Precision Medicine in Alzheimer's Disease: A SMART Trial of Adaptive Exercises and Their Mechanisms of Action Using AT(N) Biomarkers to Optimize Aerobic-Fitness Responses

What this Trial Is About

Researchers are evaluating the effects of six months of aerobic exercise on older adults aged 65 years or older who have mild cognitive impairment (MCI) or probable/possible mild Alzheimer's disease (AD). This Phase II mechanistic Sequential, Multiple Assignment, Randomized Trial (SMART) aims to assess how aerobic exercise influences aerobic fitness, brain white matter changes, and patient-centered outcomes. The study also seeks to identify the best exercise approaches to improve aerobic fitness and understand how exercise impacts memory mechanisms in early AD. Participants are assigned to one of several exercise programs: moderate intensity continuous training (MICT) cycling for 30-50 minutes three times a week, chair-based stretching for 30-50 minutes three times a week, a combination of MICT followed by high-intensity interval training (HIIT) cycling for 40 minutes three times a week, or MICT followed by strength-building exercises three times a week for three months. The study includes an initial 3-month exercise phase with possible adaptation based on fitness response, lasting up to six months. During the study, participants will undergo cognitive testing and exercise assessments five times over one year, brain MRI scans three times in the same period, and monthly follow-ups discussing health and wellness. Researchers will measure peak oxygen consumption and white matter hyperintensity volume at baseline and six months, along with memory, physical function, behavioral symptoms, caregiver burden, quality of life, and blood biomarkers over one year. The trial includes safety monitoring and aims to improve understanding of exercise effects on early Alzheimer's disease.

A SMART Trial of Adaptive Exercises to Optimize Aerobic-Fitness Responses