The unprecedented growth of the elderly population and subsequent increase in age-related disorders requires effective strategies for promoting healthy brain aging. Accumulating evidence suggests that aerobic exercise may protect against cognitive decline and dementia. Although there is consensus that current recommendations (~ 30 minutes of exercise most days of the week) provides general health benefits to older adults, there is a need for rigorous clinical trial data to guide exercise prescription specific to the older adult population. For instance, unlike with prescription drugs, the minimum and maximum effective exercise doses are not well defined for general health effects. Moreover, the dose-response relationship between exercise and cognition has not been examined in randomized trials. Thus, there remains a need for rigorous, well- designed clinical trials to define the long-term benefits of exercise in promoting healthy brain aging and preventing cognitive and functional decline. We will examine the benefits of three doses of aerobic exercise (representing 50%, 100%, and 150% of the recommended dose) on aerobic fitness, physical function, and cognition. Sedentary, older adults with cognitive complaints aged 75 and over (n = 100) will be randomized into a non-exercise control group or one of three exercise dose groups for 26 weeks. Exercise dose will be manipulated by duration of exercise (as opposed to intensity). Supervised exercise will occur within the network of Greater Kansas City YMCAs, building on our group's history of NIH-funded collaborations with the community. Our objective is to establish feasibility of a long-term exercise intervention to remediate age-related cognitive decline. We hypothesize that increasing exercise doses will provide greater cognitive, aerobic fitness and physical function benefits. Our primary goal is to determine the optimal exercise dose for maximizing exercise-related gains in 1) cognition, 2) aerobic fitness and 3) adherence in this vulnerable population for planning a more definitive study. Aim 1 will examine the dose-response of aerobic exercise on cognitive function and provide expected cognitive effect sizes for each dose to inform the design of a large, definitive trial. Aims 2 and 3 will assess physiologic adaptations including aerobic fitness and measures of physical function. The current project is a natural extension of a programmatic line of investigation developed by the KU Alzheimer and Memory Program. The pilot study will generate important data regarding the magnitude of exercise-related effect sizes and dose-response trends for cognitive, aerobic fitness and physical function changes. This data will inform the choice of the most effective and feasible exercise dose in older adults for a more definitive trial. PUBLIC HEALTH RELEVANCE: The unprecedented growth of the elderly population and subsequent increase in age-related disorders requires effective strategies for promoting healthy brain aging. Accumulating evidence suggests that aerobic exercise may protect against cognitive decline and dementia, yet there remains a need for rigorous, well-designed clinical trials to define the long-term benefits of exercise for promoting healthy brain aging. A primary goal of the current study is to define an optimal dose of exercise in older adults 75 years and older. The current study will provide important public health information regarding fundamental questions about exercise in delaying age-related cognitive and functional decline.