THE POTENTIAL ROLE OF EXERCISE IN DELAYING GENETIC DESTINY: EXAMINING THE RELATIONSHIP BETWEEN EXERCISE AND KEY BIOMARKERS IN DOMINANTLY INHERITED ALZHEIMER’S DISEASE

Abstract

INTRODUCTION Greater physical activity is associated with reduced risk for Alzheimer’s disease (AD), and lower levels of AD-related biomarkers, such as beta-amyloid (Aβ) and tau, measured in the cerebrospinal fluid (CSF) and brain. A small proportion of Alzheimer’s disease (<1%) cases are caused by a rare dominant genetic mutation. The aim of the current study was to examine associations between self-reported exercise participation and AD-related biomarkers (from CSF and brain imaging) over time, in individuals we know will develop Alzheimer’s disease at an early age (i.e., dominant AD mutation carriers). METHODS The sample included n = 308 mutation carriers from the Dominantly Inherited Alzheimer’s Network (DIAN) study with data available for self-reported exercise participation, brain imaging (hippocampal volume, total brain volume, gray matter volume, white matter hyperintensities, brain Aβ levels), and biomarkers quantified from CSF (several Aβ and tau species and ratios). Participants were assessed regularly (time interval depending on mutation type) from baseline to 10+ years post-baseline. Associations between exercise and AD biomarkers (i.e., from brain imaging and CSF) were examined using linear mixed models, corrected for various confounding variables. RESULTS The sample had a mean age of 39.7 ± 10.8 years and were 56% female. Greater baseline exercise was associated with a slower decrease in right (B=0.06, p < 0.001) and left (B=0.06, p<0.05) hippocampal volume; and slower accumulation of brain Aβ (B=0.04, p<0.001). CONCLUSION These findings demonstrate that exercise is associated with more favourable profiles of AD-related biomarkers in those with ADAD mutations. This work may have implications for our understanding of how exercise influences disease development in late-onset sporadic AD. Nevertheless, the causal direction of our findings is difficult to ascertain, and future study designs investigating the therapeutic potential of exercise in both ADAD and late-onset AD should be considered.