More time spent sitting or lying down was linked with neurodegeneration and worse cognitive scores in older adults, even among people who were physically active, a 7-year study showed.
In cross-sectional models, greater sedentary time was tied to a smaller Alzheimer's disease-imaging MRI signature (β = -0.0001, P=0.01) and worse episodic memory scores (β = -0.001, P=0.003), reported Angela Jefferson, PhD, of Vanderbilt University Medical Center in Nashville, and colleagues. Cross-sectional outcomes varied by APOE4 status.
In longitudinal analyses, more sedentary time was associated with faster hippocampal volume shrinkage (β = -0.1, P=0.008), and declines in naming scores (β = -0.001, P=0.03) and processing speed scores (β = -0.003, P=0.02; β = 0.01, P=0.01), Jefferson and colleagues said in Alzheimer's & Dementia.
Longitudinal relationships between sedentary time and hippocampal volume remained significant when adjusting for moderate-to-vigorous physical activity (P=0.008), the researchers observed. Longitudinal associations between sedentary time and cognitive scores also remained significant when adjusting for moderate-to-vigorous activity (P<0.03).
"Greater sedentary behavior was associated with smaller hippocampal volume and worse cognitive performance over a 7-year period despite taking into account the level of daily moderate-to-vigorous physical activity each person engaged in," noted co-author Marissa Gogniat, PhD, of the University of Pittsburgh.
"These findings suggest that above and beyond physical activity level, more sedentary behavior is still worse for brain health and cognition over time," Gogniat told MedPage Today.
Many associations linking greater sedentary time with brain health and cognitive outcomes were present in APOE4 carriers but not in non-carriers, suggesting increased sedentary time may be especially harmful for people at increased genetic risk for Alzheimer's disease, she added.
Earlier research from the U.K. Biobank showed that a high level of sedentary behavior among people ages 60 and older was associated with a higher risk of dementia
. Currently, the U.S. POINTER trial is looking at whether simultaneously targeting multiple lifestyle factors in sedentary older adults can reduce cognitive impairment.
Jefferson and colleagues studied 404 participants from the legacy and expansion cohorts of the Vanderbilt Memory and Aging Project, a longitudinal study of older adults without dementia at study entry. Mean baseline age was 71 years; 54% were men and 85% were white. One-third of participants carried at least one APOE4 allele.
The study incorporated actigraphy, neuroimaging, and neuropsychological data collected from participants at multiple intervals. Participants were asked to wear a triaxial accelerometer on their non-dominant wrist 24 hours a day for 10 consecutive days. The researchers calculated average minutes per day spent in sedentary behavior, light physical activity, and moderate-to-vigorous activity for each participant. Sleep time was excluded.
Participants had brain MRI at each timepoint. An Alzheimer's signature was calculated at baseline and at each follow-up, based on measurements from regions of interest previously identified as susceptible to Alzheimer's neurodegeneration.
At each timepoint, participants also completed a comprehensive neuropsychological protocol that included information processing speed, language, executive function, visuospatial ability, and episodic memory tests.
The average follow-up time was 4.7 years. Over the course of the study, 27 participants with data for at least two timepoints converted to dementia.
The average amount of moderate-to-vigorous physical activity time in the cohort was 61 minutes/day. Most participants met the CDC guidelines of at least 150 minutes/week of moderate-to-vigorous physical activity. Moderate-to-vigorous activity was strongly and inversely tied to sedentary behavior (r = -0.65, P<0.0001), and average sedentary time was 807 minutes/day (13.45 hours).
The cohort lacked racial and ethnic diversity and was well educated, Jefferson and co-authors acknowledged.
"In addition, our sample was quite active while wearing the actigraphy devices with 87% of participants meeting the CDC recommendation of at least 150 minutes of moderate-to-vigorous physical activity per week," they noted.
"While such an active sample may limit generalizability, it provides strong evidence that even among a physically active cohort, such increased activity is not protective from the impact of greater sedentary behavior and brain health, especially among APOE4 carriers."
Disclosures
This research was supported by the Alzheimer's Association and the NIH.
Jefferson and Gogniat had no disclosures. One co-author reported a relationship with Vivid Genomics and serving as an editor for Alzheimer's & Dementia.
Primary Source
Alzheimer's & Dementia
Source Reference: Gogniat MA, 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 " Alzheimers Dement 2025; DOI: 10.1002/alz.70157.
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