Amyloid burden, a hallmark of Alzheimer’s disease, links to mobility decline in normal aging

Authors

• Q Tian
• SM Resnick
• M Bilgel
• DF Wong
• L Ferrucci
• SA Studenski

Abstract

Older individuals tend to slow down in moving and thinking. We often perceive it as a sign of aging. We rarely think this might be a sign of Alzheimer’s disease (AD). It is only recently that research shows motor slowing strongly predicts risks for cognitive impairment and AD. Initial neuroimaging evidence shows brain atrophy and white matter lesions are associated with poor mobility, which may explain this relationship. Whether amyloid burden, a hallmark of AD, plays a role in mobility decline, independent of memory loss, is unknown. Understanding this relationship is paramount as motor slowing may occur years prior to cognitive symptoms of AD. This study included 59 cognitive normal older participants from the Baltimore Longitudinal Study of Aging who had amyloid imaging in 2006-14, and repeated measures of upper- (mean tapping time) and lower-extremity (gait speed, 400m walk time, Health ABC Physical Performance Battery (HABCPPB) score, balance time) function during follow-up (mean=4.7 years). Higher mean cortical amyloid burden was associated with steeper declines in gait, HABCPPB score, and 400m performance. The relationship was localized in motor planning-related early deposition regions, including putamen, dorsolateral prefrontal cortex, lateral temporal lobe, and precuneus, and not late deposition areas of primary motor cortex or hippocampus. Results remained robust with adjustment for age, sex, body mass index, cardiovascular risk score, APOE ε4 genotype, and concurrent memory decline. These findings show for the first time that amyloid burden is a risk factor for mobility decline among cognitive normal older adults, independent of memory loss.

Scientific Focus Area: Epidemiology

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