Examining the Persistence of Neurocognitive Benefits of Exercise

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Project Summary/Abstract Physical activity (PA) is one of the most promising approaches for mitigating age-related cognitive decline and risk for dementia, yet few sufficiently powered randomized clinical trials (RCT) targeting brain health outcomes have been conducted. Further, little is known about the biological pathways and moderators of the brain response to exercise. To address these gaps, we have conducted a multi-site, supervised, dose-response (150min/wk of moderate-intensity; 225min/wk of moderate-intensity; 150min/wk of light intensity), aerobic exercise RCT with brain health outcomes as the primary endpoints in 648 cognitively normal adults between 65-80 years of age. This study, Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE), was funded by the NIH in 2016. The RCT has been enormously successful in terms of exceeding sample size expectations, maintaining high adherence and compliance (>80%), minimal missing data, improving cardiorespiratory fitness, and achieving the expected distribution of under-represented minorities (25% non-white). The results from IGNITE are bound to be transformative, but there will remain many unanswered questions after the conclusion of IGNITE that we intend to address in this proposal. For example, does a 12-month aerobic exercise RCT have any persistent or protracted benefits to cognitive, neural, or neuropathological outcomes 5-years after the completion of the intervention? Was the RCT effective at modifying long-term exercise behaviors? Can we utilize the rich participant data of IGNITE to forecast who is more likely to maintain a physically active lifestyle after the completion of the intervention? How effective was the exercise RCT for modifying the accumulation of Alzheimer’s disease (AD) neuropathology over a 5-year follow-up? And, finally, if cognitive, brain, or markers of neuropathology are different as a function of group assignment 5-years after the completion of the intervention, which factors mediate those long-term benefits? The answers to these questions will have significant scientific and public health implications that we will address in a cost-effective manner by conducting a 5-year follow-up evaluation of IGNITE participants. We focus on 4 key aims and one discovery science aim: Aim 1: Test the effects of the IGNITE exercise RCT on cognitive performance 5-years after the completion of the intervention. Aim 2: Examine the extent to which participants maintained exercise behaviors 5-years after the completion of the intervention. Aim 3: Test whether the intervention modified 5-year accumulation of AD neuropathology. Aim 4: Test whether the exercise RCT influenced 5-year follow-up of neuroimaging markers of brain health. Discovery Science Aim: Explore whether participant characteristics at baseline predict long-term engagement in exercise behaviors after the completion of the intervention.