A 24-year ARIC analysis suggests that the setting in which people sit may matter for brain measures linked to vascular health and dementia risk.

Associations of distinct sedentary behaviors with cortical, subcortical, and white matter hyperintensity volumes: Evidence from the ARIC study. Image Credit: Krakenimages.com. Shutterstock

A recent study published in the journal Alzheimer’s \& Dementia found that television watching and occupational sitting were associated with different brain structural measures.

Background

Sedentary behavior (SB) is generally associated with poor health, including Alzheimer’s disease and related dementias (ADRD). Researchers suggest that SB is associated with structural brain differences that are linked to a higher risk of these conditions.

Modifiable behaviors such as increased physical activity and reduced SB are important areas of research as pharmacological treatments for ADRD continue to emerge, while lifestyle strategies remain essential for risk reduction.

Observed structural brain differences include greater white matter hyperintensity (WMH) volume, decreased regional brain volumes, and decreased temporal cortical thickness. WMH is a marker of small vessel disease in the brain and is linked to cognitive impairment and dementia.

However, there is little evidence on specific SB associations with structural brain changes in the “Alzheimer’s disease signature regions.” These are brain regions that could serve as biomarkers for early detection of neurodegeneration, including the parahippocampal gyrus, entorhinal cortex, inferior parietal lobule, hippocampus, cuneus, and precuneus.

Earlier studies have produced conflicting findings, perhaps because they considered SB as a uniform exposure. However, the context of SB matters. The brain impact may differ by type of SB, such as occupational sitting, which may involve greater cognitive engagement, versus lower-cognitive-demand activities such as television viewing.

Cohort Characteristics

To address this gap, the current study examined context-specific SB in association with brain structure over approximately 24 years in a cohort of 1,712 non-demented adults from the Atherosclerosis Risk in Communities (ARIC) study. They focused on specific regions that are affected early in ADRD, besides WMH.

Participants reported their frequency of television watching and occupational sitting over the preceding 12 months at the first study visit in 1987–1989, while brain structure was assessed using 3T magnetic resonance imaging (MRI) approximately 24 years later, in 2011–2013. At this visit, all participants underwent extensive cognitive and neurological testing, after which a subset underwent neuroimaging.

Sedentary Behavior and Brain Regions

Frequent television watching was associated with greater WMH volume and smaller volumes in the frontal and occipital cortices and Alzheimer’s disease-signature regions.

In contrast, participants who always sat during work had lower WMH volume and higher frontal, occipital, and parietal cortical volumes, though the same regions were not consistently affected in both hemispheres or across both sexes. The authors point out that work may involve greater cognitive engagement.

Adjusting for physical activity did not change most associations. The authors suggest that “the context-dependent association between SB and brain structure is at least partially independent of PA and other behavioral and cardiometabolic risk factors.”

Sex-Specific Differences in Sedentary Behavior–Brain Region Associations

These associations were also sex-specific. In women, very frequent television viewing was not associated with any brain region. Always sitting during work was linked to lower volume in the left rostral anterior cingulate cortex, but no other associations were identified. In men, though, moderate and high frequencies of television watching were linked to lower volumes in the frontal, temporal, parietal, occipital, and subcortical deep gray matter, and the Alzheimer’s disease-signature regions. Moderate television watching was also linked to lower occipital and temporal volumes in males.

In contrast, occupational sitting was associated with higher orbitofrontal and occipital cortex volumes as well as other specific regions across both hemispheres. In men, occupational sitting was associated with greater frontal cortical volume.

The overall pattern was broadly consistent after accounting for physical activity and in sensitivity analyses involving the APOE ε4 genotype, in the subset with genotype data, cerebrovascular disease-related mild cognitive impairment, and time-varying covariates, although not every association remained statistically significant across analyses.

Possible Explanations for the Sex-Related Differences

The authors proposed several possible explanations for the sex-specific findings. For instance, males may be more vulnerable to the adverse physiological effects of SB. They also noted that these findings could simply reflect sex-specific patterns of brain aging.

Alternatively, these findings might be due to the more interrupted nature of television watching in women compared to men. This might result in shorter periods of cognitive passivity while watching television with intervals of greater cognitive demand.

Men were also more likely to sit occasionally during work, which was associated with higher cortical volumes. The authors postulate that this might indicate a more cognitively active environment.

In contrast, frequent television watching was also associated with broader structural differences across neural networks. This might potentially reflect not only a low cognitive load but also accumulated vascular risk across multiple neurological circuits.

Frequent television watching was associated with lower thalamic volume, which has been associated with both poor vascular health and cognitive impairment. According to the authors, this could reflect accumulated vascular risk associated with passive SB.

Further analyses, adjusting for cerebrovascular changes associated with mild cognitive impairment, produced mostly consistent findings.

Television Watching and White Matter Hyperintensity Volume

The WMH findings further reinforced context-specific differences: television watching, but not occupational sitting, was associated with greater WMH volume. The authors suggest that this may indicate cumulative vascular risk linked to prolonged SB, possibly due to decreased cerebral blood flow, inflammation, or metabolic impairment.

Unlike prior studies, which yielded conflicting evidence, the current results came from context-specific SB analysis based on prospective follow-up. Based on these findings, they postulate that the association between SB and cerebrovascular disease may be partly independent of physical activity and measured cardiometabolic risk factors.

Relevance of Context-Specific Sedentary Behavior in Dementia Studies

The authors suggest that SB should be interpreted in the context of its cognitive and behavioral factors in studies of brain health, especially among older people who spend more time engaged in sedentary leisure activities. Occasional sitting at work may indicate engagement with cognitively active tasks and may be associated with larger volumes in selected brain regions.

Conversely, prolonged SB may be linked to reduced cerebral blood flow and neural efficiency, even during cognitively demanding sedentary activities. In agreement with this, prior studies indicate that interrupted SB may benefit executive functioning.

Limitations

The study was carried out in a geographically and ethnically diverse cohort in the USA using standardized data to evaluate SB and brain structure. It has several limitations, nonetheless.

It used self-reported SB rather than objective measurements, possibly introducing recall bias. However, the authors also note that, for instance, accelerometry data might not have allowed the granular assessment of SB context, which was vital to this work. The researchers captured perceived SB frequency rather than exact duration, which hindered the identification of cut-offs for each SB category.

Being an observational study, causal inferences could not be made. Finally, SB changes were not captured over time as they were not assessed at the imaging visit. However, analyses that modeled SB reported at visits 1 and 3 as time-varying exposures yielded similar results.

Conclusion

“SB is linked with brain structure and WMH volumes, but its effects vary by behavioral context, for example, television watching versus occupational sitting, and sex.” Future studies and public health strategies should account for context-specific differences in SB when targeting interventions to reduce it.

Sex-specific approaches might also help increase the effectiveness of strategies to support healthy brain aging.