Greater Sedentary Time Leads to Worse Cognition, Increased Neurodegeneration

Angela L. Jefferson, PhD

Published findings using participants from the Vanderbilt Memory and Aging Project revealed that greater sedentary time, or waking hours spent in non-movement, leads to increased neurodegeneration and worse cognition, particularly for adults at genetic for Alzheimer disease. Overall, these findings support the importance of reducing sedentary time, which may be seen as an independent risk factor for AD.¹

The longitudinal study featured 404 patients aged 50 and older who were cognitively unimpaired or met existing criteria for early mild cognitive impairment (eMCI). Participants were followed serially at 5-year (2017-2019), 7-year (2019-2021), 9-year (2021-2023), and 11-year (2023-ongoing) intervals, undergoing neuropsychological assessments and 3T brain MRI over a 7-year period within.

In the study, patients were asked to wear a triaxial accelerometer on their non-dominant wrist 24h per day for 10 consecutive days. The thresholds for wrist actigraphy variables in community-dwelling adults were calculated as follows: (1) sedentary behavior ≤49 mg; (2) light physical activity (LPA) 50-99 mg; and (3) moderate-to-vigorous physical activity (MVPA) ≥100 mg. Sleep periods were detected by GGIR and excluded from quantifications of sedentary behavior and physical activity.

Led by Angela L. Jefferson, PhD, the Herbert O. and Vineta Christopher Director in Alzheimer’s Disease at Vanderbilt Memory and Alzheimer’s Center, cross-sectional and longitudinal linear regressions examined sedentary time in relation to brain structure and cognition. Inn cross-sectional models, greater sedentary time related to a smaller AD-neuroimaging signature (ß = –0.0001; P = .01) and worse episodic memory (ß = –0.001; P = .003). The association between sedentary time and worse episodic memory remained statistically significant when excluding outliers (P = .03) but not when adjusting for MVPA (P = .19).

"These findings are particularly important in the context of aging, as mobility limitations and greater sedentary time increases in older adults." Jefferson et al wrote. "This study also contributes novel and preliminary information to our understanding of how sedentary behavior may interact with genetic risk for AD. From a personalized medicine approach, healthcare professionals might consider assessing not only a patient's exercise regimen but also the amount of time they are sedentary throughout the day, recommending a reduction in such sedentary behavior in addition to increasing daily physical activity."

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In stratified models, among APOE-ε4 carriers, or those with the highest AD risk, greater sedentary time was cross-sectionally associated with lower total gray matter volume (ß = –75.8; P = .02) and smaller frontal (ß = –38.0; P = .02) and parietal lobe volumes (ß = –18.5; P = .03). These effects remained statistically significant when adjusting for MVPA except or total gray matter volume. Notably, all stratified models in non-carriers were not statistically significant (P values >.10).

In cross-sectional analyses, sedentary time interacted with APOE-ε4 carrier status on measures of language and visuospatial performance. Higher sedentary time was linked to poorer scores on the Boston Naming Test (ß = –0.01; P = .01) and Hooper Visual Organization Test (ß = –0.01; P = .01), with results remaining significant after adjustment for MVPA (P = .01) and removal of outliers (P <.02). Stratified analyses showed the relationship between sedentary time and visuospatial performance was present only among APOE-ε4 carriers (β = –0.01; P = 0.03), persisting after excluding outliers (P = 0.009) but not after adjusting for MVPA (P = 0.32).

Longitudinal models indicated that greater sedentary time predicted declines in naming (β = –0.001; P = 0.03), processing speed via WAIS-IV Coding (β = –0.003; p = 0.02), and executive function speed on D-KEFS Number Sequencing (β = –0.01; p = 0.01). These associations were robust to MVPA adjustment (P < 0.03) and remained after excluding outliers (P < 0.04), except for naming (P > 0.13). No longitudinal interactions with APOE-ε4 carrier status were observed (P > 0.08).

Jefferson and the study authors concluded that, "this study contributes to our understanding of how greater sedentary behavior is associated with AD-related neurodegeneration and cognition changes. Future work may consider exploring the underlying biological mechanisms that contribute to these associations, which could inform treatment and prevention efforts."

REFERENCE
1. Gogniat MA, Khan OA, Li J, et al. Increased sedentary behavior is associated with neurodegeneration and worse cognition in older adults over a 7-year period despite high levels of physical activity. Alzheim Assoc. 2025;21(5):e70157. doi:10.1002/alz.70157