Background: Amyloid-beta (Aβ) deposition develops decades before clinical Alzheimer's disease (AD) symptoms. Gait abnormalities increase with age and predict cognitive and functional decline, dementia, and death. The effect of Aβ deposition, independent of neurodegeneration, on gait in cognitively normal (CN) individuals is unknown. Methods: We investigated the crosssectional association between continuous PiB-PET SUVR and zscored gait parameters (gait speed, cadence, stride length, double support time, and stance time variability) in 547 CN participants aged 50-69 years enrolled in the Mayo Clinic Study of Aging. Exclusion criteria included a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, normal pressure hydrocephalus, and substantial neurodegeneration (i.e., hippocampal volume<- 2.4cm3, FDG PET SUVR<1.32, or cortical thickness<2.7 mm). We measured Aβ in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor-specific (i.e., PiB-PET averaged across the precentral gyrus, postcentral gyrus, Rolandic operculum, supplementary motor area) regions of interest (ROI). Linear regression models were adjusted for age, sex, body mass index, education, APOE ϵ4, medical comorbidities, and depression. Results: Greater Aβ deposition in all regions was associated with slower gait speed (all p's<0.05 except for the motor ROI), decreased cadence (all p's≤0.001), and increased double support time (all p's<0.02). Higher Aβ deposition, excluding the parietal and motor ROIs, was also associated with greater stance time variability (all p's<0.05). In sex-stratified analyses, higher Aβ deposition in all ROIs was significantly associated with slower gait speed (all p's≤0.01) and cadence (all p's≤0.001), increased double support time (all p's<0.01), and greater stance time variability (all p's<0.05) among women (N=273). We did not observe an association among men (N=274). Conclusions: These findings show that higher levels of brain Aβ deposition across ROIs are associated with worse performance on multiple gait parameters among CN women, aged 50-69 years. Our results suggest that the effects of Aβ on gait appear to be independent of AD-associated neurodegeneration. It is possible that gait measures could be useful for assisting in the screening and identification of CN individuals with significant amyloid for AD preclinical trials. Longitudinal studies are needed to determine whether Aβ predicts gait decline in both women and men.
Wennberg, A. M. V., Savica, R., Hagen, C. E., Roberts, R. O., Knopman, D. S., Jack, C. R., … Mielke, M. M. (2016). P3-268: Cerebral Amyloid Deposition is Associated with Poorer Gait in Cognitively Normal Late-Middle Aged Individuals: the Mayo Clinic Study of Aging. Alzheimer’s & Dementia, 12, P935–P935. https://doi.org/10.1016/j.jalz.2016.06.1931