Linking sarcopenia, brain structure, and cognitive performance: a large-scale UK Biobank study

Abstract

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure, and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure, and cognitive performance.

We included 33,709 UK Biobank participants (54.2% female; age range 44 to 82 years) with structural and diffusion MRI, thigh muscle fat infiltration (n=30,561) from whole-body MRI (muscle quality indicator), and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n=22,530). Of these, 1,703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32,006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia vs. non-sarcopenia; and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy, and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders.

We show that sarcopenic traits (probable sarcopenia vs. non-sarcopenia; and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain MRI measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes), and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes [0.02, 0.06] and p-values in [0.0002, 4.2e-29]. In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts), and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes [0.02, 0.07] and p-values in [0.0002, 1.9e-31]. The regions showing the most significant effect sizes across the cortex, white matter, and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits (probable sarcopenia: p-values in [0.0001, 1.0e-11]; muscle fat infiltration: p-values in [7.7e-05, 1.7e-12]).

Our findings show significant associations between sarcopenic traits, brain structure, and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.