Increase in skeletal muscular adiposity and cognitive decline in a biracial cohort of older men and women

Abstract

Background: Obesity and loss of muscle mass are emerging as risk factors for dementia, but the role of adiposity infiltrating skeletal muscles is less clear. Skeletal muscle adiposity increases with older age and especially among Black women, a segment of the US population who is also at higher risk for dementia.

Methods: In 1634 adults (69-79 years, 48% women, 35% Black), we obtained thigh intermuscular adipose tissue (IMAT) via computerized tomography at Years 1 and 6, and mini-mental state exam (3MS) at Years 1, 3, 5, 8 and 10. Linear mixed effects models tested the hypothesis that increased IMAT (Year 1-6) would be associated with 3MS decline (Year 5-10). Models were adjusted for traditional dementia risk factors at Year 1 (3MS, education, APOe4 allele, diabetes, hypertension, and physical activity), with interactions between IMAT change by race or sex. To assess the influence of other muscle and adiposity characteristics, 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). Models were also adjusted for cytokines related to adiposity: leptin, adiponectin, and interleukin-6.

Results: Thigh IMAT increased by 4.85 cm² (Year 1-6) and 3MS declined by 3.20 points (Year 6-10). The association of IMAT increase with 3MS decline was statistically significant: an IMAT increase of 4.85 cm² corresponded to a 3MS decline of an additional 3.60 points (p < 0.0001), indicating a clinically important change. Interactions by race and sex were not significant.

Conclusions: Clinicians should be aware that regional adiposity accumulating in the skeletal muscle may be an important, novel risk factor for cognitive decline in Black and White participants independent of changes to muscle strength, body composition and traditional dementia risk factors.

Keywords: Black; cognitive decline; dementia; intermuscular adiposity.

Figure 1. CT scans of the mid thigh of two study participants.

Computer Tomography (CT) scans of the mid thigh of 2 study participants showing intermuscular fat (purple), and subcutaneous fat (darker grey) and muscle parenchyma (lighter gray). Note that, albeit similar in cross-sectional thigh muscle area, adiposity is lower in panel A and higher in panel B.

Figure 2:. Minimental score (3MS) by increase in thigh IMAT

Means (standard errors) of Minimental score (3MS) in study year 1 to 10, plotted separately for those with (red) and those without (black) increase in thigh intermuscular adipose tissue (IMAT) from study year 1 to 6 (red: IMAT change > 0; black: IMAT change ≤0). Arrows indicate the two timepoints of IMAT measurements.