80 experiencing early cognitive changes wore a GENEActiv accelerometer for approximately 30 consecutive days. Accelerometer data was analyzed using the R package GGIR (version 2.8‐1), and circadian rhythm measures were extracted using the GGIR secondary package ActCR (version 0.3.0). Circadian rhythm variables include intradaily variability (fragmentation), interdaily stability (rhythm synchronization to light‐dark cycle), acrotime (peak activity time), and Midline Estimated Statistics of Rhythm or MESOR (mean activity level). Up‐MESOR and Down‐MESOR represent the timing of activity increasing above or decreasing below MESOR, respectively—lower values of each indicate a phase advance (shift towards morning), whereas higher values indicate a phase delay (shift towards evening). Sleep was assessed as mean sleep efficiency and Wake After Sleep Onset, or WASO (accumulated wakefulness after sleep onset). Cognitive tests include the Montreal Cognitive Assessment (MoCA) for global cognition and attention/processing speed (Digit Symbol Task). Aß burden was measured by positron emission tomography standard uptake value ratio for fifty‐six participants. Age‐adjusted linear regression models were used to test associations between circadian rhythms and sleep, cognition, and Aß.ResultParticipant characteristics are summarized in Table 1 and results are summarized in Figure 1. Intradaily variability (b = ‐0.095, p = 0.03) and interdaily stability (b = 0.34, p = 0.01) were both associated with mean sleep efficiency. Intradaily variability (b = 1.41, p<0.001) and interdaily stability (b = ‐4.45, p<0.001) were associated with WASO. Up‐MESOR was associated with MoCA total score (b = ‐0.41, p = 0.03). Up‐MESOR (b = ‐2.12, p = 0.006), Down‐MESOR (b = ‐1.99, p = 0.02), and acrotime (b = ‐4.20, p<0.001) were associated with Digit Symbol score. Down‐MESOR was significantly associated with Aß (b = ‐0.029, p = 0.02).ConclusionCircadian rhythm robustness is positively associated with better sleep quality. Participants with dynamic circadian rhythm phases demonstrated poorer cognition and higher Aß burden.

MiR-277 regulates the phase of circadian activity-rest rhythm in Drosophila melanogaster.

Circadian clocks temporally organize behaviour and physiology of organisms with a rhythmicity of about 24h. In Drosophila, the circadian clock is composed of mainly four clock genes: period (per), timeless (tim), Clock (Clk) and cycle (cyc) which constitutes the transcription-translation feedback loop. The circadian clock is further regulated via post-transcriptional and post-translational mechanisms among which microRNAs (miRNAs) are well known post-transcriptional regulatory molecules. Here, we identified and characterized the role of miRNA-277 (miR-277) expressed in the clock neurons in regulating the circadian rhythm. Downregulation of miR-277 in the pacemaker neurons expressing circadian neuropeptide, pigment dispersing factor (PDF) advanced the phase of the morning activity peak under 12h light: 12h dark cycles (LD) at lower light intensities and these flies exhibited less robust rhythms compared to the controls under constant darkness. In addition, downregulation of miR-277 in the PDF expressing neurons abolished the Clk gene transcript oscillation under LD. Our study points to the potential role of miR-277 in fine tuning the Clk expression and in maintaining the phase of the circadian rhythm in Drosophila.

Effect of Personalized Blue-Enriched White Light Intervention on Rest-Activity and Light Exposure Rhythms in Mild and Moderate Alzheimer's Disease.

We aimed to examine the effectiveness of personalized light intervention using a blue-enriched light-emitting-diodes device on rest-activity rhythm (RAR) and light exposure rhythm (LER) in patients with mild and moderate Alzheimer's disease (AD). AD patients with poor sleep quality and/or insomnia symptoms were assigned into either an experimental group (EG) or control group (CG) in a single-blind design. Personalized light intervention was given at 9-10 h after individual dim light melatonin onset, lasting for 1 h every day for two weeks in the EG (77.36±5.79 years, n=14) and CG (78.10±7.98 years, n=10). Each patient of CG wore blue-attenuating sunglasses during the intervention. Actigraphy recording at home for 5 days was done at baseline (T0), immediate postintervention (T1), and at four weeks after intervention (T2). The variables of RAR and LER were derived using nonparametric analysis. We found a significant time effect on the intradaily variability (IV) of RAR at T2 with respect to T0 (p=0.039), indicating reduced IV of RAR at four weeks after personalized light intervention regardless of blue-enriched light intervention. There was a time effect on the IV of LER at T1 with respect to T0 (p=0.052), indicating a reduced tendency in the IV of LER immediately after intervention. Our personalized light intervention, regardless of blue-enriched light source, could be useful in alleviating fragmentation of RAR and LER in AD patients.

Circadian disturbances and frailty risk in older adults

Frailty is characterized by diminished resilience to stressor events. It is associated with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates ~24-h rhythms in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1000 older adults who had been followed annually for up to 16 years. We found that decreased rhythm strength, reduced stability, or increased variation were associated with a higher risk of incident frailty and faster progress of frailty over time. Perturbed circadian rest-activity rhythms may be an early sign or risk factor for frailty in older adults.

Abstract 13353: Sleep Health Phenotypes Predict Symptoms, Cognitive Function, and Adverse Events in Patients With Heart Failure

Introduction: Poor sleep contributes to outcomes in heart failure (HF). Phenotypes reflecting multi-dimensional sleep health may better predict outcomes and support more precise interventions than single measures, but few studies have used this approach. Aims: 1) Describe phenotypes of sleep health and 2) Evaluate whether sleep health phenotypes predict symptoms, cognitive function, and time to first hospitalization and emergency department (ED) visits among HF patients. Methods: We performed secondary analysis of a randomized controlled trial of cognitive behavioral therapy for insomnia compared with HF self-management education with HF patients. We measured sleep [rest-activity rhythms, sleep duration, and efficiency (2-week wrist actigraphy/follow-ups); insomnia; CPAP use; and daytime sleepiness (Epworth Scale)]; perceived stress; fatigue; anxiety; depression; pain; and cognitive ability (Patient-Reported Outcomes Measurement System: PROMIS) at baseline and 3, 6, and 12 months post-intervention and tracked hospitalizations and ED visits. We used K-means clustering to identify sleep phenotypes and generalized linear mixed models and Cox models to predict outcomes, adjusted for demographic factors. Results: Among 166 participants (M age = 63.2 (SD = 12.8) years; 57% female; 23% NYHA Class 3/4 HF; 35% EF less than 45%), there were 4 phenotypes [poor sleep (14%); short sleep/high sleep efficiency (39%); long sleep/low sleep efficiency (25%); and healthy sleep (21%)] at baseline. The healthy sleep group was older and had lower BMIs and less comorbidity and had better outcomes compared to all other phenotypes. In particular, this group had better fatigue (-2.43±0.87), pain (-1.86±1.05), anxiety (-1.50±0.89), stress (-1.46±0.69), and cognitive ability (1.76±0.80) than the poor sleep group. The poor sleep group had shorter time to adverse events compared to the other phenotypes (Hazard ratios of 0.41 to 0.56 for hospitalizations and 0.35 to 0.60 for ED visits). Conclusions: Multidimensional aspects of sleep predict HF outcomes and may improve on prediction with single measures. Future tailored sleep interventions focused on phenotypes may more precisely improve outcomes among HF patients than traditional approaches.

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.

Isolated REM sleep behavior disorder is associated with altered 24-h rest-activity measures

IntroductionIsolated 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 progressing to Parkinson's disease or dementia with Lewy bodies. Disruption of rest-activity patterns, 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-h activity would indicate greater fragmentation and variability in patients with iRBD relative to matched healthy controls.Materials and methodsPatients with iRBD (N = 38) had 24-h activity monitored for (mean ± SD) 24.6 ± 8.8 days using an Axivity wrist-worn accelerometer. Age, sex, and body mass index matched healthy older adults (N = 119) were selected as controls. Raw accelerometer data were processed and nonparametric and cosinor measures of 24-h activity were calculated. Functional principal component analyses (fPCA) were applied to detect differences in 24-h activity patterns.ResultsCompared to matched controls, individuals with iRBD had significantly lower cosine amplitude, mesor, and activity during their most active 10 hours, reflecting overall lower levels of activity and disrupted activity. They also had significantly increased movement during the night (L5). FPCA indicated that decreased daytime and increased nighttime activity may explain overall differences observed in iRBD.ConclusionMultiple metrics of rest-activity rhythms support the hypothesis that 24-h activity measures are altered in iRBD. This dysfunction may reflect degeneration of sleep-wake regulating circuits, representing a symptom of iRBD and indicating the early stages of Lewy body disease.

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.

Association between Acute Respiratory Distress Syndrome Due to COVID-19 and Long-Term Sleep and Circadian Sleep-Wake Disorders.

Current studies agree on the impact of sleep and circadian rest-activity rhythm alterations in acute respiratory distress syndrome (ARDS) survivors. However, research on the duration of this impact is scarce. In this study, we evaluate the impact of ARDS on the sleep and circadian rest-activity rhythm of COVID-19 survivors twelve months after hospital discharge. This is a prospective study including COVID-19 survivors with and without ARDS during hospitalization. Data was collected four and twelve months after hospital discharge. The interventions included one-week wrist actigraphy and a home sleep apnea test (HSAT), and evaluations were conducted according to the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). Fifty-two patients were evaluated (ARDS = 31 and non-ARDS = 21); they had a median age of 49.0 [39.0;57.2] years and 53.8% were male. After twelve months, 91.3% presented poor sleep quality, 58.7% presented insomnia, 50% presented daytime somnolence, and 37% presented comorbid insomnia and obstructive sleep apnea (COMISA). No significant improvement was observed in relation to sleep or the circadian rest-activity rhythm between four and twelve months. A tendency of poor sleep quality, insomnia, daytime somnolence, and COMISA was observed. Finally, there was no significant impact on the circadian rest-activity rhythm between four and twelve months or between the groups.

U.S. Adolescent Rest-Activity patterns: insights from functional principal component analysis (NHANES 2011–2014)

BackgroundSuboptimal rest-activity patterns in adolescence are associated with worse health outcomes in adulthood. Understanding sociodemographic factors associated with rest-activity rhythms may help identify subgroups who may benefit from interventions. This study aimed to investigate the association of rest-activity rhythm with demographic and socioeconomic characteristics in adolescents.MethodsUsing cross-sectional data from the nationally representative National Health and Nutrition Examination Survey (NHANES) 2011–2014 adolescents (N = 1814), this study derived rest-activity profiles from 7-day 24-hour accelerometer data using functional principal component analysis. Multiple linear regression was used to assess the association between participant characteristics and rest-activity profiles. Weekday and weekend specific analyses were performed in addition to the overall analysis.ResultsFour rest-activity rhythm profiles were identified, which explained a total of 82.7% of variance in the study sample, including (1) High amplitude profile; (2) Early activity window profile; (3) Early activity peak profile; and (4) Prolonged activity/reduced rest window profile. The rest-activity profiles were associated with subgroups of age, sex, race/ethnicity, and household income. On average, older age was associated with a lower value for the high amplitude and early activity window profiles, but a higher value for the early activity peak and prolonged activity/reduced rest window profiles. Compared to boys, girls had a higher value for the prolonged activity/reduced rest window profiles. When compared to Non-Hispanic White adolescents, Asian showed a lower value for the high amplitude profile, Mexican American group showed a higher value for the early activity window profile, and the Non-Hispanic Black group showed a higher value for the prolonged activity/reduced rest window profiles. Adolescents reported the lowest household income had the lowest average value for the early activity window profile.ConclusionsThis study characterized main rest-activity profiles among the US adolescents, and demonstrated that demographic and socioeconomic status factors may shape rest-activity behaviors in this population.

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

Blue light exposure-dependent improvement in robustness of circadian rest-activity rhythm in aged rats.

The aging effects on circadian rhythms have diverse implications including changes in the pattern of rhythmic expressions, such as a wide fragmentation of the rhythm of rest-activity and decrease in amplitude of activity regulated by the suprachiasmatic nucleus (SCN). The study of blue light on biological aspects has received great current interest due, among some aspects, to its positive effects on psychiatric disorders in humans. This study aims to evaluate the effect of blue light therapy on the SCN functional aspects, through the evaluation of the rest-activity rhythm, in aging rats. For this, 33 sixteen-months-old male Wistar rats underwent continuous records of locomotor activity and were exposed to periods of 6 hours of blue light during the first half of the light phase (Zeitgeber times 0-6) for 14 days. After this, the rats were maintained at 12h:12h light:dark cycle to check the long-term effect of blue light for 14 days. Blue light repeated exposure showed positive effects on the rhythmic variables of locomotor activity in aged rats, particularly the increase in amplitude, elevation of rhythmic robustness, phase advance in acrophase, and greater consolidation of the resting phase. This effect depends on the presence of daily blue light exposure. In conclusion, our results indicate that blue light is a reliable therapy to reduce circadian dysfunctions in aged rats, but other studies assessing how blue light modulates the neural components to modulate this response are still needed.

Aspects of Rest-Activity Rhythms Associated With Behavioral and Psychological Symptoms in Moderate and Severe Dementia: Results of a Cross-sectional Analysis.

Disturbances in rest-activity rhythms (RAR) are commonly observed in patients with dementia; however, the influence thereof on behavioral and psychological symptoms of dementia (BPSD) remains unexplored. This study aimed to determine whether there is an association between RAR and BPSD among patients with moderate and severe dementia. RAR analyses of 64 participants were performed using actigraphy. BPSD was assessed using the Neuropsychiatric Inventory-Nursing Home (NPI-NH) scale, and other clinical variables were assessed by the Mini-Mental State Examination, Cognitive Test for Severe Dementia, and Hyogo Activities of Daily Living Scale. Correlations among RAR, sleep time, and BPSD were analyzed. A stepwise multiple linear regression analysis was conducted to examine the association of RAR and sleep time with BPSD. The demographic variables were also adjusted. Variables were compared between two groups with aberrant and nonaberrant activity peak timing. Correlation analysis showed that longer maximum durations of activity and shorter daytime sleep were associated with higher NPI-NH scores. Stepwise multiple linear regression analysis showed that maximum activity duration predicted the NPI-NH score after adjustment for the demographic variables. There was no significant difference in any variables between the groups with aberrant and nonaberrant activity peak timing. RAR is associated with BPSD in moderate-to-severe dementia, which should be considered with regard to treatment.

Circadian rest-activity rhythms and cognitive decline and impairment in older Chinese adults: A multicohort study with prospective follow-up

BackgroundThe associations between rest-activity rhythms and cognitive health are inconclusive. The potential changes in rest-activity rhythms in older people with mild cognitive impairment (MCI) remains unclear. This study aimed to examine the association between rest-activity rhythms and cognitive health across different outcome measures in older Chinese people. MethodsA total of 710 community-dwelling participants (average age 81.1 ± 5.2 years) from two cohort studies. Wrist-worn accelerometer data was used to estimate the circadian rest-activity rhythms at baseline. Cognitive function was assessed and clinical diagnosis was made at baseline and follow-up. The two-way Analysis of Co-variance was used to compare the differences in rest-activity rhythms across participants with cognitively normal, MCI and Alzheimer's disease (AD). Logistic regression models were used to investigate the association between rest-activity rhythms and incidence of cognitive decline and impairment in a 4-year prospective follow-up of cognitively normal individuals. ResultsThere was a progressive trend of lower relative amplitude and higher activity level during the least active 5 h across participants with cognitively normal, MCI and Alzheimer's disease (AD). Among the cognitively normal participants, lower relative amplitude at baseline was associated with a greater risk of cognitive decline (per 1 SD decrease, odds ratio 1.66 [95 %CI 1.13–2.45]) and increased incidence of MCI or AD (per 1 SD decrease, 1.68 [1.12–2.50]). ConclusionsLower relative amplitude could potentially serve as a robust biomarker of cognitive decline and impairment. Further studies could evaluate the potential benefits of interventions associated with rest-activity relative amplitude to prevent or delay the progression of AD.

Alignment Between 24-h Light-Dark and Activity-Rest Rhythms Is Associated With Diabetes and Glucose Metabolism in a Nationally Representative Sample of American Adults.

The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations. The analysis included ∼7,000 adults (aged 20-80 years) from the National Health and Nutrition Examination Survey (NHANES) (2011-2014) with actigraphy-measured, multiday, 24-h activity and light data. We used phasor analysis to derive phasor magnitude and phasor angle, which measures coupling strength and phase difference between the activity-rest and light-dark cycles, respectively. We used multinomial logistic regression and multiple linear regression to study phasor magnitude and phasor angle in relation to diabetes (primary outcome) and multiple secondary biomarkers of glycemic control. Lower alignment strength (i.e., a shorter phasor magnitude) and more delayed activity relative to the light cycle (i.e., a larger phasor angle) were both associated with diabetes. Specifically, compared with individuals in the quintiles indicating the most proper alignment (Q5 for phasor magnitude and Q1 for phasor angle), those in the quintiles with the most impaired alignment had a >70% increase in the odds of diabetes for phasor magnitude (odds ratio 1.76 [95% CI 1.39, 2.24]) and for phasor angle (1.73 [1.34, 2.25]). Similar associations were observed for biomarkers for glucose metabolism. The results were generally consistent across diverse sociodemographic and obesity groups. The alignment pattern between 24-h activity-rest and light-dark cycles may be a critical factor in metabolic health.

Circadian misalignment alters resting-state functional connectivity of the salience network in rotating shift workers.

This study compared resting-state functional connectivity (rsFC) of the salience network (SN) between rotating shift workers (RSWs) and controls. Furthermore, we examined whether rsFC of the SN was correlated with sleep, emotion, cognition, and attention. The 60 RSWs and 57 controls enrolled in this study completed self-report questionnaires and sleep diaries to assess subjective sleep quality, and polysomnography and actigraphy to evaluate objective sleep and 24-hour rest-activity rhythm parameters. The participants also underwent resting-state functional magnetic resonance imaging and structural T1 scans. We performed a seed-based rsFC analysis of the SN using the anterior cingulate cortex (ACC) and anterior insula (AI) as seed regions. Furthermore, AI and ACC rsFC were compared in RSWs and controls, and we analyzed correlations between rsFC and variables of interest showing significant group differences. Compared with controls, RSWs showed reduced rsFC between the ACC and right insula, and increased rsFC of the ACC with the left occipital lobe and right superior frontal gyrus extending to the supplementary motor area (SFG/SMA). Moreover, RSWs showed reduced rsFC between the right AI and right superior parietal lobule (SPL). Finally, rsFC between the ACC and right AI was correlated with 24-hour rest-activity rhythmicity. Although RSWs did not show sleep disturbance, emotional distress, cognitive impairment, or attention deficits, alterations of right insula, left occipital lobe, right SFG/SMA, and right SPL rsFC in the SN indicate that impairments in salience detection and top-down attentional control may emerge in shift workers over time.

Chronic jet lag reduces motivation and affects other mood-related behaviors in male mice.

Introduction: The circadian system regulates various physiological processes such as sleep-wake cycles, hormone secretion, metabolism, and the reaction to both natural and drug-based rewards. Chronic disruption of the circadian system caused by unsteady synchronization with light-dark (LD) schedules, such as advancing chronic jet lag (CJL), leads to adverse physiological effects and pathologies, and is linked with changes in mood and depressive behaviors in humans and rodent models. Methods: C57BL/6J male mice were subjected to circadian disruption through phase advances of 6h every 2days (CJL +6/2). Mice under 12:12-h LD cycle were used as controls. After 8weeks under these conditions, a battery of behavioral tests was performed to assess if mood-related behaviors were affected. Results: Compared to controls under 24h LD cycles, mice under CJL presented desynchronization of activity-rest rhythms that led to several behavioral impairments, including a decrease in motivation for food reward, and an increase in anxiety, anhedonia, and depressive-like behavior. Conclusion: Chronic circadian disruption, caused by an experimental CJL protocol, affects mood-related and reward-related behaviors in mice. Understanding the importance of the circadian system and its potential role for disruption due to CJL is important for maintaining good health and well-being.