Aerobic Exercise for Optimizing Cognitive and Brain Health In Remitted Late-Life Depression

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ABSTRACT Late-life depression (LLD) increases risk for numerous poor health outcomes in aging, including medical multi-morbidities, disability, and mortality. Importantly, LLD also doubles the risk for dementia relative to the general aging population. Impairment in select cognitive domains (i.e., executive function) persists even after remission of depressive symptoms in LLD. Lifestyle modification is currently the most promising non- pharmacological approach for attenuating cognitive decline in aging and preventing dementia, yet has not been used to target cognitive impairment in remitted LLD (rLLD). Aerobic exercise (AE) is a lifestyle factor that enhances cognitive functioning, with pronounced benefits for executive functioning. AE also influences neuroimaging markers of brain health in regions and networks critical for executive and memory function (i.e., prefrontal cortex, hippocampus, default-mode network). Critically, AE targets cognitive domains and brain regions and networks showing the greatest and most persistent abnormalities in LLD. The goal of the proposed study is to conduct a methodologically rigorous AE trial using comprehensive neuroimaging and neuropsychological approaches to assess the potential of AE training to 1) target systemic brain abnormalities and 2) cognitive deficits; and 3) to explore the extent to which AE effects on neuroimaging markers of brain health relate to its cognitive benefits in those with rLLD. In accordance with the NIMH Experimental Therapeutics approach, this project proposes a 6-month randomized controlled trial comparing moderate-intensity AE to a social engagement (SE) comparison condition, to examine the extent to which AE training influences structural and functional systemic brain abnormalities observed in those with rLLD. The secondary study aim is to examine the direct effect of AE training on cognitive function in those with rLLD. I will also explore the relationship between AE-related brain changes and cognitive improvements to probe neural mechanisms of AE effects on cognition in those with rLLD. The training provided through this award will include 1) building expertise in conducting laboratory- and home-based explanatory exercise interventions in geriatric psychiatric populations; and learning 2) advanced 7T neuroimaging data analytic methods and 3) longitudinal statistical analytic methods. In summary, this K23 study is the first step toward exploring biological mechanisms of the cognitive remediating effects of AE in those with rLLD using an experimental therapeutics approach. The results of this study will provide the necessary preliminary data to support the PI in her efforts to become an independent clinical translational investigator in geriatric behavioral health.