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.

Keywords: Alzheimer's disease; brain health; cognition; sedentary.