Increased sedentary behavior is associated with neurodegeneration and worse cognition in older adults over a 7‐year period despite high levels of physical activity

Abstract INTRODUCTION Sedentary behavior may be a modifiable risk factor for Alzheimer's disease (AD). We examined how sedentary behavior relates to longitudinal brain structure and cognitive changes in older adults. METHODS Vanderbilt Memory and Aging Project participants ( n  = 404) completed actigraphy (7 days), neuropsychological assessment, and 3T brain MRI over a 7‐year period. Cross‐sectional and longitudinal linear regressions examined sedentary time in relation to brain structure and cognition. Models were repeated testing for effect modification by apolipoprotein E ( APOE) ε4 status. RESULTS In cross‐sectional models, greater sedentary time related to a smaller AD‐neuroimaging signature (β = ‐0.0001, p  = 0.01) and worse episodic memory (β = ‐0.001, p  = 0.003). Associations differed by APOE ‐ε4 status. In longitudinal models, greater sedentary time related to faster hippocampal volume reductions (β = ‐0.1, p  = 0.008) and declines in naming (β = ‐0.001, p  = 0.03) and processing speed (β = ‐0.003, p  = 0.02; β = 0.01, p = 0.01). DISCUSSION Results support the importance of reducing sedentary time, particularly among aging adults at genetic risk for AD. Highlights Greater sedentary behavior is related to neurodegeneration and worse cognition. Associations differed by APOE ‐ε4 carrier status in cross‐sectional models. Sedentary behavior is an independent risk factor for Alzheimer's disease.