Objective physical activity and Alzheimer's disease burden in the population‐based Rotterdam Study

INTRODUCTION Physical activity is linked to lower dementia risk, but its connection to Alzheimer's disease (AD) pathology remains uncertain. This study examined the relationship between objectively measured physical activity and early AD biomarkers in cognitively unimpaired adults. METHODS Accelerometer‐measured physical activity and plasma AD biomarkers (beta‐amyloid [Aβ]42/Aβ40, p‐tau217) were assessed in 242 participants (age = 63.37 [54–79] years) of the population‐based Rotterdam Study. Cortical Aβ was assessed via 18 F‐florbetaben positron emission tomography (PET) 7 years later. Robust regression assessed the relationship between physical activity, plasma AD biomarkers, and Aβ PET burden, while compositional analysis examined how the time‐use composition relates to AD outcomes. RESULTS Physical activity was not associated with plasma Aβ42/Aβ40, p‐tau217, or brain Aβ burden 7 years later. Reallocating awake sedentary time to physical activity showed no association with AD biomarkers. DISCUSSION No relationship was identified between physical activity and AD biomarkers, suggesting physical activity might affect dementia risk through other pathways or in an earlier life phase. Highlights Physical activity was not associated with plasma beta‐amyloid (Aβ)42/Aβ40 nor p‐tau217. No association was observed between physical activity and brain Aβ 7 years later. Age, sex, and apolipoprotein E ε4 carriership did not moderate these relationships. Reallocating 30 minutes of sedentary time to physical activity resulted in no change in Alzheimer's disease (AD) biomarkers.