There are no effective therapeutic options to delay the progression of Alzheimer's disease. The benefits of exercise on brain in older adults at high risk for dementia have become an important therapeutic focus, and now there is an urgent need to demonstrate effectiveness in a large diverse population using accessible, cost-effective, and sustainable programs that can be readily implemented in community settings. The Alzheimer's Disease Cooperative Study (ADCS) and Wake Forest School of Medicine have partnered with the YMCA of the USA (Y-USA) to conduct a Phase 3 randomized controlled 18-month trial to test whether moderate-high intensity aerobic exercise can slow disease progression in 300 sedentary older adults with mild cognitive impairment (MCI). The study (“EXERT”) is conducted at 14 sites nationwide, and participants complete their exercises at selected YMCAs under the supervision of a study-certified trainer in the first 12 months, and independently in the final 6 months. Protocols were developed to provide education to trainers about MCI and personalized exercise prescriptions that can be readily implemented. EXERT participants are randomized to an aerobic training or control group. Both groups exercise for 45 minutes 4 days per week for 18 months at the YMCA. Aerobic training consists of treadmill walking at 70–80% heart rate reserve (HRR), while the control group completes stretching/balance/range of motion exercises while maintaining HRR <35%. Protocols to encourage adherence rely on a diverse support system provided by the trainers/staff to provide health education, regular encouragement, and reinforcers when goals are met. Outcomes include cognition, functional status, specimen biomarkers, brain imaging, and sleep actigraphy. Intervention effects on quality of life for participant and study partner will be examined. The study design, recruitment approach, implementation of the intervention, and partnership with the Y-USA will be described. The strong collaborative relationship between a highly effective and visible community organization and academic research institutions provide the essential infrastructure to support rapid translation of new discoveries into widespread community practice. EXERT, if successful, may identify an AD-slowing exercise prescription that can be readily implemented and sustained using an existing well-established national platform for community exercise.