Causal association of sarcopenia with brain cortical structure: A Mendelian randomization study

Abstract

Abstract Background Patients with sarcopenia are often accompanied by cognitive decline even affecting cortical structures, however, the causal link has not been explained. We used Mendelian randomization (MR) to explain the relationship between muscle and cortical structure. Methods Genome-wide association studies summary data of appendicular lean mass (ALM) in 450,243 UK Biobank participants were used to identify genetically predicted ALM. Data from 454,633 individuals from UK Biobank were used to assess genetically determined body fat percentage (BFP); 461,089 participants from the UK Biobank were used to evaluate genetically predicted right-hand grip strength (HGS-R); 461,026 participants from the UK Biobank were used to evaluate genetically predicted left-hand grip strength (HGS-L). Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between ALM, BFP, HGS-L, and HGS-R with alterations in cortical thickness (TH) or surficial area (SA) of the brain. We used three different MR methods: inverse-variance weighted (IVW) analysis, MR-Egger regression, and weighted median test. For significant estimates, we further used Cochran’s Q test, MR-Egger intercept test, leave-one-out analyses and MR-PRESSO to assess heterogeneity. Results At the global level, the genetically predicted HGS-R significantly linked to the increase of global SA (β = 5048.6960 mm2, 95% CI: 2123.3746 mm2 to 7974.0174 mm2, P = 0.0007). At the functional region level, ALM was found to significantly decrease the TH of lateral occipital gyrus (β = -0.0079 mm, 95% CI: -0.0117 mm to -0.0041 mm, P = 4.17 × 10− 5) and notably increase the TH of pars opercularis gyrus(β = 0.008 mm, 95% CI: 0.0042 mm to 0.0117 mm, P = 3.12 × 10− 5);BFP significantly raised the TH of the superior parietal gyrus (β = -0.0136 mm, 95% CI: 0.0066 mm to 0.0207 mm, P = 1.61 × 10− 4). Conclusions Our study shows a significant association between sarcopenia and cortical structure, supporting the muscle-brain axis theory. Brain MRI could potentially be utilized for diagnosis of neuropsychiatric disorders in individuals with sarcopenia, and patients with sarcopenia may improve cognition through exercise.