Robert L. Newton - US grants

Project Summary Alzheimer?s disease is steadily increasing in prevalence, with a devastating public health impact. The prevalence of Alzheimer?s Disease is higher in African Americans compared to white Americans, thereby constituting a health disparity. Individuals with mild cognitive impairment (MCI) are at increased risk for progressing to dementia, including AD dementia. Interventions that prevent Alzheimer?s disease or change the course of cognitive decline associated with Alzheimer?s disease are needed. Most older adults do not achieve recommended levels of physical activity, and this includes African Americans. Regular physical activity has proven to be a safe and effective means to enhance cognitive function in older adults with MCI. Therefore, our study is focused on physical activity promotion, a potent approach to modifying multiple neurobiological pathways implicated in Alzheimer?s Disease. We evaluate exercise benefits among elderly African Americans, who are understudied and in whom the natural course of neurodegeneration, exercise effects on neuroprotection and neurodegeneration, and resulting clinical phenotypes may differ. A large body of existing data suggests that exercise improves cardiovascular and cerebrovascular functioning, and thus has the potential to enhance perivascular clearance of amyloid and reduce chronic brain tissue ischemia, among other beneficial effects. At the same time, chronic exercise has been shown to increase central levels of neurotrophic factors, which in turn promote protection against Alzheimer?s Disease neurodegeneration pathways via a variety of mechanisms. While physical activity interventions have been shown to have positive effects on these factors and on resultant cognitive functioning in older adults, nearly all interventions have had a negligible representation of African Americans. Prior data suggests that African Americans enter their elderly years against a backdrop of different lifespan exposures to a variety of factors relevant to neuroprotection and neurodegeneration, including cardiovascular risk, exercise, diet, and education. In addition, prior data suggests that the key genetic risk factor for Alzheimer?s Disease (APOE) may have differing consequences for Alzheimer?s Disease risk among African Americans, and other genetic differences (i.e. leucocyte telomere length) have the potential to influence the brain benefits of physical activity in this community. We will utilize a randomized clinical trial to addresses these questions. Participants will be randomized into a physical activity promotion intervention or an active control group for 52 weeks. We will recruit a population with MCI. We will assess cognitive function, brain structure and function, circulating hormones, neurotrophic factors, objectively measured physical activity, cardiorespiratory fitness, sleep parameters, and telomere length. Our study will take the first step toward understanding whether the hypothesized benefits of exercise for the brain carry over to elderly African Americans with MCI.