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Depression has been shown to negatively impact neurocognitive functions, particularly those governed by fronto-subcortical networks, such as executive functions. Converging evidence suggests that depression-related executive dysfunction is greater at older ages, however, this has not been previously confirmed by meta-analysis. We performed a systematic review and meta-analysis, using three-level models, on peer-reviewed studies that examined depression-related differences in cognitive control in healthy community-dwelling individuals of any age. We focused on studies of cognitive control as defined by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which centers on goal-directed behavior, such as goal selection (updating, representations, maintenance), response selection (inhibition or suppression), and performance monitoring. In 16,806 participants aged 7 to 97 across 76 studies, both clinical depression and subthreshold depressive symptoms were associated with cognitive control deficits (Hedges’ g = -0.31). This relationship was stronger in study samples with an older mean age. Within studies with a mean age of 39 years or higher, which represents the median age in our analyses, the relationship was stronger in clinical compared to subthreshold depression and in individuals taking antidepressant medication. These findings highlight the importance of clinicians screening for cognitive control dysfunction in patients with depression, particularly in later stages of adulthood.

Both clinical depression and subthreshold depressive symptoms have been associated with alterations in cortical thickness. Studies have yielded conflicting results regarding whether cortical thinning or cortical thickening best characterize the depressive state. Also unclear is whether cortical thickness differences are lateralized. This study examined the relationship between depressive symptom dimensions and cortical thickness asymmetry in cingulate and orbitofrontal regions. Fifty-four community-dwelling adults between the ages of 18 and 81 years received a 3-Tesla magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Cortical thickness values were extracted for the rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, isthmus cingulate, and orbitofrontal cortex. An asymmetry index was calculated for each region. Data were analyzed using separate general linear models for each region, in which the CES-D somatic symptoms, negative affect, and anhedonia subscale scores predicted the asymmetry indices, controlling for age and sex. Higher scores on the anhedonia subscale were associated with right-sided asymmetry in orbitofrontal thickness, whereas higher somatic symptom subscale scores predicted greater left-sided asymmetry in posterior cingulate thickness. Follow-up analyses showed the orbitofrontal effect was specific to the medial, not the lateral, orbitofrontal cortex. These results suggest asymmetries in cortical thickness are apparent at even subthreshold levels of depressive symptoms, as all but five participants were below the CES-D cutoff for clinical depression, and that the relationship varies for different symptom dimensions of depression. Understanding brain asymmetries across the range of depressive symptom severity is important for informing targeted depression treatment.

Objective:To lay out the argument that exercise impacts neurobiological targets common to both mood and cognitive functioning, and thus more research should be conducted on its use as an alternative or adjunctive treatment for cognitive impairment in late-life depression (LLD).Method:This narrative review summarizes the literature on cognitive impairment in LLD, describes the structural and functional brain changes and neurochemical changes that are linked to both cognitive impairment and mood disruption, and explains how exercise targets these same neurobiological changes and can thus provide an alternative or adjunctive treatment for cognitive impairment in LLD.Results:Cognitive impairment is common in LLD and predicts recurrence of depression, poor response to antidepressant treatment, and overall disability. Traditional depression treatment with medication, psychotherapy, or both, is not effective in fully reversing cognitive impairment for most depressed older adults. Physical exercise is an ideal treatment candidate based on evidence that it 1) is an effective treatment for depression, 2) enhances cognitive functioning in normal aging and in other patient populations, and 3) targets many of the neurobiological mechanisms that underlie mood and cognitive functioning. Results of the limited existing clinical trials of exercise for cognitive impairment in depression are mixed but overall support this contention.Conclusions:Although limited, existing evidence suggests exercise may be a viable alternative or adjunctive treatment to address cognitive impairment in LLD, and thus more research in this area is warranted. Moving forward, additional research is needed in large, diverse samples to translate the growing research findings into clinical practice.

Objective:The world population is rapidly aging, and consequently, cognitive decline is becoming a larger public health crisis. There is no cure for dementia, but exercise has been consistently shown to improve cognitive function and slow cognitive decline in older adults. Given the many barriers to starting an exercise routine, walking is a particularly appealing intervention because it is safe, low-impact, and highly accessible (i.e., no upfront costs, no necessary equipment, and can be done almost anywhere and by anyone, given they are ambulatory). This abstract describes a systematic review and meta-analysis on peer-reviewed studies that examined randomized walking interventions for cognitive function in older adults.Participants and Methods:The analyses included 1,286 older adults aged 55 and older (mean age = 73.1 years) across 19 studies that met inclusion criteria. All studies were randomized controlled trials (RCTs) of walking interventions with pre-post cognitive outcome data. A total of eight cognitive domains were identified: global cognition, attention, processing speed, working memory, language, visuospatial skills, declarative memory, and executive function. Effect sizes, measured as net treatment gain, were extracted and converted to Hedges’ g. Three-level meta-analysis was used to account for dependency of effect sizes. Meta-regression analyses were used to examine whether the following variables moderated effect sizes: (a) cognitive status, (b) baseline activity level, (c) age, (d) walking intervention duration, and (e) duration of individual walking sessions.Results:Participation in walking interventions significantly benefitted broad cognitive functioning (Hedges’ g = 0.19). The cognitive domains that specifically benefitted from walking were global cognition (g = 0.60), processing speed (g = 0.15), working memory (g = 0.22), declarative memory (g = 0.18), and executive functioning (g = 0.15). Cognitive status moderated this relationship, so that cognitively impaired older adults showed greater cognitive benefit from walking interventions. Baseline activity level did not moderate the effect; being sedentary at baseline yielded an effect size significantly greater than zero. The remaining moderator analyses were nonsignificant.Conclusions:This systematic review and meta-analysis shows that walking interventions are associated with broad improvement in cognitive function in older adults. Walking benefits global cognition, processing speed, working memory, declarative memory, and executive function— the same cognitive domains that decline with normal cognitive aging. These findings are particularly important because walking is among the safest and most universally accessible forms of exercise. This will help healthcare providers make better lifestyle recommendations to their older patients. Future research should more rigorously examine potential moderating variables, such as walking intensity.