Could Skeletal Muscle Adiposity Be a Risk Factor for Cognitive Decline?

Regional adiposity accumulating in the skeletal muscle may be an important, novel risk factor for cognitive decline, according to study findings published in the Journal of the American Geriatrics Society.

Obesity and loss of muscle mass are emerging risk factors for dementia, especially for Black women who are at higher risk for dementia. Moreover, skeletal muscle adiposity increases with older age. For the study, researchers investigated the role of adiposity infiltrating skeletal muscles.

The researchers assessed adiposity and cognitive function of 1,634 adult participants (mean age, 73.38 years at baseline; 48% women; 35% Black) for a 10-year period. Via computerized tomography, they obtained thigh intermuscular adipose tissue (IMAT) at years 1 and 6, and a mini-mental state exam (3MS) at years 1, 3, 5, 8, and 10. They tested the hypothesis that increased IMAT (year 1–6) and would be associated with 3MS decline (year 5–10), using linear mixed effects models. With interactions between IMAT change by race or sex, models were adjusted for traditional dementia risk factors at year 1.

Models accounted for change in muscle strength, muscle area, body weight, abdominal subcutaneous and visceral adiposity, and total body fat mass (all measured in years 1 and 6) to assess the influence of other muscle and adiposity characteristics. The researchers also adjusted the models for cytokines related to adiposity: leptin, adiponectin, and interleukin-6.

The study findings revealed an increase in thigh IMAT by 4.85 cm² (year 1–6) and 3MS declined by 3.20 points (year 6–10). Moreover, there was a statistically significant association of IMAT increase with 3MS decline, shown by an IMAT increase of 4.85 cm² corresponding to a 3MS decline of an additional 3.60 points (P <.0001). No statistical significance was identified for interactions by race and sex (P >.08).

The researchers explained that, independent of traditional risk factors for dementia and other body composition depots, the study identified increasing skeletal muscle adiposity as a predictor of declining cognitive function. Moreover, they noted that prediction models of dementia risk may be improved by these findings and those of future studies of muscle adiposity.

“Our results suggest that muscle adiposity may have a valuable role as a predictor of cognitive decline in addition to (not instead of) other traditional dementia risk factors, with applicability in clinical settings,” the researchers wrote.

Study limitations included its assessment of cognitive decline using only the 3MS, which does not capture certain domains of cognition. Moreover, the study findings may not be generalizable to other racial and ethnic groups outside of the study population.