Physical Exercise and Longitudinal Trajectories in Alzheimer Disease Biomarkers and Cognitive Functioning

Introduction: Associations of physical exercise with Alzheimer disease (AD) biomarkers and cognitive functioning have been observed cross-sectionally. However, the effects of exercise on longitudinal change in AD biomarkers have not been thoroughly investigated. The current study examined whether individuals with higher baseline exercise exhibited less longitudinal change in AD biomarkers and cognitive functioning, and whetherAPOEand/or brain-derived neurotrophic factor (BDNF) genotypes moderated the effects of exercise on longitudinal changes. Methods: Clinically normal individuals completed a questionnaire on physical exercise over the prior 10-year period at baseline. Ninety-five individuals had serial cerebrospinal fluid samples collected to examine A beta(42), ptau(181)and total tau; 181 individuals underwent multiple assessments of amyloid positron emission tomography imaging with Pittsburgh Compound-B; 327 individuals underwent multiple cognitive assessments, including measures of episodic memory, executive functions, verbal fluency, and processing speed. Results: Greater exercise was associated with less steep decline in processing speed. Baseline exercise did not robustly impact longitudinal change for any other outcomes. NeitherAPOEnorBDNFgenotype robustly moderated the effect of exercise on trajectories of AD biomarkers or cognitive decline. Interpretation: Results suggest that self-reported physical exercise may be limited as a moderator of changes in AD biomarkers.