Lifetime walking and Alzheimer’s pathology: A longitudinal study in older adults

J Prev Alzheimers Dis. 2025 May 16:100203. doi: 10.1016/j.tjpad.2025.100203. Online ahead of print.

ABSTRACT

IMPORTANCE: While many studies have shown that greater amounts or longer durations of walking are associated with a lower risk of Alzheimer’s disease (AD) or cognitive decline in older adults, the neuropathological basis for this is not yet fully understood.

OBJECTIVE: To examine the relationship between walking intensity and duration and longitudinal changes in Alzheimer’s disease (AD)-related brain pathologies, including Aβ and tau accumulation, neurodegeneration, and white matter hyperintensity (WMH).

DESIGN: Data were drawn from the Korean Brain Aging Study for the Early Diagnosis and Prediction of AD, a longitudinal cohort study (initiated in 2014).

SETTING: Community and memory clinic setting.

PARTICIPANTS: One hundred fifty-one older adults.

MAIN OUTCOME AND MEASURES: Participants underwent baseline and 4-year follow-up neuroimaging assessments. Lifetime walking, as measured using the Lifetime Total Physical Activity Questionnaire, was categorized by intensity (high vs. low) and duration (short ≤360 min/week vs. long >360 min/week), forming four combined walking groups. Aβ and tau deposition, neurodegeneration, and WMH volume were assessed via PET/MRI.

RESULTS: Long-duration or high-intensity walking was associated with significantly reduced Aβ accumulation over 4 years. The high-combined walking group showed similar benefits, while medium-combined groups did not. The effect was significant only in the early life-initiated walking subgroup. No associations were found with tau, neurodegeneration, or WMH volume.

CONCLUSIONS: Long-duration, high-intensity walking may reduce brain Aβ accumulation, potentially lowering AD risk, particularly when initiated before late life.

PMID:40382248 | DOI:10.1016/j.tjpad.2025.100203