Summary No systematic review of epidemiological evidence has examined risk factors for sleep disturbances among older adults. We searched the PUBMED database combining search terms targeting the following domains (1) prospective, (2) sleep, and (3) aging, and identified 21 relevant population-based studies with prospective sleep outcome data. Only two studies utilized objective measures of sleep disturbance, while six used the Pittsburgh Sleep Quality Index (PSQI) and thirteen used insomnia symptoms or other sleep complaints as the outcome measure. Female gender, depressed mood, and physical illness were most consistently identified as risks for future sleep disturbances. Less robust evidence implicated the following as potentially relevant predictors: lower physical activity levels, African-American race, lower economic status, previous manual occupation, widowhood, marital quality, loneliness and perceived stress, preclinical dementia, long-term benzodiazepine and sedative use, low testosterone levels, and inflammatory markers. Chronological age was not identified as a consistent, independent predictor of future sleep disturbances. In conclusion, prospective studies have identified female gender, depressed mood, and physical illness as general risk factors for future sleep disturbances in later life, although specific physiological pathways have not yet been established. Research is needed to determine the precise mechanisms through which these factors influence sleep over time.

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Inflammatory markers, lifestyle, and health status explained mortality risk associated with short sleep, while the mortality risk associated with long sleep was explained predominantly by lifestyle and health status.

Objectives To evaluate whether objectively-measured sleep characteristics are associated with mortality risk independent of inflammatory burden and comorbidity. Methods The MrOS Sleep Study (conducted in 2003-2005) included community-dwelling older men (n=2531; average age of 76.3 (5.5 s.d.)). Sleep measures from in-home polysomnography and wrist actigraphy and assessments of serum inflammatory markers levels (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), tumor necrosis factor-α soluble receptor II (sTNF-RII) and interferon–γ (IFN-γ)) were obtained. Vital status was ascertained over an average follow-up of 7.4 (1.9 s.d.) years. Results Three of the seven main sleep measures examined were independently associated with greater inflammatory burden. Mortality risk associated with prolonged (≥10% total sleep time) blood oxygen desaturation and short (<5 hours) sleep duration was attenuated to non-significance after adjusting for inflammatory burden or medical burden/lifestyle factors. Severe blood oxygen desaturation (adjusted hazard ratio (aHR)=1.57, 95% confidence interval (CI): 1.11-2.22), sleep fragmentation (aHR=1.32, 95% CI: 1.12-1.57), and a lower percentage of sleep in rapid eye movement (REM; aHR per s.d.=0.90, 95% CI: 0.93-0.97) were independently associated with mortality. Conclusions Short sleep duration and prolonged blood oxygen desaturation were independently associated with inflammatory burden, which attenuated associations between these sleep characteristics and mortality. Medical and lifestyle factors also substantially attenuated most sleep-mortality associations, suggesting complex relations between sleep, inflammation, and disease. Sleep fragmentation, severe blood oxygen desaturation, and the percentage of sleep time in REM were independently related to mortality risk. Future studies with repeated measures of mediators/confounds will be necessary to achieve a mechanistic understanding of sleep-related mortality risk.

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. We investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). We found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. This study offers new data, indicating that functional connectivity changes differ depending on treatment response and can occur shortly after exposure to antidepressant medication.

IMPORTANCE More than 50% of older adults with late-life major depressive disorder fail to respond to initial treatment with first-line pharmacological therapy. OBJECTIVES To assess typical patterns of response to an open-label trial of extended-release venlafaxine hydrochloride (venlafaxine XR) for late-life depression and to evaluate which clinical factors are associated with the identified longitudinal response patterns. DESIGN, SETTING, AND PARTICIPANTS Group-based trajectory modeling was applied to data from a 12-week open-label pharmacological trial conducted in specialty care as part of the Incomplete Response in Late Life: Getting to Remission Study. Clinical prognostic factors, including domain-specific cognitive performance and individual depression symptoms, were examined in relation to response trajectories. Participants included 453 adults aged 60 years or older with current major depressive disorder. The study was conducted between August 2009 and August 2014. INTERVENTION Open-label venlafaxine XR (titrated up to 300 mg/d) for 12 weeks.MAIN OUTCOMES AND MEASURES Subgroups exhibiting similar response patterns were derived from repeated measures of overall depression severity obtained using the Montgomery-Asberg Depression Rating Scale.RESULTS Among the 453 study participants, 3 subgroups with differing baseline depression severity clearly responded to treatment: one group with the lowest baseline severity had a rapid response (n = 69 [15.23%]), and distinct responses were also apparent among groups starting at moderate (n = 108 [23.84%]) and higher (n = 25 [5.52%]) baseline symptom levels. Three subgroups had nonresponding trajectories: 2 with high baseline symptom levels (totaling 35.98%: high, nonresponse 1, n = 110 [24.28%]; high, nonresponse 2, n = 53 [11.70%]) and 1 with moderate baseline symptom levels (n = 88 [19.43%]). Several factors were independently associated with having a nonresponsive trajectory, including greater baseline depression severity, longer episode duration, less subjective sleep loss, more guilt, and more work/activity impairment (P < .05). Higher delayed memory (list recognition) performance was independently associated with having a rapid response (adjusted odds ratio = 2.22; 95% CI, 1.18-4.20). CONCLUSIONS AND RELEVANCEBased on the observed trajectory patterns, patients who have late-life depression with high baseline depression severity are unlikely to respond after 12 weeks of treatment with venlafaxine XR. However, high baseline depression severity alone may be neither a necessary nor sufficient predictor of treatment nonresponse.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00892047

An aggregate, multidimensional measure of sleep health was associated with both prevalent and incident clinically-significant depression symptoms in a gradient fashion. Future studies are warranted to extend these findings in different populations and with different health outcomes.

Activity rhythms disturbances and depression often co-occur among older adults. However, little is known about how activity rhythm disturbances themselves co-occur, or how disturbances to multiple aspects of the activity rhythm relate to depression over time. In the current study, we performed a Latent Class Analysis to derive sub-groups of older men (total n=2933, mean age=76.28, SD=5.48) who shared similar patterns of activity rhythm disturbances (defined as extreme values of modeled activity rhythm parameters). We found eight sub-groups with distinct combinations of activity rhythm disturbances: one had all normative activity rhythm parameters (32.09%), one had only lower activity (10.06%), three had earlier activity (totaling 26.96%), and three had later activity (totaling 30.89%). Groups with similar timing were distinguished depending on whether the relative length of the active period was shorter and/or if the activity rhythm had lesser amplitude/robustness. We next examined whether the derived activity rhythm sub-groups were associated with different rates of change in depression symptom levels over an average of 5.5 (0.52 SD) follow-up years. The sub-group with lower activity only had faster increases in depressive symptoms over time (compared to the group with normative rhythm parameters), but this association was accounted for by adjustments for concurrently assessed health status covariates. Independent of these covariates, we found four activity rhythm disturbance sub-groups that experienced faster depressive symptom increases (compared with the normative sub-group): These included all three sub-groups that had later activity timing, and one sub-group that had earlier activity timing plus a shorter active period and a dampened rhythm. Low activity rhythm height/robustness with normal timing therefore may mark depression risk that is attributable to co-occurring disease processes; in contrast, having late or combined early/compressed/dampened activity rhythms may independently contribute to depression symptom development. Our findings suggest that activity rhythm related depression risk is heterogeneous, and may be detected when multiple aspects of rhythm timing are delayed or when early timing is accompanied by compressed/dampened activity rhythms. Future studies should consider how distinct combinations of altered activity rhythm timing and height/robustness develop and conjointly determine health risks. Future research is also needed to determine whether/how activity rhythms can be modified to improve depression outcomes.