Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Background Chronic insomnia is a common health problem with substantial consequences in older adults. Cognitive behavioral treatments are efficacious but not widely available. The aim of this study was to test the efficacy of brief behavioral treatment for insomnia (BBTI) vs an information control (IC) condition. Methods A total of 79 older adults (mean age, 71.7 years; 54 women [70%]) with chronic insomnia and common comorbidities were recruited from the community and 1 primary care clinic. Participants were randomly assigned to either BBTI, consisting of individualized behavioral instructions delivered in 2 intervention sessions and 2 telephone calls, or IC, consisting of printed educational material. Both interventions were delivered by a nurse clinician. The primary outcome was categorically defined treatment response at 4 weeks, based on sleep questionnaires and diaries. Secondary outcomes included self-report symptom and health measures, sleep diaries, actigraphy, and polysomnography. Results Categorically defined response (67% [n=26] vs 25% [n=10]; χ2=13.8) (P<.001) and the proportion of participants without insomnia (55% [n=21] vs 13% [n=5]; χ2=15.5) (P<.001) were significantly higher for BBTI than for IC. The number needed to treat was 2.4 for each outcome. No differential effects were found for subgroups according to hypnotic or antidepressant use, sleep apnea, or recruitment source. The BBTI produced significantly better outcomes in self-reported sleep and health (group × time interaction, F5,73=5.99, P<.001), sleep diary (F8,70= 4.32, P<.001), and actigraphy (F4,74=17.72, P<.001), but not polysomnography. Improvements were maintained at 6months. Conclusion We found that BBTI is a simple, efficacious, and durable intervention for chronic insomnia in older adults that has potential for dissemination across medical settings.

Older adults with specific EEG sleep characteristics have an excess risk of dying beyond that associated with age, gender, or medical burden. The findings suggest that interventions to optimize and protect older adults' sleep initiation, continuity, and quality may be warranted.

Summary Background Treatment-resistant major depressive disorder is common and potentially life-threatening in older persons, in whom little is known about the benefits and risks of augmentation pharmacotherapy. Methods We conducted a multi-site, placebo-controlled, randomized clinical trial to test the efficacy and safety of aripiprazole augmentation for older adults with treatment-resistant depression. We treated 468 participants aged 60 and older with current major depressive episode with venlafaxine extended-release (ER); 96 (20.5%) did not complete this open phase, 191 (40.8%) remitted, and 181 (38.7%) did not remit and were randomized to 12 weeks of double-blind augmentation with aripiprazole or placebo. The computer-generated randomization was done in blocks and stratified by site. The primary endpoint was remission, defined as Montgomery-Asberg Depression Rating Scale scores ≤10 (and at least two points below the score at the start of the randomized phase) at both of the final two consecutive visits. We also assessed resolution of suicidal ideation, and safety and tolerability with cardiometabolic and neurological measures. Analyses were conducted according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT00892047. Findings Older adults on aripiprazole had a higher remission rate than those on placebo (44% versus 29%; odds ratio [OR]=2.0, 95% CI 1.1–3.7, p=0.03; number needed to treat [NNT]=6.6 [95% CI 3.5–81.8]). Overall, remission was stable during 12 additional weeks of continuation treatment. The resolution of suicidal ideation was more marked with aripiprazole than with placebo. Akathisia was the most common adverse effect (27% of participants on aripiprazole). Compared to placebo, aripiprazole was also associated with more Parkinsonism but not with treatment-emergent suicidal ideation, QTc prolongation, or increases in adiposity, glucose, insulin, or lipids. Interpretation In older adults who fail to achieve remission from depression with a first-line antidepressant, the addition of aripiprazole is effective in achieving and sustaining remission. Tolerability concerns include potential for akathisia and Parkinsonism. Funding National Institute of Mental Health, UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, National Center for Advancing Translational Sciences, and the Campbell Family Mental Health Research Institute.

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Objective Pharmacological and cognitive-behavioral treatments targeting insomnia and nightmares have been shown to be effective in the treatment of military veterans with sleep complaints comorbid with symptoms of stress-related disorders, including Post-Traumatic Stress Disorder (PTSD), but the two approaches have not been directly compared. This randomized controlled trial compared the effects of prazosin vs. a behavioral sleep intervention (BSI), targeting nightmares and insomnia against a placebo pill control condition on sleep and daytime symptoms. Methods Fifty United States military veterans (mean age 40.9 years, SD = 13.2 years) with chronic sleep disturbances were randomized to prazosin (n = 18), BSI (n = 17), or placebo (n = 15). Each intervention lasted eight weeks. Participants completed self-report measures of insomnia severity, sleep quality, and sleep disturbances. All kept a sleep diary throughout the intervention period. Polysomnographic studies were conducted pre- and post-intervention. Results Both active treatment groups showed greater reductions in insomnia severity and daytime PTSD symptom severity. Sleep improvements were found in 61.9% of those who completed the active treatments and 25% of those randomized to placebo. Conclusion BSI and prazosin were both associated with significant sleep improvements and reductions in daytime PTSD symptoms in this sample of military veterans. Sleep-focused treatments may enhance the benefits of first-line PTSD treatments.

SUMMARYThis study explored the relationship between circadian performance rhythms and rhythms in rectal temperature, plasma cortisol, plasma melatonin, subjective alertness and well-being. Seventeen healthy young adults were studied under 36 h of 'unmasking' conditions (constant wakeful bedrest, temporal isolation, homogenized 'meals') during which rectal temperatures were measured every minute, and plasma cortisol and plasma melatonin measured every 20 min. Hourly subjective ratings of global vigour (alertness) and affect (well-being) were obtained followed by one of two performance batteries. On odd-numbered hours performance (speed and accuracy) of serial search, verbal reasoning and manual dexterity tasks was assessed. On even-numbered hours, performance (% hits, response speed) was measured at a 25-30 min visual vigilance task. Performance of all tasks (except search accuracy) showed a significant time of day variation usually with a nocturnal trough close to the trough in rectal temperature. Performance rhythms appeared not to reliably differ with working memory load. Within subjects, predominantly positive correlations emerged between good performance and higher temperatures and better subjective alertness; predominantly negative correlations between good performance and higher plasma levels of cortisol and melatonin. Temperature and cortisol rhythms correlated with slightly more performance measures (5/7) than did melatonin rhythms (4/7). Global vigour correlated about as well with performance (5/7) as did temperature, and considerably better than global affect (1/7). In conclusion: (1) between-task heterogeneity in circadian performance rhythms appeared to be absent when the sleep/wake cycle was suspended; (2) temperature (positively), cortisol and melatonin (negatively) appeared equally good as circadian correlates of performance, and (3) subjective alertness correlated with performance rhythms as well as (but not better than) body temperature, suggesting that performance rhythms were not directly mediated by rhythms in subjective alertness.

SummaryAge-associated alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning may make individuals more susceptible to HPA dysregulation in the context of mood and anxiety disorders. Little to no research has been done to examine HPA axis function in generalized anxiety disorder (GAD), particularly in late-life GAD, the most prevalent anxiety disorder in the elderly. The study sample consisted of 71 GAD subjects and 40 nonanxious comparison subjects over 60 years of age. We examined the hypotheses that elderly individuals with GAD will have elevated salivary cortisol levels compared to nonanxious subjects, and that elevated cortisol levels in GAD will be associated with measures of symptom severity. We report that late-life GAD is characterized by elevated basal salivary cortisol levels, with higher peak cortisol levels and larger areas under the curve, compared to nonanxious subjects. Additionally, severity of GAD as measured by the GAD Severity Scale and the Penn State Worry Questionnaire are positively correlated with cortisol levels. These data demonstrate HPA axis dysfunction in late-life GAD and suggest the need for additional research on the influence of aging on HPA axis function in mood and anxiety disorders.