Inactivity is associated with worse cognition and neurodegeneration in aging adults

Abstract

AbstractBackgroundGreater physical activity is known to be beneficial for healthier brain aging outcomes. However, less is known about how inactivity might influence the aging brain. Inactivity is highly prevalent in older adulthood and may be an important modifiable risk factor. We examined how inactivity relates to cognitive performance and structural imaging variables in community‐dwelling older adults, particularly among individuals at genetic risk for sporadic AD (i.e., apolipoprotein E (APOE)‐e4 carriers).MethodVanderbilt Memory and Aging Project (n = 265, 74±8 years, 37% female) participants completed at least 7 days of wrist actigraphy, neuropsychological assessment, and 3T brain MRI. Actigraphy data was processed using the GGIR package. Linear regression analyses related average daily minutes spent in inactivity during wake periods to cognition and brain structure adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile score, APOE‐e4 status, cognitive status, actigraphy wear time, and intracranial volume (for MRI outcomes). Models were repeated testing interactions with APOE‐e4 status.ResultThe total sample was inactive for 14±2 hours/day. More minutes of inactivity related to worse episodic memory performance (β = ‐0.001, p = 0.03), a smaller AD‐signature composite of cortical thickness (β = ‐0.0002, p = 0.008), and lower occipital lobe grey matter volume (β = ‐10.01, p = 0.01). Inactivity time interacted with APOE‐e4 status on naming (β = ‐0.01, p = 0.01) and visuospatial performances (β = ‐0.02, p = 0.04); total grey matter volume (β = ‐201.40, p<0.001); and frontal (β = ‐96.24, p = 0.001), temporal (β = ‐27.13, p = 0.03), and parietal lobe volumes (β = ‐54.72, p<0.001). In stratified models, more minutes of inactivity related to worse neuropsychological performance and smaller brain volumes among APOE‐e4 carriers. All stratified models in non‐carriers were null (p‐values>0.12).ConclusionAmong community‐dwelling older adults, more time spent inactive each day related to worse episodic memory performance and lower cortical thickness in regions susceptible to AD‐related neurodegeneration. Results were stronger among APOE‐e4 carriers. This study supports the importance of not just increasing physical activity but also reducing the time spent inactive each day, particularly among aging adults at genetic risk for AD.Funding: IIRG‐08‐88733, P20‐AG068082, R01‐AG034962, K24‐AG046373