Late-Life Physical Activities Moderate the Relationship of Amyloid-β Pathology with Neurodegeneration in Individuals Without Dementia.

Abstract

Physical activities (PA) have been suggested to reduce the risk of Alzheimer's disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited. We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia. This study included participants from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging. Using the multi-modal brain imaging data, in vivo AD pathologies including global amyloid deposition, AD-signature region cerebral glucose metabolism (AD-CM), and AD-signature region cortical thickness (AD-CT) were quantified. Both midlife and late-life PA of participants were measured using the Lifetime Total Physical Activity Questionnaire. This study was performed on 260 participants without dementia (195 with normal cognitive function and 65 with mild cognitive impairment). PA of neither midlife nor late-life showed direct correspondence with any neuroimaging biomarker. However, late-life PA moderated the relationship of brain amyloid-β (Aβ) deposition with AD-CM and AD-CT. Aβ positivity had a significant negative effect on both AD-CM and AD-CT in individuals with lower late-life PA, but those with higher late-life PA did not show such results. Midlife PA did not have such a moderation effect. The findings suggest that physically active lifestyle in late-life, rather than that in midlife, may delay AD-associated cognitive decline by decreasing Aβ-induced neurodegenerative changes in old adults.