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.

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.

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.

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.

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.

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).

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.

Adaptation and Pilot Study of a Behavioral Intervention Targeting Morning Activation Deficits in Dementia Caregivers: Scheduling Activity and Monitoring Mornings (SAMM).

OBJECTIVES: Morning activation deficits (MADs) correlate with depression symptom persistence in older dementia caregivers. To clarify the potential of MADs as a target for depression interventions, we aimed to: 1) adapt an existing behavioral activation program, Engage therapy, to target mornings; and 2) evaluate effects on self-reported MADs and depression symptoms. METHODS: While trialing the 9-week Engage adaption (targeting mornings) in six older dementia caregivers, we incorporated feedback and finalized an adapted program called Scheduling Activity and Monitoring Mornings (SAMM). We delivered the SAMM protocol to 13 dementia caregivers (all female; mean age = 69, standard deviation = 7). We report modifications made/rationale, as well as changes in subjective MADs (relevant items from the Composite Scale of Morningness) and depression symptoms (Patient Health Questionnaire - 9). RESULTS: Using caregiver and expert input, we adapted the protocol to: include educational materials/content describing the potential relationship between morning inactivity and depression; target activity scheduling within 2 hours of awakening (preferably earlier); and focus only on the main components of morning activity scheduling, planning, and monitoring. This program was associated with decreases in subjective MADs averaging 29% at week 4, 52% at week 6, and 57% by week 9 (all p's <0.005). Initial depression symptoms were significantly reduced, by 62%, at week 9. CONCLUSIONS: These preliminary findings suggest that subjective MADs can be modified pragmatically, and that doing so may have antidepressant effects. A controlled trial with measures of the putative mechanism is needed to clarify whether, and if so how, targeting MAD with SAMM causally perturbs depression's mechanisms.

Spectral sleep electroencephalographic correlates of sleep efficiency, and discrepancies between actigraphy and self-reported measures, in older men.

Discrepancies between actigraphic and self-reported sleep measures are common. Studies of people with insomnia, in whom both sleep disturbances and discrepancy are common, suggest disturbances and discrepancy reflect differences in the sleeping brain's activity measurable using spectral electroencephalogram (EEG). Disentangling effects of discrepancy and disturbance on sleep EEG could help target research on the consequences and treatments of different sleep phenotypes. We therefore categorized participants in a cohort study including 2,850 men (average age = 76 years, standard deviation = 5.5) into four groups using median splits on actigraphic and self-reported sleep efficiency (SE). We compared spectral power between these groups in 1-Hz bins up to 24 Hz. Compared with the concordant-high SE group: (a) the group with high actigraphic and low self-reported SE had higher spectral power from 11-15 Hz across the night; (b) both groups with low actigraphic SE had higher power across the 15-24 Hz range, predominantly in early cycles, and greater slow frequency power in later cycles. These findings suggest that perceived wakefulness undetected by actigraphy may result from or drive activity corresponding to spindles. We also found, consistent with hyperarousal models, that low SE detectable via actigraphy was related to higher frequency power in the beta range; actigraph-measured inefficiency was also associated with later slow oscillations, potentially representing attempts to dissipate homeostatic drive elevated from earlier hyperarousal. These distinct spectral EEG markers (of low SE measured with actigraphy vs. low perceived SE that is not captured by actigraphy) may have different causes or consequences.

Subjective Sleep Quality and Trajectories of Interleukin-6 in Older Adults.

BACKGROUND: We aimed to identify trajectories of inflammation in older adults at elevated risk for syndromal depression and anxiety and to determine whether baseline physical, cognitive, and psychosocial factors could distinguish 15-month longitudinal trajectories. METHODS: Older adults (N = 195, mean age (±SD) = 74.4 years (9.0) participating in three depression and anxiety prevention protocols completed a comprehensive battery of psychosocial assessments and provided blood samples for analysis of interleukin-6 (IL-6) every 3 months over a maximum of 15 months. Group-based trajectory modeling identified trajectories. Adjusted logistic regression examined associations between baseline factors and trajectory groups. RESULTS: Two 15-month trajectories were identified: stable lower IL-6 levels (84%; mean (±SD) = 3.2 (2.1) pg/mL); and consistently higher IL-6 levels (16%; mean = 9.5 (7.4) pg/mL). Poor sleep quality predicted consistently higher levels of IL-6 (OR = 1.9, 95% CI = 1.03-3.55). CONCLUSION: Poor sleep quality may represent a therapeutic target to reduce inflammation.

Cancer Bereavement and Depression Symptoms in Older Spouses: The Possible Modifying Role of the Circadian Rest-Activity Rhythm.

OBJECTIVES: This study examines the associations of cancer death and aspects of the 24-h circadian rest-activity rhythm (RAR) on depression symptoms in older spouses. METHODS: Participants included 46 adults aged 60-94 years (M = 73 years) who experienced the death of a spouse. We tested a multivariate model using cancer death (vs. non-cancer death) and RAR variables as correlates of depression symptoms while controlling for age, sex, physical illness burden, and preparedness for death. We also present a case example to describe the behavioral activity patterns of a participant bereaved by cancer. RESULTS: Cancer death was associated with elevated levels of depression symptoms. However, the timing of the RAR moderated this association. Cancer bereavement was associated with depression symptoms when participants "settled-down" after 11:00 PM. The case example illustrates how intrusive thoughts about death quality impacts a widower's drive to stay busy with daily activities. CONCLUSIONS: Settling down earlier in the evening is important for older spouses bereaved by cancer, in terms of fewer symptoms of depression. CLINICAL IMPLICATIONS: Objectively specifying the activity patterns of older spouses bereaved by cancer is a promising avenue for interventions that aim to reduce depression symptoms.

Trajectories of daytime sleepiness and their associations with dementia incidence.

Several studies have associated daytime sleepiness with risk of dementia, but it is unknown whether longstanding and emerging daytime sleepiness equally signal a risk of dementia, and whether other health factors explain these associations. In a prospective, population-based epidemiologic study, we (i) assessed associations of daytime sleepiness trajectories over 10 years with dementia incidence and (ii) examined whether selected health characteristics attenuated these associations. Using latent group-based trajectory analysis we categorized participants into three groups: (i) no daytime sleepiness (n = 959, 49.2%), (ii) emerging daytime sleepiness (n = 342, 17.5%) and (iii) persistent daytime sleepiness (n = 650, 33.3%). Compared with no daytime sleepiness, emerging and persistent daytime sleepiness were similarly associated with greater incident dementia risk (respective hazard ratios [95% confidence intervals] were 2.2 [1.3, 3.5] and 1.9 [1.2, 3.1]). Baseline blood pressure, body mass index, chronic disease diagnoses and symptoms of depression did not attenuate these associations. In contrast, lack of independence in instrumental activities of daily living attenuated the daytime sleepiness-dementia association by approximately 17%-21%. These findings suggest that persistent and emerging daytime sleepiness may signal a risk of dementia. However, the underlying mechanisms remain unclear. Further studies should investigate whether and how pathways to sleepiness, functional impairment and dementia pathophysiology interrelate and manifest together over time.

Regional Gray Matter Volume Links Rest-Activity Rhythm Fragmentation With Past Cognitive Decline.

OBJECTIVES: We examined the extent to which measures of neurodegeneration and cerebrovascular disease explain the rest-activity rhythm (RAR)-cognition link. METHODS: Seventy participants (mean age at MRI = 86, standard deviation (SD) = 2.6; 53% female) had cognitive, MRI, and accelerometer data. The slope of cognitive decline was defined applying a mixed model to 10 repeated Modified Mini Mental Status Test (3MS) measures over 14 years. Regional gray matter volume (GMV), white matter hyperintensities, and RARs were measured around year 12. RESULTS: Past 3MS decline was related to RAR fragmentation (per SD ß = -0.43, 95% confidence interval: -0.73, -0.14) and lower posterior parietal GMV (per standard deviation ß = 0.47, 95% confidence interval: 0.14, 0.79). Higher RAR fragmentation was related to lower posterior parietal GMV (Pearson r = -0.39, n = 70, p = 0.0007), which attenuated the association of RAR fragmentation and past cognitive decline by 17%. CONCLUSIONS: Longitudinal studies are warranted to understand the temporal relations and mechanisms linking RAR fragmentation and neurodegeneration.

Digital Monitoring of Sleep, Meals, and Physical Activity for Reducing Depression in Older Spousally-Bereaved Adults: A Pilot Randomized Controlled Trial.

OBJECTIVES: To evaluate the feasibility and acceptability of a behavioral intervention and explore its impact on depression symptom burden among older spousally-bereaved adults. METHODS: Participants were age ≥60 years, bereaved ≤8 months, and at high risk for depression. Participants were randomized to 12 weeks of digital monitoring of sleep, meals, and physical activity; digital monitoring plus health coaching; or enhanced usual care and followed for 9 months for new-episode depression. RESULTS: We enrolled 57 participants, 85% of eligible adults and 38% of all adults screened. We observed high levels of adherence in both digital monitoring (90%) and health coaching (92%); 88% of participants were retained. In linear mixed-effects models, depression symptoms significantly decreased, but the interaction between time and intervention was not significant. CONCLUSION: A behavioral intervention that uses both digital monitoring and motivational health coaching is feasible and acceptable to older bereaved adults.

White Matter Integrity Underlying Depressive Symptoms in Dementia Caregivers.

OBJECTIVE: We sought to determine whether the aspects of white matter connectivity implicated in major depression also relate to mild depressive symptoms in family dementia caregivers (dCGs). METHODS: Forty-one dCGs (average age=69 years, standard deviation=6.4) underwent a 7 Tesla 64-direction (12-minute) diffusion-weighted imaging sequence. We compared the fractional anisotropy (FA) of 11 white matter features between dCGs with (n=20) and without (n=21) depressive symptoms (Patient Health Questionnaire-9 scores ≥5). RESULTS: Caregivers reporting depression symptoms had lower FA in tracts connecting to the posterior cingulate cortex (Cohen's d = -0.9) and connecting dorsolateral prefrontal with rostral cingulate regions (Cohen's d = -1.2). CONCLUSIONS: Posterior cingulate and dorsolateral prefrontal-to-rostral cingulate white matter, implicated in prior studies of major depression, appear relevant to mild depression in dCGs.

Moderators of Response to Cognitive Behavior Therapy for Major Depression in Patients With Heart Failure.

OBJECTIVE: Although cognitive behavior therapy (CBT) is efficacious for major depression in patients with heart failure (HF), approximately half of patients do not remit after CBT. To identify treatment moderators that may help guide treatment allocation strategies and serve as new treatment targets, we performed a secondary analysis of a randomized clinical trial. Based on evidence of their prognostic relevance, we evaluated whether clinical and activity characteristics moderate the effects of CBT. METHODS: Participants were randomized to enhanced usual care (UC) alone or CBT plus enhanced UC. The single-blinded outcomes were 6-month changes in Beck Depression Inventory total scores and remission (defined as a Beck Depression Inventory ≤ 9). Actigraphy was used to assess daily physical activity patterns. We performed analyses to identify the specific activity and clinical moderators of the effects of CBT in 94 adults (mean age = 58, 49% female) with HF and major depressive disorder. RESULTS: Patients benefited more from CBT (versus UC) if they had the following: more medically severe HF (i.e., a higher New York Heart Association class or a lower left ventricular ejection fraction), more stable activity patterns, wider active periods, and later evening settling times. These individual moderator effects were small (|r| = 0.10-0.21), but combining the moderators yielded a medium moderator effect size (r = 0.38; 95% CI = 0.20-0.52). CONCLUSIONS: These findings suggest that increasing the cross-daily stability of activity patterns, and prolonging the daily active period, might help increase the efficacy of CBT. Given moderating effects of HF severity measures, research is also needed to clarify and address factors in patients with less severe HF that diminish the efficacy of CBT. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01028625.

Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults.

OBJECTIVES: Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. METHODS: In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]). RESULTS: All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r = -0.81, p = 0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction. CONCLUSIONS: Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging.

Determinants of Change in Objectively Assessed Sleep Duration Among Older Men.

We examined potential risk factors for changes in objectively assessed sleep duration within a large sample of community-dwelling older men. Participants (n = 1,055; mean baseline age = 74.6 (standard deviation (SD), 4.7) years) had repeated ActiGraph assessments (ActiGraph LLC, Pensacola, Florida) taken at the baseline (2003-2005) and follow-up (2009-2012) waves of the Outcomes of Sleep Disorders in Older Men Study (an ancillary study to the Osteoporotic Fractures in Men (MrOS) Study conducted in 6 US communities). Among men with a baseline nighttime sleep duration of 5-8 hours, we assessed the odds of becoming a short-duration (<5 hours) or long-duration (>8 hours) sleeper at follow-up. The odds of becoming a short-duration sleeper were higher among men with peripheral vascular disease (adjusted odds ratio (aOR) = 6.54, 95% confidence interval (CI): 2.30, 18.55) and ≥1 impairment in Instrumental Activities of Daily Living (IADL) (aOR = 2.57, 95% CI: 0.97, 6.78). The odds of becoming a long-duration sleeper were higher among those with greater baseline age (per SD increment, aOR = 1.49, 95% CI: 1.12, 2.00), depression symptoms (aOR = 3.13, 95% CI: 1.05, 9.36), and worse global cognitive performance (per SD increment of Modified Mini-Mental State Examination score, aOR = 0.74, 95% CI: 0.58, 0.94). Peripheral vascular disease and IADL impairment, but not chronological age, may be involved in the etiology of short sleep duration in older men. The risk factors for long-duration sleep suggest that deteriorating brain health predicts elongated sleep duration in older men.