Project Summary Older adults often experience physical decline that can be directly ameliorated by physical activity and exercise. Evidence is building that exercise prevents cognitive decline or delays the onset of debilitating dementia (e.g. Alzheimer's disease [AD]) yet, the optimal dose and combination of exercise modalities for promoting brain health, however, remains unknown and essentially untested. Our long-term research goal is to develop and test strategies to support successful aging and prevent AD. We have successful ongoing (R01AG053312, R01AG053952, R01AG049749, R01AG52954, R01AG043962) and completed projects (R01AG033673, R01AG034614, KL2TR000119) around a theme of community-based exercise programs for older adults. We will enroll 280 individuals, age 65 to 80 years without cognitive impairment, into a 52-week exercise intervention to test the combined and independent effects of aerobic and resistance training on cognition, brain structure, and physical function. We will also explore underlying biological mechanisms that may link exercise with brain health. Participants will be randomized into 1 of 4 groups: flexibility, toning and balance (control), aerobic exercise training, progressive resistance training, or combined aerobic and resistance training. All intervention groups represent the most common modalities of exercise and directly reflect the public health recommendations for aerobic and resistance training. Exercise training will occur in a community setting through the network of Greater Kansas City YMCAs. We hypothesize that 52 weeks of exercise will improve 1) cognitive performance, 2) regional brain volume, 3) cardiorespiratory fitness and strength 4) biomarkers. This will be the largest study to assess the combined and independent effects of the two most recommended forms of exercise. Demonstrating specific exercise effects on cognitive function and brain health in older adults would have enormous public health implications. The study's results will also impact public health policy and education by providing evidence towards the specific or synergistic effects of aerobic and resistance training on cognition and brain structure. Encouraging the public to adapt more active lifestyles and stimulate the development of effective exercise delivery programs to enhance initiation and maintenance of physical activity interventions is key to increasing the number of quality years of life for America's aging population.