The apolipoprotein E epsilon 4 (APOE ?4) allele is the most important genetic risk factor for late onset Alzheimer's disease (AD). A recent review by the World Health Organization highlighted the potential protective role of physical activity and exercise against cognitive decline, all-cause dementia, AD, and vascular dementia in healthy individuals. In an 18-month longitudinal observational study, we showed that sedentary ?4 carriers experience significant declines in episodic memory and hippocampal volume compared to ?4 carriers who engaged in moderate PA. Importantly, among ?4 non-carriers, no significant longitudinal changes in cognition and brain imaging were observed whether the non-carriers were sedentary or engaged in moderate PA, suggesting that PA has a specific neuroprotective role in delaying the progression of AD in ?4 carriers. Based on our results, a pragmatic, randomized controlled trial with blinded clinical and imaging outcomes is proposed to determine the impact of a home based, high intensity exercise intervention in healthy, cognitively intact ?4 carriers between the ages of 65 and 80 years. The CYCLE-AD (CYcling to Cease or Limit the Effects of Alzheimer's Disease) trial will recruit otherwise healthy sedentary carriers randomized to one of two groups (n=75 each): 1) an Indoor Cycling (IC) group that participates in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton cycling system or 2) a Usual and Customary Care (UCC) group, in which participants engage in their habitual level of PA. We hypothesize that an 18-month high-intensity aerobic exercise regimen will slow AD-related disease progression in sedentary elders at genetic risk for AD. Participants in the intervention group will engage in exercise 3x/week (minimum 90 minutes/week) for 18 months. Primary outcome measures, obtained at study entry and at 18 months, will include comprehensive cognitive testing and brain MR imaging to assess disease progression and a comprehensive PA/fitness assessment to measure the degree of change in physical fitness due to high intensity aerobic exercise. The overall goal of the CYCLE-AD trial is to determine the role of long-term, high intensity exercise in slowing or delaying the onset of cognitive and AD-related brain changes in ?4 carriers. Successful translation and demonstration of the effectiveness of a scalable home-based exercise intervention capable of slowing or delaying disease onset will transform AD treatment, improve patient outcomes and quality of life, and reduce health care costs.
This project will determine the disease altering properties of high intensity exercise by randomizing 150 cognitively intact, sedentary elders (ages 65-80 years) at genetic risk for Alzheimer's disease into two groups: one engaged in a high-intensity home-based cycling program and the other engaged in their habitual level of physical activity. Both groups will be monitored over an 18-month period with cognitive testing and MRI brain scans serving as primary outcomes to determine the disease altering characteristics of aerobic exercise. Successful translation and demonstration of the effectiveness of a scalable home-based exercise intervention capable of slowing disease course will transform AD treatment, improve patient outcomes and quality of life, and reduce health care costs.
