Rest-activity Patterns Research Articles

0647 Rest-activity pattern in Major depressive disorder - a case control study

Abstract Introduction Disruption of rest-activity pattern are important behavioral manifestations in patients with major depressive disorder (MDD). Actigraphy provides accessible and objective measurement on physical activity, sleep, and circadian rhythm, but it was not widely used in studying patients with MDD, especially among Asian population. Methods Rest-activity pattern was recorded by Actiwatch Spectrum Plus/PRO for 7 continuous days. Physical activity and sleep estimation was processed by Philips Actiware software 6. Circadian rhythm characteristics were generated by using the “cosinor” and “nparACT” packages in R to perform the cosinor and nonparametric analysis respectively. Results A total of 70 MDD subjects, and 59 age- and sex-comparable controls were included in the actigraphy data analysis. The mean age of MDD subjects was 51.24 ± 10.39 years, and 71.4% of MDD subjects were female. Of these MDD subjects, 54.3% were unremitted for their depressive illness. For sleep and circadian features, MDD subjects had higher Insomnia Severity Index (ISI score, MDD: 10.29 ± 5.70; controls: 6.05 ± 5.20, P < 0.001) and lower reduced Morningness-Eveningness questionnaire (rMEQ score, MDD: 13.19 ± 4.62; controls: 16.07 ± 3.28, P < 0.001) than controls. The percentage of mobility measured by actigraphy was significantly lower in MDD patients than controls (MDD: 58.58%; controls: 62.27%, P < 0.001), albeit the difference only occurred during rest period. MDD subjects had later acrophase (P = 0.024), M10 midpoint (P = 0.040) and a trend of delayed sleep midpoint (P = 0.076) and longer sleep duration (P = 0.067) than controls. When the comparison was performed among three groups, unremitted MDD subjects showed a higher intra-individual variability of sleep midpoint than remitted MDD group (P = 0.021) and higher intra-individual variability for sleep duration than controls (P = 0.016). Conclusion MDD subjects had increased insomnia and eveningness than controls, which was supported by the acitgraphy data at which MDD had a tendency of longer major rest interval and delayed circadian phase. Unremitted MDD subjects showed a higher intra-individual variability of sleep midpoint and sleep duration. These actigraphy parameters may be useful markers for phenotyping and monitoring of MDD. Support (if any)

0712 Improved Circadian Rest-Activity Patterns after Treatment with PAP therapy in the Patient with Idiopathic RBD and Comorbid OSA

Abstract Introduction Several studies suggest that sleep and circadian rhythm disruptions, and physical activity changes may serve as risk factors for the occurrence of Parkinson’s disease and its prodromal features. Obstructive sleep apnea (OSA) is commonly found in patients with RBD. The comorbid OSA is associated with non-motor symptoms, including daytime sleepiness, cogntive decline and autonomic nervous system dysfunction. Therefore, we investigated whether circadian rest-activity patterns and RBD-related symptoms will be improved after positive airway pressure (PAP) therapy in patients who had iRBD with comorbid OSA. Methods Seven patients were diagnosed as iRBD with OSA (AHI ≥ 10) confirmed by video-polysomnography. The patients wore actigraphy devices for 14 consecutive days befor and after PAP therapy for 3 months. The mean motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphic data. Non-parametric circadian rhythm activity including inter-daily stability(IS), intra-daily variability, least 5 average, most 10 average and relative amplitude were anlayzed. In addition, we obtainted the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I). Results Four of 7 patients had good compliance of PAP usage (average usage > 4hr during sleep), and three patients had poor compliance of PAP usage. In good compliance group, score of RBD-3M decreased ( p=0.029) and value of IS were increased (p=0.029 ) significantly. Also, 3 of 4 patients answered “Very much improved or much improved” in a questionnaire of CGI. In poor comliance group, there was no any significant change in all values. In addition, only one patient answered “ much imrpoved” and two patients answered “minimally improved” in CGI. Conclusion The PAP treatment of OSA in iRBD can be role as a lifestyle modifier that improves circadian rest-activity patterns and, it may be of value as a disease-modifying effect of behavioral or lifestyle changes that have been reported to be associated with decreased risk of neurodegenerative disorder. We will continue enroll the data and will investigate not only improvement of circadian rhythm, but also decreasing of motor activities during sleep after PAP therapy. Support (if any)

Circadian Factors in Stroke: A Clinician's Perspective.

Stroke remains one of the leading causes of mortality and long-term and permanent disability worldwide despite technological innovations and developments in pharmacotherapy. In the last few decades, the growing data have evidenced the role of the circadian system in brain vulnerability to damage, the development and evolution of stroke, and short-term and long-term recovery. On the other hand, the stroke itself can affect the circadian system via direct injury of specific brain structures involved in circadian regulation (i.e., hypothalamus, retinohypothalamic tracts, etc.) and impairment of endogenous regulatory mechanisms, metabolic derangement, and a neurogenic inflammatory response in acute stroke. Moreover, the disruption of circadian rhythms can occur or exacerbate as a result of exogenous factors related to hospitalization itself, the conditions in the intensive care unit and the ward (light, noise, etc.), medication (sedatives and hypnotics), and loss of external factors entraining the circadian rhythms. In the acute phase of stroke, patients demonstrate abnormal circadian variations in circadian biomarkers (melatonin, cortisol), core body temperature, and rest-activity patterns. The approaches aimed at the restoration of disrupted circadian patterns include pharmacological (melatonin supplementation) and non-medication (bright light therapy, shifting feeding schedules, etc.) interventions; however, their effects on short- and long-term recovery after stroke are not well understood.

0841 Feasibility of Actigraphy during a Daytime Bright Pilot Study in the Medical ICU

Abstract Introduction Medical intensive care unit (MICU) light patterns are inadequate for proper circadian alignment. Sleep disruption and circadian misalignment are observed in MICU patients and adversely impact patient outcomes. We sought to establish the feasibility of using longitudinal actigraphy to measure diurnal rest-activity patterns, as a in the context of a pilot study evaluating daytime bright light (DBL). In an exploratory manner, we analyzed diurnal rest-activity characteristics. Methods Patients >50 years admitted to the MICU without pre-existing circadian disruption were enrolled. An actigraph was placed (wrist) on study day 1 (D1) and remained for up to 5 days. DBL exposure (>1200 lux, 5000K) began at 09:00 on D2 and continued until D5 (varied lengths of exposure among patients). Actigraphy feasibility was assessed via (1) total recording duration and (2) proportion of total recording with activity data (e.g., proportion of epochs on wrist with data capture). In an exploratory analysis, we evaluated rest-activity characteristics from D1 and D2 for fit with gamma distribution cosinor analysis. Characteristics included ratio of day/total activity, mesor (midline estimation statistic of circadian rhythm), and circadian quotient (normalized amplitude/mesor). Results Thirteen of fourteen enrolled patients completed actigraphy. Mean (SD) age was 74 (11) years. Mean APACHE II illness severity score was 21 (4). Patients had a mean 3.7 (1.3) days of actigraphy recording and a mean activity data proportion of 92% (16%). There were only two reports of temporary actigraph removal related to patient care. All actigraphy patients had fit using cosinor analysis. D1 median (IQR) day/total ratio was 0.76 (0.68,0.82), mesor was 10.31 (6.36,13.00), and circadian quotient was 0.82 (0.48,0.99). D2 (after DBL start) median (IQR) day/total ratio was 0.76 (0.64,0.78), mesor was 11.90 (8.97,15.83), and circadian quotient was 0.89 (0.65,0.95). Conclusion Here we demonstrate the feasibility of actigraphy as a measure of diurnal rest-activity patterns in MICU patients based on successful collection and analysis of data in all patients. While cohort size remains a limitation of this study, Actigraphic rest-activity patterns are being explored in an ongoing RCT evaluating the impact of DBL versus usual light exposure on circadian rhythms in critical illness. Support (if any) K23HL138229, AASM Foundation

Smartphone Keyboard Interaction Monitoring as an Unobtrusive Method to Approximate Rest-Activity Patterns: Experience Sampling Study Investigating Interindividual and Metric-Specific Variations

Sleep is an important determinant of individuals' health and behavior during the wake phase. Novel research methods for field assessments are required to enable the monitoring of sleep over a prolonged period and across a large number of people. The ubiquity of smartphones offers new avenues for detecting rest-activity patterns in everyday life in a noninvasive an inexpensive manner and on a large scale. Recent studies provided evidence for the potential of smartphone interaction monitoring as a novel tracking method to approximate rest-activity patterns based on the timing of smartphone activity and inactivity throughout the 24-hour day. These findings require further replication and more detailed insights into interindividual variations in the associations and deviations with commonly used metrics for monitoring rest-activity patterns in everyday life. This study aimed to replicate and expand on earlier findings regarding the associations and deviations between smartphone keyboard-derived and self-reported estimates of the timing of the onset of the rest and active periods and the duration of the rest period. Moreover, we aimed to quantify interindividual variations in the associations and time differences between the 2 assessment modalities and to investigate to what extent general sleep quality, chronotype, and trait self-control moderate these associations and deviations. Students were recruited to participate in a 7-day experience sampling study with parallel smartphone keyboard interaction monitoring. Multilevel modeling was used to analyze the data. In total, 157 students participated in the study, with an overall response rate of 88.9% for the diaries. The results revealed moderate to strong relationships between the keyboard-derived and self-reported estimates, with stronger associations for the timing-related estimates (β ranging from .61 to .78) than for the duration-related estimates (β=.51 and β=.52). The relational strength between the time-related estimates was lower, but did not substantially differ for the duration-related estimates, among students experiencing more disturbances in their general sleep quality. Time differences between the keyboard-derived and self-reported estimates were, on average, small (<0.5 hours); however, large discrepancies were also registered for quite some nights. The time differences between the 2 assessment modalities were larger for both timing-related and rest duration-related estimates among students who reported more disturbances in their general sleep quality. Chronotype and trait self-control did not significantly moderate the associations and deviations between the 2 assessment modalities. We replicated the positive potential of smartphone keyboard interaction monitoring for estimating rest-activity patterns among populations of regular smartphone users. Chronotype and trait self-control did not significantly influence the metrics' accuracy, whereas general sleep quality did: the behavioral proxies obtained from smartphone interactions appeared to be less powerful among students who experienced lower general sleep quality. The generalization and underlying process of these findings require further investigation.

Actigraphy-derived physical activity levels and circadian rhythm parameters in patients with psoriatic arthritis: relationship with disease activity, mood, age and BMI.

Psoriatic arthritis (PsA) is associated with sleep disturbance, depression and a lifetime risk of obesity and cardiovascular disease. To date, there have been no studies investigating the relationship between objectively-measured physical activity (PA) levels and circadian rhythm disturbance with disease activity, daily symptoms and mood in patients with PsA. This pilot study aimed to investigate the relationship between disease activity, daily symptoms and mood on PA and circadian rhythm in PsA. A prospective cohort study recruiting adults with PsA from rheumatology clinics at a single centre in the UK. Participants wore an actigraph and recorded their symptoms and mood on a daily basis via a smartphone app for 28 days. Time spent in sedentary, light and moderate-to-vigorous physical activity (MVPA) and parameters reflecting the circadian rhythm of the rest-activity pattern were derived. This included the onset time of the least active 5-h (L5) and most active 10-h (M10) daily consecutive periods and the relative amplitude (RA). The relationship factors between baseline clinical status, daily symptoms, PA and circadian measures were examined using linear mixed effect regression models. Nineteen participants (8/19 female) were included. Participants with active PsA spent 63.87 min (95% CI: 18.5-109.3, p = 0.008) more in inactivity and 30.78 min (95% CI: 0.4-61.1, p = 0.047) less in MVPA per day compared to those in minimal disease activity (MDA). Age, body mass index and disease duration were also associated with PA duration. Participants with worse functional impairment had an M10 onset time 1.94 h (95% CI: 0.05-3.39, p = 0.011) later than those with no reported functional impairment. No differences were detected for L5 onset time or RA. Higher scores for positive mood components such as feeling energetic, cheerful and elated were associated with less time in inactivity and greater time spent in MVPA overall. Our study highlights differences in PA and circadian rest-activity pattern timing based on disease activity, disability and daily mood in PsA. Reduced PA levels in patients with active disease may contribute to the observed increased risk of cardiovascular and metabolic sequelae, with further studies exploring this need.

Sleep and Rest-Activity Rhythms in Recovering Patients with Severe Concurrent Mental and Substance Use Disorder: A Pilot Study

Objective: Mental health and substance use disorders are commonly associated with disrupted sleep and circadian rest-activity rhythms. How these disorders in combination relate to sleep and circadian organization is not well studied. We provide here the first quantitative assessment of sleep and rest-activity rhythms in inpatients with complex concurrent disorders, taking into account categories of substance use (stimulant vs. stimulant and opioid use) and psychiatric diagnosis (psychotic disorder and mood disorder). We also explore how sleep and rest-activity rhythms relate to psychiatric functioning. Methods: A total of 44 participants (10 female) between the age of 20–60 years (median = 29 years) wore wrist accelerometers over 5–70 days and completed standardized questionnaires assessing chronotype and psychiatric functioning (fatigue, psychiatric symptom severity, and impulsiveness). To examine potential influences from treatment, we computed (1) length of stay; (2) days of abstinence from stimulants and opioids as a measure of withdrawal; and (3) a sedative load based on prescribed medications. Results: Participants exhibited a sustained excessive sleep duration, frequent nighttime awakenings, and advanced rest-activity phase related to sedative load. Sleep disruptions were elevated in participants with a history of opioid use. Patients with a psychotic disorder showed the longest sleep and most fragmented and irregular rest-activity patterns. Non-parametric circadian rhythm analysis revealed a high rhythm amplitude by comparison with population norms, and this was associated with greater psychiatric symptom severity. Psychiatric symptom severity was also associated with greater fatigue and later MCTQ chronotype. Conclusions: This pilot study provides initial information on the prevalence and severity of sleep and circadian rhythm disturbances in individuals with severe concurrent disorders. The results underline the need for further studies to start to understand the role of sleep in the disease and recovery process in this understudied population.

Mating disrupts morning anticipation in Drosophila melanogaster females.

After mating, the physiology of Drosophila females undergo several important changes, some of which are reflected in their rest-activity cycles. To explore the hypothesis that mating modifies the temporal organization of locomotor activity patterns, we recorded fly activity by a video tracking method. Monitoring rest-activity patterns under light/dark (LD) cycles indicated that mated females lose their ability to anticipate the night-day transition, in stark contrast to males and virgins. This postmating response is mediated by the activation of the sex peptide receptor (SPR) mainly on pickpocket (ppk) expressing neurons, since reducing expression of this receptor in these neurons restores the ability to anticipate the LD transition in mated females. Furthermore, we provide evidence of connectivity between ppk+ neurons and the pigment-dispersing factor (PDF)-positive ventral lateral neurons (sLNv), which play a central role in the temporal organization of daily activity. Since PDF has been associated to the generation of the morning activity peak, we hypothesized that the mating signal could modulate PDF levels. Indeed, we confirm that mated females have reduced PDF levels at the dorsal protocerebrum; moreover, SPR downregulation in ppk+ neurons mimics PDF levels observed in males. In sum, our results are consistent with a model whereby mating-triggered signals reach clock neurons in the fly central nervous system to modulate the temporal organization of circadian behavior according to the needs of the new status.

Technological infrastructure, sleep, and rest-activity patterns in a Kaqchikel Maya community.

Sleep duration, quality, and rest-activity pattern-a measure for inferring circadian rhythm-are influenced by multiple factors including access to electricity. Recent findings suggest that the safety and comfort afforded by technology may improve sleep but negatively impact rest-activity stability. According to the circadian entrainment hypothesis, increased access to electric lighting should lead to weaker and less uniform circadian rhythms, measured by stability of rest-activity patterns. Here, we investigate sleep in a Maya community in Guatemala who are in a transitional stage of industrialization. We predicted that (i) sleep will be shorter and less efficient in this population than in industrial settings, and that (ii) rest-activity patterns will be weaker and less stable than in contexts with greater exposure to the natural environment and stronger and more stable than in settings more buffered by technologic infrastructure. Our results were mixed. Compared to more industrialized settings, in our study population sleep was 4.87% less efficient (78.39% vs 83.26%). We found no significant difference in sleep duration. Rest-activity patterns were more uniform and less variable than in industrial settings (interdaily stability = 0.58 vs 0.43; intradaily variability = 0.53 vs 0.60). Our results suggest that industrialization does not inherently reduce characteristics of sleep quality; instead, the safety and comfort afforded by technological development may improve sleep, and an intermediate degree of environmental exposure and technological buffering may support circadian rhythm strength and stability.

Abstract 10895: Actigraphy-Derived Rest-Activity Rhythms Are Associated With Metabolic Markers and Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Individual behaviors in the 24h rest-activity cycle have been linked to cardiometabolic health (CMH). Studies that integrate the overall multidimensional pattern of 24-h rest-activity rhythms (RAR) and evaluate its unique relation with CMH and type 2 diabetes (T2D) are limited. Hypothesis: Disrupted RAR are associated with poorer glycemic control and T2D. Methods: Participants were n=2127 adults (mean age: 69 ± 9 y, 54% women, 62% non-White) in the MESA Sleep Study (2010-13). Interdaily stability (IS), intradaily variability (IV), most active 10 h period (M10) and least active 5 h period (L5) timing and counts, and relative amplitude (RA) (defined in Table) were derived from 7-d actigraphy data using nonparametric rhythm analysis. Multivariable linear and logistic regression was used to examine cross-sectional and prospective associations with glycemic markers and T2D at baseline and after 6 y of follow-up (2016-18). Results: Higher IS (more stable sleep-wake and rest-activity patterns across days), M10 counts (more active wake period), and RA (greater overall RAR robustness) were related to lower fasting glucose, insulin, and HOMA-IR, while higher IV (more fragmented RAR, less efficient sleep) and L5 counts (less restful sleep) were related to higher levels of these metabolic markers (Table). In cross-sectional and prospective analyses, those in the highest vs. lowest quintile of IS, M10 counts, and RA had up to 75% lower odds of T2D, while being in the highest vs. lowest quintile of IV, L5 counts, and L5 midpoint (later sleep period) was associated with up to 79% higher T2D odds with evidence of a dose-response relationship (p-trend &lt;0.05 for all outcomes). Conclusions: A less robust and stable RAR, lower wake time activity, and a less restful and later sleep period are associated with T2D. Targeting the strength, timing, and regularity of rest-activity and sleep-wake patterns to enhance the rhythmicity of diurnal behaviors may enhance CMH and prevent T2D.

Seasonal variation in rest-activity patterns in barnacle geese: are measurements of activity a good indicator of sleep-wake patterns?

Sleep is a widely spread phenomenon in the animal kingdom and is thought to serve important functions. Yet, the function of sleep remains an enigma. Studies in non-model animal species in their natural habitat might provide more insight into the evolution and function of sleep. However, polysomnography in the wild may not always be an option or first choice and some studies may need to rely on rest-activity recordings as a proxy for sleep and wakefulness. In the current paper, we analyzed how accelerometry-based activity data correlate with electroencephalogram (EEG)-based sleep-wake patterns in barnacle geese under seminatural conditions across different seasons. In winter, the geese had pronounced daily rhythms in rest and activity, with most activity occurring during the daytime. In summer, activity was more spread out over the 24 h cycle. Hourly activity scores strongly correlated with EEG-determined time awake, but the strength of the correlation varied with phase of the day and season. In winter, the correlations between activity and waking time were weaker for daytime than for night-time. Furthermore, the correlations between activity and waking during daytime were weaker in winter than in summer. During daytime in winter, there were many instances where the birds were awake but not moving. Experimental sleep deprivation had no effect on the strength of the correlation between activity scores and EEG-based wake time. Overall, hourly activity scores also showed significant inverse correlation with the time spent in non-rapid eye movement (NREM) sleep. However, correlation between activity scores and time spent in REM sleep was weak. In conclusion, accelerometry-based activity scores can serve as a good estimate for time awake or even the specific time spent in NREM sleep. However, activity scores cannot reliably predict REM sleep and sleep architecture.

Associations of 24-Hour Light Exposure and Activity Patterns and Risk of Cognitive Impairment and Decline in Older Men: The MrOS Sleep Study.

Older men with the worse alignment of activity and light may have lower levels of cognition and increased rates of cognitive decline. This cohort consisted of 1 036 older men (81.1 ± 4.6 years) from the MrOS Sleep Study (2009-2012). Light and activity levels were gathered by wrist actigraphy. Phasor analysis was used to quantify the alignment of light-dark and rest-activity patterns (magnitude) and their temporal relationship (angle). Global cognitive function (Modified Mini-Mental State examination [3MS]) and executive function (Trails B test) were measured, then repeated 4.2 ± 0.8 years later. Linear regression models examined the associations of phasor magnitude and angle with cognition and cognitive decline. Models were adjusted for age, clinic, race, education, and season. Smaller phasor magnitude (worse aligned light and activity patterns) was associated with lower initial level and increased decline in executive function. Compared to those with higher phasor magnitude, those with lower magnitude took an average of 11.1 seconds longer to complete the Trails B test (quartile 1 vs quartile 4, p = .02). After follow-up, Trails B completion time increased an average of 5.5 seconds per standard deviation decrease in phasor magnitude (95% confidence interval [CI] 0.7-10.4, p = .03). There were no associations with phasor angle, and none with magnitude and global cognition (3MS). Among older men, worse alignment of light and activity patterns was associated with worse initial performance and increased decline in executive function, but not related to global cognition. Interventions that improve the alignment of light and activity may slow cognitive decline in older adults.

Sleep and circadian rest-activity pattern of critical COVID-19 survivors in the long-term: a 6-month follow-up study

Sleep and circadian rest-activity pattern of critical COVID-19 survivors in the long-term: a 6-month follow-up study

Sleep health and the circadian rest-activity pattern four months after COVID-19.

ABSTRACTObjective:To describe the prevalence and severity of sleep disorders and circadian alterations in COVID-19 patients four months after the acute phase of the disease. Methods:This was a cross-sectional observational prospective study of patients with mild COVID-19, moderate COVID-19 (requiring hospitalization but no mechanical ventilation), or severe COVID-19 (with ARDS) four months after the acute phase of the disease. All patients underwent a home sleep apnea test and seven-day wrist actigraphy, as well as completing questionnaires to assess sleep quality and mental health. Differences among the three groups of patients were evaluated by ANOVA and the chi-square test. Results:A total of 60 patients were included in the study. Of those, 17 were in the mild COVID-19 group, 18 were in the moderate COVID-19 group, and 25 were in the severe COVID-19 group. Sleep quality, as assessed by satisfaction, alertness, timing, efficiency, and duration scale scores, was found to be impaired in all three groups, which also had a high prevalence of unhealthy sleep, as assessed by the Pittsburgh Sleep Quality Index. The prevalence of insomnia was increased in all three groups, as assessed by the Insomnia Severity Index. The home sleep apnea test showed that the overall prevalence of obstructive sleep apnea was 60%, and seven-day wrist actigraphy showed that total sleep time was < 7 h in all three groups. Changes in quality of life and in the circadian rest-activity pattern were observed in all three groups. Conclusions:Sleep-related symptoms, changes in the circadian rest-activity pattern, and impaired mental health appear to be common in COVID-19 patients four months after the acute phase of the disease, severe COVID-19 being associated with a higher prevalence of obstructive sleep apnea.

A biobehavioral intervention to enhance recovery following hematopoietic cell transplantation: Protocol for a feasibility and acceptability randomized control trial

BackgroundInsomnia, fatigue, and depression are among the most persistent and distressing concerns for hematologic cancer patients recovering from hematopoietic cell transplantation (HCT). This study will evaluate a novel behavioral intervention, Restoring Sleep and Energy after Transplant (ReSET), designed to alleviate insomnia, fatigue, and depression by improving rest-activity patterns. Evidence-based behavioral strategies to improve nighttime sleep and increase non-sedentary daytime activity will be combined to optimize 24-h rest-activity patterns. MethodsThe protocol herein evaluates the feasibility and acceptability of ReSET by conducting a pilot randomized controlled trial to compare the intervention with usual care. Adults undergoing HCT will be randomly assigned to ReSET or usual care. The ReSET arm will receive 3 face-to-face sessions and telephone coaching delivered in an individual format tailored to each patient. Patient-reported insomnia, fatigue, and depression will be the primary outcome measures. Actigraphy will be used to objectively quantify rest-activity patterns. Semi-structured interviews will evaluate participant satisfaction with ReSET. The goals are to determine: (1) participant satisfaction with and acceptability of the behavioral techniques; (2) facilitator fidelity and participant uptake of key intervention components; (3) ability to recruit, retain, and collect complete data from participants; (4) participant willingness to be randomized and acceptability of the control condition; and (5) validity and acceptability of the assessment strategy. ConclusionThe overarching goal is to optimize recovery following HCT with a brief, non-invasive intervention that can be implemented as a part of routine clinical care.

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

0156 Rest-activity profiles among U.S. adults in a nationally representative sample: a functional principal component analysis

Abstract Introduction The 24-hour rest and activity behaviors are fundamental human behaviors essential to health and well-being. Functional principal component analysis (fPCA) is a flexible approach for characterizing rest-activity rhythms and does not rely on a priori assumptions about the activity shape. The objective of our study is to apply fPCA to a nationally representative sample of American adults to characterize variations in the 24-hour rest-activity pattern, determine how the pattern differs according to demographic, socioeconomic and work characteristics, and examine its associations with general health status. Methods The current analysis used data from adults 25 or older in the National Health and Nutrition Examination Survey (NHANES, 2011-2014). We applied fPCA to derive profiles of the rest-activity cycle for overall, weekday and weekend activity patterns. We examined the association between each rest-activity profile in relation to age, gender, race/ethnicity, education, income and working status using multiple linear regression. We also used multiple logistic regression to determine the relationship between each rest-activity profile and the likelihood of reporting poor or fair health. Results We identified four distinct profiles (i.e., high amplitude, early rise, prolonged activity window, biphasic pattern) that together accounted for 86.8% of total variation in the study sample. We identified numerous associations between each rest-activity profile and multiple sociodemographic characteristics. We also found evidence suggesting the associations differed between weekdays and weekends. Finally, we reported that the rest-activity profiles were associated with self-rated health. Conclusion Our study provided evidence suggesting that rest-activity patterns in human populations are shaped by multiple demographic, socioeconomic and work factors, and are correlated with health status. Support (If Any)

RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer’s disease, and normative aging

BackgroundRegulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer’s disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging.MethodsThe present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3–6 months old) and aged (9–14 months old) mice of both sexes.ResultsWe found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN.ConclusionsCollectively, this study’s findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging.

The history of sleep research and sleep medicine in Europe.

Sleep became a subject of scientific research in the second half of the 19th century. Since sleep, unlike other physiological functions, cannot be attributed to a specific organ, there was no distinct method available to study sleep until then. With the development of physiology and psychology, and a rapidly increasing knowledge of the structure and functioning of the nervous system, certain aspects of sleep became accessible to objective study. A first step was to measure responsiveness to external stimuli systematically, during sleep, allowing a first representation of the course of sleep (Schlaftiefe=sleep depth). A second method was to register continuously the motor activity across the sleep-wake cycle, which allowed the documentation in detail of rest-activity patterns of monophasic and polyphasic sleep-wake rhythms, or between day or night active animals. The central measurement for sleep research, however, became the electroencephalogram in the 1930s, which allowed observation of the sleeping brain with high temporal resolution. Beside the development of instruments to measure sleep, prolonged sleep deprivation was applied to study physiological and psychological effects of sleep loss. Another input came from clinical and neuropathological observations of patients with pronounced disorders of the sleep-wake cycle, which for the first time allowed localisation of brain areas that are essentially involved in the regulation of sleep and wakefulness. Experimental brain stimulation and lesion studies were carried out with the same aim at this time. Many of these activities came to a halt on the eve of World War II. It was only in the early 1950s, when periods with rapid eye movements during sleep were recognised, that sleep became a research topic of itself. Jouvet and his team explored the brain mechanisms and transmitters of paradoxical sleep, and experimental sleep research became established in all European countries. Sleep medicine evolving simultaneously in different countries, with early centres in Italy and France. In the late 1960s sleep research and chronobiology began to merge. In recent decades, sleep research, dream research, and sleep medicine have benefited greatly from new methods in genetic research and brain imaging techniques. Genes were identified that are involved in the regulation of sleep, circadian rhythms, or sleep disorders. Functional imaging enabled a high spatial resolution of the activity of the sleeping brain, complementing the high temporal resolution of the electroencephalogram.