Sleep-wake behaviors associated with cognitive performance in middle-aged participants of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVES: Many sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance. METHODS: The outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions. RESULTS: In individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with ∼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility. CONCLUSION: The strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition.

Behavioral-Social Rhythms and Cardiovascular Disease Risk in Retired Night Shift Workers and Retired Day Workers.

OBJECTIVE: Stability in the timing of key daily routine behaviors such as working/doing housework, sleeping, eating, and engaging in social interactions (i.e., behavioral-social rhythms) contributes to health. This study examined whether behavioral-social rhythms were associated with cardiovascular disease (CVD) risk factors in retired night shift workers and retired day workers and explored whether past night shift work exposure moderated this association. METHODS: A total of 154 retired older adults participated in this study. Multiple logistic regression models were used to examine associations between behavioral-social rhythms and CVD risk factors. Independent variables included Social Rhythm Metric (SRM)-5 score and actigraphy rest-activity rhythm intradaily variability (IV) and interdaily stability (IS). Dependent variables were metabolic syndrome prevalence and its five individual components. RESULTS: More regular behavioral-social rhythms were associated with lower odds of prevalent metabolic syndrome (SRM: odds ratio [OR] = 0.57, 95% confidence interval [CI] = 0.35-0.88; IV: OR = 4.00, 95% CI = 1.86-8.58; IS: OR = 0.42, 95% CI = 0.24-0.73) and two of its individual components: body mass index (SRM: OR = 0.56, 95% CI = 0.37-0.85; IV: OR = 2.84, 95% CI = 1.59-5.07; IS: OR = 0.42, 95% CI = 0.26-0.68) and high-density lipoprotein cholesterol (SRM: OR = 0.49, 95% CI = 0.30-0.80; IV: OR = 2.49, 95% CI = 1.25-4.96; IS: OR = 0.35, 95% CI = 0.19-0.66). Past shift work history did not moderate the association between behavioral-social rhythms and metabolic syndrome. CONCLUSIONS: Behavioral-social rhythms were related to CVD risk factors in retired adults regardless of prior night shift work exposure. Older retired workers may benefit from education and interventions aiming to increase behavioral-social rhythm regularity.

Rest-activity rhythm disruption and metabolic health in schizophrenia: a cross-sectional actigraphy study of community-dwelling people living with schizophrenia and non-psychiatric comparison participants.

STUDY OBJECTIVES: People living with schizophrenia (PLWS) have increased physical comorbidities and premature mortality which may be linked to dysregulated rest-activity rhythms (RARs). This study aimed to compare RARs between PLWS and non-psychiatric comparison participants (NCs); examine the relationships of RARs with age, sleep, metabolic and physical health outcomes; and, among PLWS, relationships of RARs with illness-related factors. METHODS: The study sample included 26 PLWS and 36 NCs, assessed with wrist-worn actigraphy to compute RAR variables and general sleep variables. Participants completed assessments for clinical symptoms, physical health, sleep quality, medication use, and assays for fasting glycosylated hemoglobin (HbA1c) levels. We examined group differences in RAR and sleep variables, relationships of RAR variables with metabolic and physical health measures, and, among PLWS, relationships between RAR variables and illness-related measures. RESULTS: PLWS had significantly shorter active periods, lower relative amplitude, and lower mean activity during their most active 10 hours compared to the NCs (Cohen's d=.79, .58, and .62; respectively). PLWS had poorer sleep quality, greater mean percent sleep, less wake after sleep onset, and higher total sleep time (TST) variability compared to NCs. PLWS had higher rates of antidepressant, anxiolytic, and antipsychotic medication use compared to NCs, which may have impacted sleep quality and objective sleep measures. Across both groups, more fragmented and variable RARs were associated with higher HbA1c levels (ηp2=0.10) and worse physical health (ηp2=0.21). Among PLWS, RARs were correlated with TST (rs=.789, p<0.01) and percent sleep (rs=.509, p<0.05), but not with age, sleep quality, or other illness-related factors. CONCLUSIONS: RARs provide unique information about sleep and activity for PLWS and have the potential for targeted interventions to improve metabolic health and mortality.

Stability and Volatility of Human Rest-Activity Rhythms: Insights from Very Long Actograms (VLAs).

Importance: Wrist-worn activity monitors provide biomarkers of health by non-obtrusively measuring the timing and amount of rest and physical activity (rest-activity rhythms, RARs). The morphology and robustness of RARs vary by age, gender, and sociodemographic factors, and are perturbed in various chronic illnesses. However, these are cross-sectionally derived associations from recordings lasting 4-10 days, providing little insights into how RARs vary with time. Objective: To describe how RAR parameters can vary or evolve with time (~months). Design Setting and Participants: 48 very long actograms ("VLAs", ≥90 days in duration) were identified from subjects enrolled in the STAGES (Stanford Technology, Analytics and Genomics in Sleep) study, a prospective cross-sectional, multi-site assessment of individuals > 13 years of age that required diagnostic polysomnography to address a sleep complaint. A single 3-year long VLA (author GD) is also described. Exposures/Intervention: None planned. Main Outcomes and Measures: For each VLA, we assessed the following parameters in 14-day windows: circadian/ultradian spectrum, pseudo-F statistic ("F"), cosinor amplitude, intradaily variability, interdaily stability, acrophase and estimates of "sleep" and non-wearing. Results: Included STAGES subjects (n = 48, 30 female) had a median age of 51, BMI of 29.4kg/m2, Epworth Sleepiness Scale score (ESS) of 10/24 and a median recording duration of 120 days. We observed marked within-subject undulations in all six RAR parameters, with many subjects displaying ultradian rhythms of activity that waxed and waned in intensity. When appraised at the group level (nomothetic), averaged RAR parameters remained remarkably stable over a ~4 month recording period. Cohort-level deficits in average RAR robustness associated with unemployment or high BMI (>29.4) also remained stable over time. Conclusions and Relevance: Through an exemplary set of months-long wrist actigraphy recordings, this study quantitatively depicts the longitudinal stability and dynamic range of human rest-activity rhythms. We propose that continuous and long-term actigraphy may have broad potential as a holistic, transdiagnostic and ecologically valid monitoring biomarker of changes in chronobiological health. Prospective recordings from willing subjects will be necessary to precisely define contexts of use.

Sleep-wake behavioral characteristics associated with depression symptoms: findings from the Multi-Ethnic Study of Atherosclerosis.

STUDY OBJECTIVES: To help prioritize target/groups for experimental intervention studies, we characterized cross-sectional associations between 24-hour sleep-wake measures and depression symptoms, and evaluated if similar sleep-wake-depression relationships existed in people with and without higher insomnia severity. METHODS: Participants had ≥3 days of actigraphy data (n = 1884; mean age = 68.6/SD = 9.1; 54.1% female). We extracted 18 sleep, activity, timing, rhythmicity, and fragmentation measures from actigraphy. We used individual and multivariable regressions with the outcome of clinically significant depression symptoms (Center for Epidemiologic Studies Depression Scale ≥ 16). We conducted sensitivity analyses in people with higher insomnia severity (top quartile of the Women's Health Initiative Insomnia Rating Scale total score). RESULTS: From separate models in the overall sample, the odds of having depression symptoms were higher with: later timing (e.g. activity onset time odds ratio [OR]/1 SD = 1.32; 95% confidence interval [CI]: 1.16 to 1.50), lower rhythmicity (e.g. pseudo-F OR/1 SD = 0.75; 95% CI: 0.66 to 0.85), less activity (e.g. amplitude OR/1 SD = 0.83; 95% CI: 0.72 to 0.95), and worse insomnia (OR/1 SD = 1.48, 95% CI: 1.31 to 1.68). In multivariable models conducted among people with lower insomnia severity, later timing, lower rhythmicity, and higher insomnia severity were independent correlates of depression. In people with higher insomnia symptom severity, measures of later timing were most strongly associated with depression symptoms. CONCLUSIONS: These correlative observations suggest that experimental studies are warranted to test if: broadly promoting 24-hour sleep-wake functioning reduces depression even in people without severe insomnia, and if advancing timing leads to depression symptom reductions in people with insomnia.

Efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction for Depression Symptoms and Sleep-Wake Disruption in Older and Younger Adults: Secondary Age-Stratified Analysis of a Randomized Controlled Trial.

OBJECTIVE: Perform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms. DESIGN: Secondary analysis of a randomized controlled trial with convenience age subsamples (younger (20-49 year; n = 52) versus and older (50-71 years; n = 35)). SETTING: Community mental health clinics. PARTICIPANTS: Eighty-seven adults with serious mental illness. INTERVENTION: TranS-C versus treatment as usual (TAU). MEASUREMENTS: Outcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude). RESULTS: Depression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ2 = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = -0.40, 95% confidence interval (CI): -0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: -0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = -0.52, n = 15, p = 0.049). CONCLUSION: Confirmatory trials are needed, given the low age-specific sample sizes here, to determine if TranS -C's produces durable depression responses by increasing sleep-wake rhythm stability in older adults and improving insomnia symptoms in younger adults. BRIEF ARTICLE SUMMARY: The authors evaluated preliminary efficacy of a behavioral intervention that targets sleep/sleep-wake rhythms, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms in people with serious mental illness. TranS-C was associated with higher depression response rates than treatment as usual 6-months postintervention. The degree of depression symptom response 6-months later was related to the degree of treatment phase improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults). A pragmatic nonpharmacologic intervention, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction, has preliminary efficacy for improving sleep-wake factors and depression symptoms.

Risk for Complicated Grief After the COVID-19 Death of a Marital Partner in Late Life.

OBJECTIVE: To identify 1) complicated grief symptom clusters among acutely-bereaved older adults who have lost a spouse to COVID-19 and 2) if spousal death due to COVID-19 increased risk of developing probable PGD METHODS: Eighty adults participating in a randomized controlled trial for depression prevention (mean age [± SD] = 70.4 [6.6]) completed the Inventory of Complicated Grief, every 3 months over a maximum of 15 months. Twenty-four percent (n = 19) of participants lost a spouse to COVID-19; 76% (n = 61) lost a spouse to other causes of death. Adjusted linear regression examined the associations between COVID-19 bereavement and six symptom clusters: yearning and preoccupation, anger and bitterness, shock and disbelief, estrangement from others, hallucinations, and behavior change. RESULTS: Compared to the non-COVID-19 group, the COVID-19 bereaved group reported greater shock and disbelief, hallucinations of the deceased, and estrangement from others. COVID-19 death was also associated with higher risk for probable prolonged grief disorder (PGD) at 12 months (odds ratio = 4.38, p = 0.027). CONCLUSIONS: Older adults who have lost a spouse to COVID-19 present with specific symptoms of distress and may eventually require clinical care for PGD.

Initial evidence regarding the neurobiological basis of psychological symptoms in dementia caregivers.

Mood symptoms and disorders are common in dementia caregivers, who can be exposed to a myriad of potential stressors including their care recipient's neuropsychiatric symptoms. Existing evidence indicates that the effects of potentially stressful exposures on mental health depend on the caregiver's individual characteristics and responses. Specifically, prior studies indicate that risk factors measured on psychological (e.g., emotion-focused/behaviorally disengaged coping responses) and behavioral (e.g., sleep and activity restriction) levels of analysis may confer the effects of caregiving exposures on mental health. Theoretically, this process from caregiving stressors and other risk factors to mood symptoms is neurobiologically mediated. This article reviews recent studies that used brain imaging to identify neurobiological factors that are related to psychological outcomes in caregivers. Available observational data indicate that psychological outcomes in caregivers are related to differences in the structure/function of regions involved in socio-affective information processing (prefrontal), autobiographical memory (the posterior cingulate), and stress (amygdala). In addition, two small randomized controlled trials using repeated brain imaging showed that Mentalizing Imagery Therapy (a mindfulness program) increased prefrontal network connectivity and reduced mood symptoms. These studies raise the possibility that, in the future, brain imaging may be useful to detect the neurobiological basis of a given caregiver's mood vulnerability and guide the selection of interventions that are known to modify it. However, there remains a need for evidence on whether brain imaging improves on simpler/inexpensive measurement modalities like self-report for identifying vulnerable caregivers and matching them with efficacious interventions. In addition, to target interventions, more evidence is needed regarding the effects that both risk factors and interventions have on mood neurobiology (e.g., how persistent emotion-focused coping, sleep disruption, and mindfulness affect brain function).

Elusive hypersomnolence in seasonal affective disorder: actigraphic and self-reported sleep in and out of depressive episodes.

BACKGROUND: Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission. METHODS: Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities. RESULTS: In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05). CONCLUSION: Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.

Shared and distinct abnormalities in sleep-wake patterns and their relationship with the negative symptoms of Schizophrenia Spectrum Disorder patients.

Sleep and rest-activity-rhythm (RAR) abnormalities are commonly reported in schizophrenia spectrum disorder (SSD) patients. However, an in-depth characterization of sleep/RAR alterations in SSD, including patients in different treatment settings, and the relationship between these alterations and SSD clinical features (e.g., negative symptoms) is lacking. SSD (N = 137 altogether, N = 79 residential and N = 58 outpatients) and healthy control (HC) subjects (N = 113) were recruited for the DiAPAson project. Participants wore an ActiGraph for seven consecutive days to monitor habitual sleep-RAR patterns. Sleep/rest duration, activity (i.e., M10, calculated on the 10 most active hours), rhythm fragmentation within days (i.e., intra-daily variability, IV; beta, steepness of rest-active changes), and rhythm regularity across days (i.e., inter-daily stability, IS) were computed in each study participant. Negative symptoms were assessed in SSD patients with the Brief Negative Symptom Scale (BNSS). Both SSD groups showed lower M10 and longer sleep/rest duration vs. HC, while only residential patients had more fragmented and irregular rhythms than HC. Compared to outpatients, residential patients had lower M10 and higher beta, IV and IS. Furthermore, residential patients had worse BNSS scores relative to outpatients, and higher IS contributed to between-group differences in BNSS score severity. Altogether, residentials and outpatients SSD had both shared and unique abnormalities in Sleep/RAR measures vs. HC and relative to one another, which also contributed to the patients' negative symptom severity. Future work will help establish whether improving some of these measures may ameliorate the quality of life and clinical symptoms of SSD patients.

Actigraphic correlates of neuropsychiatric symptoms in adults with focal epilepsy.

OBJECTIVES: Disability in patients with epilepsy (PWEs) is multifactorial: beyond seizure frequency/severity, PWEs are prone to a range of neuropsychiatric, cognitive, and somatic comorbidities that significantly affect quality of life. Here, we explored how variations in seizure severity and the burden of self-reported somatic/neuropsychiatric symptoms correlate with disruptions to 24 h activity patterns (rest-activity rhythms [RARs]), determined through wrist accelerometry/actigraphy. METHODS: Multiday wrist-actigraphy recordings were obtained from 59 adult patients with focal epilepsy (44% male, ages 18-72), who contemporaneously responded to validated psychometric instruments to measure anxiety, depression, sleepiness, and somatic symptoms. We conducted a similar in silico psychometric-actigraphic correlation in a publicly available data set of 1747 Hispanic subjects (35% male, ages 18-65) from the Study of Latinos (SOL) Sueño Ancillary Study. RARs were analyzed via a sigmoidally-transformed cosine model (quantifying amplitude, steepness, acrophase, and robustness) and nonparametric measures to estimate RAR stability, fragmentation, and sleep. RESULTS: Compared with matched SOL subjects, RARs from PWE subjects featured a significantly lower amplitude, a wider rest phase, and significantly more total daily sleep. Within PWEs, similar RAR distortions were associated with seizure intractability and/or anticonvulsant polytherapy, whereas high anxiety, depression, and somatic symptom scores were associated with lower RAR robustness and acrophase delay. We applied the SOL data set to train logistic regression models to dichotomously classify subjective anxiety, depression, and sleepiness symptoms using demographic and RAR parameters. When tested on PWEs, these models predicted prevalent anxiety and depression symptom burden (accuracy ~70%) but failed to predict subjective sleepiness. SIGNIFICANCE: Together these results demonstrate that RAR features may encode prevalent depression and anxiety symptoms in patients with focal epilepsy, potentially offering wearable-derived endpoints to adjunct clinical care and drug/device trials. With larger PWE-specific actigraphic-psychometric data sets, we may identify RAR signatures that may more precisely correlate with varying seizure frequency, the burden of anticonvulsant therapy, and prevalent mood/anxiety symptoms.

Rest-Activity Rhythm Characteristics Associated With Depression Symptoms in Stroke Survivors.

OBJECTIVE: To examine which 24-hour rest-activity rhythm (RAR) characteristics are associated with depression symptoms in stroke survivors. DESIGN: Cross-sectional observational study examining associations of RAR characteristics with the presence of depression symptoms adjusting for age, sex, race, and medical comorbidity. SETTING: Community setting. PARTICIPANTS: Stroke survivors: (1) recruited locally (N women=35, N men=28) and (2) a nationally representative probability sample (the National Health and Nutrition Examination Survey [NHANES]; N women=156, N men=124). INTERVENTIONS: None. MEASUREMENTS: Objective RAR characteristics derived from accelerometer recordings including activity onset/offset times and non-parametric measures of RAR strength (relative amplitude), stability (interdaily stability), and fragmentation (intradaily variability). The presence of depression symptoms was categorized using Patient Health Questionnaire scores. RESULTS: In both samples, the only RAR characteristic associated with depression symptoms was intradaily variability (fragmentation): local sample, odds ratio=1.96 [95% confidence interval=1.05-3.63]; NHANES sample, odds ratio=1.34, [95% confidence interval=1.01-1.78]). In the NHANES sample, which included both mild and moderate/severe depression, the association between 24-hour sleep-wake fragmentation and depression symptoms was driven by moderate-to-severe cases. CONCLUSIONS: Stroke survivors with higher levels of RAR fragmentation were more likely to have depression symptoms in both samples. These findings have implications, given prior studies in general samples linking RAR fragmentation with future depression and dementia risk. Research is needed to establish the potential consequences, mechanisms, and modifiability of RAR fragmentation in stroke survivors.

A digital health intervention to stabilize the 24-hour rhythm of sleep, meals, and physical activity for reducing depression among older bereaved spouses: Protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence of depression and disruption to 24-h sleep-wake routines following the death of a spouse in late-life, no bereavement interventions have been developed to re-entrain a regular sleep-wake routine among older widow(er)s. We describe the rationale and methodology of the NIH-funded WELL Study (Widowed Elders' Lifestyle after Loss), a randomized controlled trial (RCT) comparing the efficacy of a digital health intervention (DHI) to enhanced usual care (EUC) arm for reducing depression symptoms in older spousally-bereaved adults. METHODS: We will randomize approximately 200 recently bereaved (<12 months) adults aged 60+ years to one of two 12-week interventions: digital monitoring of the timing and regularity of sleep, meals, and physical activity plus weekly motivational health coaching; or enhanced usual care consisting of weekly telephone calls and similar assessment schedules. Participants will complete self-report and clinical assessments at baseline, post-intervention, and 3-, 6-, and 12-months post-intervention, and objective actigraphic assessments of their 24-h rest-activity rhythm (RAR) at baseline and 1-, 2-, and 3-months during the intervention. The primary outcome is change in depression symptoms burden (using the Hamilton Rating Scale for Depression) from pre- to post-intervention and over 12 months of follow-up. DISCUSSION: WELL Study findings will inform the development of widely generalizable and scalable technology-based interventions to support bereaved spouses in community-based settings. Clinical http://Trials.gov Identifier: NCT04016896.

Activity patterns related to depression symptoms in stressed dementia caregivers.

OBJECTIVES: Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale-Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later. RESULTS: Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen's d ≤ -0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit ß = -0.8, 95% confidence interval: -1.6, -0.1, p = 0.03) independent of self-reported activity restriction and other key factors. CONCLUSIONS: These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).

Relationships between rest-activity rhythms, sleep, and clinical symptoms in individuals at clinical high risk for psychosis and healthy comparison subjects.

Sleep-wake disturbances in individuals at clinical high risk (CHR) of psychosis may relate to increased symptom severity and contribute to disease progression. Here, we examined differences in rest-activity rhythms (RAR) measures, derived from actigraphy, and objective sleep outcomes, derived from electroencephalography (EEG), between 12 CHR and 16 healthy comparison (HC) individuals. Further, we examined the relationships between RAR disturbances, objective sleep outcomes and clinical psychosis symptoms (i.e., negative, positive, disorganized, general symptoms). Sleep-wake behaviors were monitored via actigraphy for 3-7 days (CHR: 5.7 ± 1.7 days; HC: 6.3 ± 1.2 days) prior to participants spending a night in the sleep laboratory, which was monitored with EEG. Separate regressions were used to examine the effect of clinical group on RAR measures and objective sleep outcomes after controlling for age and gender. CHR participants were found to be less active, specifically during the evening (17:00-20:00; ß = 1.145, SE = 0.362, p = .004) and nighttime (21:00-24:00; ß = 1.152, SE = 0.326, p = .002) relative to HC. Further, CHR participants had more fragmented sleep (wake after sleep onset: ß = 0.888, SE = 0.395, p = .034) and more hyperarousal during sleep (NREM gamma activity: ß = 1.087, SE = 0.348, p = .005), but these sleep disturbances were not related to reduced activity or clinical symptoms, whereas lower nighttime activity was related to more disorganized symptoms (ρ = -.640, p = .025). Thus, increasing activity through behavioral interventions may have additional beneficial effects on CHR clinical symptoms.

Association of 24-Hour Activity Pattern Phenotypes With Depression Symptoms and Cognitive Performance in Aging.

Importance: Evidence regarding the nature and prevalence of 24-hour activity pattern phenotypes in older adults, especially those related to depression symptoms and cognition, is needed to guide the development of targeted mechanism research and behavioral interventions. Objectives: To identify subgroups of older adults with similar 24-hour activity rhythm characteristics and characterize associated depression symptoms and cognitive performance. Design, Setting, and Participants: From January to March 2022, a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination and Survey (NHANES) accelerometer study was conducted. The NHANES used a multistage probability sample that was designed to be representative of noninstitutionalized adults in the US. The main analysis included participants 65 years or older who had accelerometer and depression measures weighted to represent approximately 32 million older adults. Exposures: Latent profile analysis identified subgroups with similar 24-hour activity pattern characteristics as measured using extended-cosine and nonparametric methods. Main Outcomes and Measures: Covariate-adjusted sample-weighted regressions assessed associations of subgroup membership with (1) depression symptoms defined as 9-Item Patient Health Questionnaire (PHQ-9) scores of 10 or greater (PHQ-9) and (2) having at least psychometric mild cognitive impairment (p-MCI) defined as scoring less than 1 SD below the mean on a composite cognitive performance score. Results: The actual clustering sample size was 1800 (weighted: mean [SD] age, 72.9 [7.3] years; 57% female participants). Clustering identified 4 subgroups: (1) 677 earlier rising/robust (37.6%), (2) 587 shorter active period/less modelable (32.6%), (3) 177 shorter active period/very weak (9.8%), and (4) 359 later settling/very weak (20.0%). The prevalence of a PHQ-9 score of 10 or greater differed significantly across groups (cluster 1, 3.5%; cluster 2, 4.7%; cluster 3, 7.5%; cluster 4, 9.0%; χ2 P = .004). The prevalence of having at least p-MCI differed significantly across groups (cluster 1, 7.2%; cluster 2, 12.0%; cluster 3, 21.0%; cluster 4, 18.0%; χ2 P < .001). Five of 9 depression symptoms differed significantly across subgroups. Conclusions and Relevance: In this cross-sectional study, findings indicate that approximately 1 in 5 older adults in the US may be classified in a subgroup with weak activity patterns and later settling, and approximately 1 in 10 may be classified in a subgroup with weak patterns and shorter active duration. Future research is needed to investigate the biologic processes related to these behavioral phenotypes, including why earlier and robust activity patterns appear protective, and whether modifying disrupted patterns improves outcomes.

Associations of Modifiable Behavioral Risk Factor Combinations at 65 to 74 Years Old With Cognitive Health Span for 20 Years.

OBJECTIVE: Behavioral risk factors for dementia tend to co-occur and interrelate, especially poor diet, physical inactivity, sleep disturbances, and depression. Having multiple of these modifiable behavioral risk factors (MBRFs) may predict a particularly shortened cognitive health span and therefore may signal high-risk status/high intervention need. METHODS: These secondary analyses of data from the Cardiovascular Health Study included 3149 participants aged 65 to 74 years (mean [standard deviation {SD}] age = 69.5 [2.5] years; 59.6% female). MBRF exposures were self-reports regarding a) diet, b) activity, c) sleep, and d) depression symptoms. We primarily analyzed MBRF counts. For up to 26 years of follow-up, we assessed the a) number of remaining cognitively healthy life-years (CHLYs) and b) percentage of remaining life-years (LYs) that were CHLYs (%CHLY). We estimated CHLYs as time before a dementia diagnosis, cognitive screener scores indicating impairment, proxy report indicating significant cognitive decline, or dementia medication use. RESULTS: Participants averaged a remaining 16 LYs (SD = 7 LYs), 12.2 CHLYs (SD = 6.6 CHLYs), and 78.1% of LYs being CHLYs (SD = 25.6 CHLYs). Compared with having no MBRFs, having one was associated with ~1 less LY and CHLY, but not a relatively lower %CHLY. In contrast, having 3+ MBRFs was associated with about 2 to 3 fewer LYs and CHLYs as well as about 6% lower %CHLY (95% confidence interval = -9.0 to -2.5 %CHLYs; p = .001). CONCLUSIONS: MBRF-related reductions in the cognitive health span are most apparent when people have multiple MBRFs. Future research is needed to determine if/how behavioral risks converge mechanistically and if dementia prevention efficacy improves when targeting MBRF combinations.

Actigraphy-derived sleep health profiles and mortality in older men and women.

STUDY OBJECTIVES: To identify actigraphy sleep health profiles in older men (Osteoporotic Fractures in Men Study; N = 2640) and women (Study of Osteoporotic Fractures; N = 2430), and to determine whether profile predicts mortality. METHODS: We applied a novel and flexible clustering approach (Multiple Coalesced Generalized Hyperbolic mixture modeling) to identify sleep health profiles based on actigraphy midpoint timing, midpoint variability, sleep interval length, maintenance, and napping/inactivity. Adjusted Cox models were used to determine whether profile predicts time to all-cause mortality. RESULTS: We identified similar profiles in men and women: High Sleep Propensity [HSP] (20% of women; 39% of men; high napping and high maintenance); Adequate Sleep [AS] (74% of women; 31% of men; typical actigraphy levels); and Inadequate Sleep [IS] (6% of women; 30% of men; low maintenance and late/variable midpoint). In women, IS was associated with increased mortality risk (Hazard Ratio [HR] = 1.59 for IS vs. AS; 1.75 for IS vs. HSP). In men, AS and IS were associated with increased mortality risk (1.19 for IS vs. HSP; 1.22 for AS vs. HSP). CONCLUSIONS: These findings suggest several considerations for sleep-related interventions in older adults. Low maintenance with late/variable midpoint is associated with increased mortality risk and may constitute a specific target for sleep health interventions. High napping/inactivity co-occurs with high sleep maintenance in some older adults. Although high napping/inactivity is typically considered a risk factor for deleterious health outcomes, our findings suggest that it may not increase risk when it occurs in combination with high sleep maintenance.