Physical Activity as a Modifiable Risk Factor in Preclinical Alzheimer’s Disease

A longitudinal cohort study found that higher objectively measured physical activity was linked to slower cognitive and functional decline in preclinical Alzheimer’s disease, with reduced tau accumulation identified as a key mediator.

The community-based sample included cognitively unimpaired adults with baseline amyloid measures and repeated follow-up using wearable-derived step counts, annual cognitive and functional testing, and longitudinal amyloid and tau PET imaging. Primary endpoints were trajectories of cognition and function plus PET biomarker change.

Higher baseline activity was associated with slower cognitive and functional decline, specifically among participants with elevated baseline amyloid; there was no detectable reduction in amyloid burden with higher activity.

Mediation analyses indicated that a substantial portion of the association between activity and cognition was explained by attenuated tau accumulation. These observational mediation results are consistent with a pathway linking activity to downstream tau dynamics but do not establish causation.

Dose-response analyses suggested thresholds around 5,001–7,500 steps per day correlated with measurable benefit for cognitive trajectories.