Longitudinal associations between self-reported exercise levels and cognition in ADAD

Introduction: This study examined longitudinal associations between self-reported exercise and cognition, with moderation by sex, in individuals with autosomal dominant Alzheimer's disease (ADAD) mutations. We also examined whether changes in exercise over time differed in ADAD mutation carriers versus non-carriers in the years preceding first cognitive symptom onset. Methods: Participants (n = 491) were ADAD mutation carriers (63%) and non-carriers (37%) from the Dominantly Inherited Alzheimer Network aged 37.6 ± 11.1 years. Participants reported their average time partaking in various leisure-time exercise activities over the past 12 months. Results: Greater baseline exercise predicted better longitudinal cognitive performance. Sex did not moderate these associations. In the years preceding first cognitive symptoms or last follow-up visit, mutation carriers showed a decline in their exercise engagement compared to mutation non-carriers. Discussion: Self-reported exercise is associated with preserved cognitive function in those with ADAD mutations; however, AD-related pathways may influence the level of engagement in exercise prior to cognitive symptom onset. Highlights: Greater weekly exercise predicts slower cognitive decline in ADAD mutation carriers. These associations varied dependent on closeness to estimated symptom onset. These associations were not moderated by sex. Weekly exercise declined in ADAD mutation carriers compared to non-carriers. Results may suggest a bidirectional relationship between exercise and AD risk.