Background

The pathophysiology of late-life depression (LLD) is complex and heterogeneous, with age-related processes implicated in its pathogenesis. This study examined the cross-sectional and longitudinal association between depressive symptoms and a baseline multibiomarker algorithm of biological age (BA) that aggregates indicators of inflammatory, metabolic, cardiovascular, lung, liver, and kidney functioning.

Method

Data were analyzed from 2,776 men and women from the prospective observational Health Aging and Body Composition Study, who had both evaluable chronological age (CA) and BA. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale.

Results

A covariate-adjusted regression model showed that BA (B = 0.03, p = .0471) but not CA (B = -0.01, p = .7185) is associated with baseline CES-D scores. The mean baseline BA for individuals with a CES-D ≥ 10 was 1.28 years greater than in those with a CES-D < 10. Comparatively, there is only a 0.05-year difference in mean CA between the two depression groups. A covariate-adjusted longitudinal model found that baseline BA predicts CES-D score at follow-up (B = 0.04, p = .0058), whereas CA does not (B = 0.03, p = .4125). Additionally, an older BA significantly predicted a CES-D ≥ 10 (B = 0.02, p = .032) over a 10-year period.

Conclusions

A multibiomarker index of an older adult's BA outperformed their CA in predicting subsequent increased and clinically significant depressive symptoms. This result supports the evolving view of LLD as a brain disorder resulting from deleterious age-associated changes across numerous physiological systems.

Objectives

Clinical trials can benefit from patient perspectives to inform trial design, such as choice of outcome measures. We engaged older adults in focus groups and surveys to get their perspective regarding needs in clinical research. The goal was to inform the development of a new clinical trial of medication strategies for treatment-resistant depression in older adults.

Methods

Older adults with depression participated in focus groups and a subsequent survey in St. Louis and New York. They were queried regarding research design features including outcomes, clinical management, mobile technology and iPad-administered assessments, the collection of DNA, and the receipt of their personal results.

Results

Patients told us: (1) psychological well-being and symptomatic remission are outcomes that matter to them; (2) it is important to measure not only benefits but risks (such as risk of falling) of medications; (3) for pragmatic trials in clinical settings, the research team should provide support to clinicians to ensure that medications are properly prescribed; (4) technology-based assessments are acceptable but there were concerns about data security and burden; (5) DNA testing is very important if it could improve precision care; (6) participants want to receive aggregate findings and their own personal results at the end of the study.

Conclusions

Patients gave useful and wide-ranging guidance regarding clinical and comparative effectiveness research in older adults. We discuss these findings with the goal of making the next generation of geriatric studies more impactful and patient-centered.

Objective

Treatment history can inform clinical decisions about subsequent treatment choices. The authors examined the impact of prior antidepressant treatment on treatment outcomes with venlafaxine only and then with augmentation with aripiprazole or placebo in depressed older adults.

Methods

The authors analyzed outcome data from a randomized, placebo-controlled clinical trial of aripiprazole augmentation in depressed older adults. The study consisted of an open-label lead-in phase with venlafaxine XR, followed by a placebo-controlled phase of aripiprazole augmentation. Treatment history was assessed with the Antidepressant Treatment History Form.

Results

Documented prior treatment failure predicted a reduced remission rate with venlafaxine. However, aripiprazole augmentation was efficacious in those with prior treatment failure (42.6% remission with aripiprazole versus 25.8% with placebo; χ(2) = 3.87 df = 1, p = 0.049).

Conclusion

Aripiprazole augmentation is an efficacious strategy in older depressed adults who fail to remit with two or more adequate antidepressant trials, including a course of venlafaxine.

Depression in later life is a severe public health problem, associated with higher rates of mortality, suicide, and dementia. Effectiveness of treatment is limited by the failure to deconstruct the heterogeneity of the illness and because diagnostic criteria, pathophysiological models, and treatment algorithms for depression are primarily based on studies of younger adults even though symptoms of the illness and physiology of the patient change with age. Thus, understanding how aging interacts with depressive illness may elucidate endophenotypes of late-life depression with different clinical manifestations and underlying mechanisms that can then be targeted with more personalized approaches to treatment. This paper proposes a model for the critical confluence between depression and frailty, a high-risk morbidity and mortality syndrome of later life. This model hypothesizes that characteristics of frailty in adults with late life depression represent the clinical manifestation of greater biological aging and their presence in the context of a depressive illness exposes elders to deleterious trajectories. Potential common biological substrates that may result in the manifestation of the depressed frail phenotype including mitochondrial functioning, dopaminergic neurotransmission, and inflammatory processes and implications for the assessment and treatment of adults with late-life depression are discussed. As society continues to live longer, the preservation of the quality of these added years becomes paramount, and the combined impact of depression and frailty on the preservation of this quality warrants the attention of clinical researchers and physicians.

Background

Inflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality.

Methods

Longitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression ≥ 10), slow gait (<1.0 m/s), and elevated inflammation (interleukin 6 > 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality.

Results

For each outcome, low-probability (n inflammation = 1,656, n slow gait = 1,471, n depression = 1,458), increasing-probability (n inflammation = 847, n slow gait = 880, n depression = 1,062), and consistently high-probability (n inflammation = 572, n slow gait = 724, n depression = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r = .40, p < .001) and depression (r = .49, p < .001). Although worsening trajectories of inflammation were independently associated with mortality (p < .001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p < .01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations.

Conclusions

Comprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and slow gait speed.

Objective

To determine the effect of the COVID-19 pandemic on the mental health of older adults with pre-existing major depressive disorder (MDD).

Participants

Participants were 73 community-living older adults with pre-existing MDD (mean age 69 [SD 6]) in Los Angeles, New York, Pittsburgh, and St Louis.

Design and measurements

During the first 2 months of the pandemic, the authors interviewed participants with a semistructured qualitative interview evaluating access to care, mental health, quality of life, and coping. The authors also assessed depression, anxiety, and suicidality with validated scales and compared scores before and during the pandemic.

Results

Five themes from the interviews highlight the experience of older adults with MDD: 1) They are more concerned about the risk of contracting the virus than the risks of isolation. 2) They exhibit resilience to the stress and isolation of physical distancing. 3) Most are not isolated socially, with virtual contact with friends and family. 4) Their quality of life is lower, and they worry their mental health will suffer with continued physical distancing. 5) They are outraged by an inadequate governmental response to the pandemic. Depression, anxiety, and suicidal ideation symptom scores did not differ from scores before the pandemic.

Conclusion

Most older adults with pre-existing MDD show resilience in the first 2 months of the COVID-19 pandemic but have concerns about the future. Policies and interventions to provide access to medical services and opportunities for social interaction are needed to help to maintain mental health and quality of life as the pandemic continues.