Dementia Risk and Dynamic Response to Exercise: Methodology for an Acute Exericise Clinical Trial

Background: Exercise likely has numerous, meaningful benefits for brain and cognition. However, those benefits and their causes remain imprecisely defined, especially in the context of cognitive disorders associated with aging, such as Alzheimer disease (AD). If the brain does benefit from exercise it does so primarily through exposure to brief, acute exposures to exercise over a lifetime. Methods: The Dementia Risk and Dynamic Response to Exercise (DYNAMIC) clinical trial seeks to characterize the acute exercise response in cerebral perfusion, and circulating neurotrophic factors in older adults with and without the apolipoprotein e4 genotype (APOE4), the strongest genetic predictor or sporadic, late onset AD. DYNAMIC will enroll 60 older adults into a single moderate intensity bout of exercise intervention. We will measure pre- and post-exercise cerebral blood flow using arterial spin labeling, and neurotrophic factors. We expect that APOE4 carriers will have poor CBF regulation, i.e. slower return to baseline perfusion after exercise, and will demonstrate blunted neurotrophic response to exercise, with concentrations of neurotrophic factors positively correlating with CBF regulation. If exercise-induced changes in perfusion and circulating factors can be detected, DYNAMIC will contribute to our understanding of exercise-induced brain change and potential biomarker outcomes of exercise interventions. Results: Preliminary proof-of-concept findings on 7 older adults and 9 younger adults. We have found that this experimental method can capture CBF and neurotrophic response over a time course, and best practices following exercise. Conclusions: This methodology will provide important insight into acute exercise response and potential directions for clinical trial outcomes. ClinicalTrials.gov NCT04009629