β-amyloid burden predicts lower extremity performance decline in cognitively unimpaired older adults

Background: Motor slowing is associated with risk of Alzheimer's disease. Whether β-amyloid (Aβ) burden is associated with motor decline, independent of cognitive decline, is unknown. Methods: About 59 cognitively unimpaired older participants had baseline PET-PiB scans and repeated measures of lower (usual gait speed, 400-m time, Health ABC Physical Performance Battery (HABCPPB) score, total standing balance time) and upper (mean tapping time) extremity performance during a mean follow-up of 4.7 years. Linear mixed effect models examined the relationship between baseline Aβ burden and motor decline, adjusting for age, sex, body mass index, cardiovascular risk, APOE ϵ4 status, memory decline, depressive symptoms, ankle-arm index, processing speed, executive function, and cerebrovascular disease. Results: Higher mean cortical Aβ burden was associated with greater declines in gait speed and HABCPPB score and a greater increase in 400-m time. Higher Aβ of putamen was associated with declines in all lower extremity measures, including balance. Higher Aβ of dorsolateral prefrontal cortex and lateral temporal lobe was associated with declines of gait speed and 400-m time, and of precuneus with a greater increase in 400-m time. Associations remained similar after further adjustment. Conclusions: In cognitively unimpaired older adults, Aβ burden overall and in specific brain regions are risk factors for lower extremity motor decline, independent of memory function. These findings provide the first empirical evidence that Aβ burden is a risk factor for mobility decline in older adults.