ObjectivesTo determine the cross-sectional association between cerebral amyloid-beta (A) deposition and gait. DesignCross-sectional. SettingPopulation-based cohort study in Olmsted County, MN. ParticipantsCognitively normal individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of Aging with concurrent PiB-PET imaging and gait assessment. Participants with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic brain injury, or normal pressure hydrocephalus were excluded. MeasurementsPiB-PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor-specific regions of interest (ROIs). Gait parameters (speed, cadence, stride length, double support time, and intra-individual stance time variability) were measured using GAITRite((R)) instrumentation. Linear regression models were adjusted for age, sex, body mass index, education, APOE epsilon 4 allele, Charlson comorbidity index, and depression. In secondary analyses, we additionally adjusted for neurodegeneration (hippocampal volume, FDG PET SUVR, and cortical thickness) in AD-associated regions. ResultsIn fully adjusted models including neuroimaging measures of neurodegeneration, higher PiB-PET SUVR across all ROIs was associated with slower gait speed (P < .05 except for the parietal ROI), lower cadence and longer double support time (P .05 except for the motor ROI), and greater stance time variability (P < .05). In sex-stratified analyses, the association between higher PiB-PET SUVR across all ROIs and measures of gait was only present among women. ConclusionPiB-PET SUVR across ROIs, independent of general measures of AD-associated neurodegeneration, is associated with poorer performance on multiple gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal studies are needed to determine whether A predicts gait decline in both women and men.