(Photo by Krakenimages.com on Shutterstock)
In a nutshell
- Older adults who sat longer each day showed faster brain shrinkage, even if they exercised regularly.
- Sitting time was linked to worse memory and cognitive performance, especially in people with the APOE-ε4 gene.
- Spending less time sitting may protect your brain as much as adding more exercise.
NASHVILLE — Are you reading this while lounging on your couch? You might want to stand up. New research shows that too much sitting could damage your brain, regardless of your exercise habits.
A study spanning seven years found that older adults who spent more hours sitting experienced faster brain shrinkage and mental decline – even among those who regularly worked out.
This finding challenges what many people believe: that regular exercise makes up for hours of sitting. According to the research, most participants were active enough to meet CDC guidelines for weekly physical activity. Yet their sedentary behavior still harmed their brain health.
The Hidden Cost of Being Sedentary
Researchers from Vanderbilt University’s Memory and Alzheimer’s Center followed 404 older adults (average age 71) for seven years, using wrist-worn activity monitors to accurately track movement patterns. On average, participants sat for about 13 hours daily – a number that might seem high until you add up your own sitting time from commuting, desk work, meals, and evening relaxation.
The brain changes linked to more sitting occurred in regions that are typically vulnerable to Alzheimer’s disease. People who sat more showed thinning in these areas and performed worse on memory tests that asked them to recall past experiences and events.
Over time, those who sat more lost hippocampal volume faster and showed greater declines in their ability to name objects and process information quickly. The hippocampus, which helps form memories, is among the first brain regions affected by Alzheimer’s disease.
Going straight from a desk job to the couch every day could lead to brain shrinkage linked to dementia, research shows. (Photo by Stokkete on Shutterstock)
Genetic Risk Factors Amplify the Problem
Most concerning was that sitting had worse effects on carriers of the APOE-ε4 gene variant, which increases Alzheimer’s risk. When researchers separated participants by genetic status, they discovered that APOE-ε4 carriers who sat more showed significantly greater reductions in total brain matter, frontal lobe volume, and parietal lobe volume compared to non-carriers with similar sitting habits.
The study, published in Alzheimer’s & Dementia, found that “APOE-ε4 carriers appear to be at increased risk for neurodegeneration associated with greater sedentary behavior, independent of physical activity level.”
While previous studies have connected too much sitting with heart disease, diabetes, and cancer, this research strengthens the evidence that brain health belongs on that list. Researchers believe that prolonged sitting may harm blood vessels in the brain, increase inflammation, and reduce connections between brain cells.
How the Study Worked
The research team used advanced equipment that measured movement 30 times per second. This allowed them to distinguish between sitting still, light activity like casual walking, and more vigorous movement far more accurately than asking people to recall their activity levels.
Each participant completed extensive cognitive testing and underwent detailed brain scans at the beginning of the study and during follow-up visits. Researchers analyzed various brain regions and something they called an “AD-neuroimaging signature” – a measurement of brain thickness in areas typically affected by Alzheimer’s.
What makes this study particularly valuable is that it controlled for physical activity, allowing researchers to isolate the specific effects of sitting. This reveals that even if you follow exercise guidelines religiously, spending most of your remaining hours sitting could still harm your brain.
Protecting Your Brain Health
With smartphones and artificial intelligence making it easier and easier for people to do countless tasks without getting up, it’s no surprise Americans are becoming increasingly sedentary. The average older adult spends over 9 hours sitting daily, according to previous research mentioned in the study. And that was before the pandemic pushed many people toward even less active lifestyles.
For anyone worried about brain health, the message is clear: cutting sitting time matters just as much as increasing exercise. Standing desks, movement breaks throughout the day, and finding ways to add more motion to daily routines could help protect against cognitive decline.
The evidence points to an important conclusion: what you do between workouts matters just as much as the workouts themselves. Your brain health depends not just on making time for exercise, but on minimizing time spent sitting still.
Paper Summary
Methodology
Researchers from the Vanderbilt Memory and Aging Project studied 404 older adults (71 ± 9 years old) without dementia at baseline. Participants wore a triaxial accelerometer (ActiGraph GT9X Link) on their non-dominant wrist continuously for 7 days to measure sedentary behavior and physical activity levels. They also underwent comprehensive neuropsychological testing and 3T brain MRI scans at baseline and follow-up visits over a 7-year period (average follow-up time was 4.7 years). The researchers used linear regressions for cross-sectional analyses and linear mixed-effects regression models for longitudinal analyses, adjusting for age, sex, race/ethnicity, education, APOE-ε4 status, Framingham Stroke Risk Profile, cognitive status, and intracranial volume (for MRI outcomes). Models were repeated with adjustment for moderate-to-vigorous physical activity to assess the independent contribution of sedentary behavior.
Results
Greater sedentary time was cross-sectionally associated with a smaller Alzheimer’s disease neuroimaging signature (a composite measure of cortical thickness in regions affected by AD) and worse episodic memory performance. Longitudinally, greater sedentary time was associated with faster hippocampal volume reductions and faster declines in naming and processing speed. Many of the observed associations (particularly cross-sectional ones) were stronger in APOE-ε4 carriers, suggesting that genetic risk for Alzheimer’s disease may amplify the negative effects of sedentary behavior. Importantly, most participants (87%) met CDC physical activity guidelines of at least 150 minutes of moderate-to-vigorous activity weekly, suggesting that high physical activity levels do not completely counteract the negative effects of sedentary behavior.
Limitations
The study sample lacked racial and ethnic diversity (85% non-Hispanic White) and was highly educated (average 16 years of education), limiting generalizability. The sample was also quite physically active, with 87% meeting CDC physical activity recommendations, which may limit generalizability to less active populations. The researchers used cross-sectional MRI registration at each time point versus longitudinal registration. The study did not examine the pattern of sedentary behavior (e.g., prolonged sitting versus frequent breaks) or consider a compositional analysis of the 24-hour activity period.
Funding and Disclosures
The research was supported by multiple grants, including T32-AG058524, Alzheimer’s Association IIRG-08-88733, R01-AG034962, K24-AG046373, K01-AG083223, Vanderbilt Clinical Translational Science Awards, Vanderbilt’s High-Performance Computer Cluster for Biomedical Research, and the Richard Eugene Hickman Alzheimer’s Disease Research Endowment. One author, T.J. Hohman, disclosed serving on the Scientific Advisory Board for Vivid Genomics and editorial roles for Alzheimer’s & Dementia journals.
Publication Information
The paper “Increased sedentary behavior is associated with neurodegeneration and worse cognition in older adults over a 7-year period despite high levels of physical activity” was published in the journal Alzheimer’s & Dementia on May 13, 2025. The DOI is 10.1002/alz.70157. The study was led by Marissa A. Gogniat, with senior author Angela L. Jefferson from Vanderbilt Memory and Alzheimer’s Center.