Physical activity, biomarkers of brain pathologies and dementia risk: Results from the Memento clinical cohort

Abstract INTRODUCTION This study aims to examine whether physical activity moderates the association between biomarkers of brain pathologies and dementia risk. METHODS From the Memento cohort, we analyzed 1044 patients with mild cognitive impairment, aged 60 and older. Self‐reported physical activity was assessed using the International Physical Activity Questionnaire. Biomarkers of brain pathologies comprised medial temporal lobe atrophy (MTA), white matter lesions, and plasma amyloid beta (Aβ)42/40 and phosphorylated tau181. Association between physical activity and risk of developing dementia over 5 years of follow‐up, and interactions with biomarkers of brain pathologies were tested. RESULTS Physical activity moderated the association between MTA and plasma Aβ42/40 level and increased dementia risk. Compared to participants with low physical activity, associations of both MTA and plasma Aβ42/40 on dementia risk were attenuated in participants with high physical activity. DISCUSSION Although reverse causality cannot be excluded, this work suggests that physical activity may contribute to cognitive reserve. Highlights Physical activity is an interesting modifiable target for dementia prevention. Physical activity may moderate the impact of brain pathology on dementia risk. Medial temporal lobe atrophy and plasma amyloid beta 42/40 ratio were associated with increased dementia risk especially in those with low level of physical activity.