The association between sarcopenia, sedentary behavior, and the motor cognitive risk syndrome: A Mendelian randomization study

Recent observational studies have suggested a potential association between sarcopenia and motor cognitive risk syndrome (MCR), but the underlying mechanism of action has not been elucidated, and perhaps sedentary behavior may play a key role in the association. To further investigate this association, this study utilized publicly available genome-wide association study data. First, a bidirectional Mendelian randomization (MR) approach was employed to examine the relationship between sarcopenia-related phenotypes (including appendicular lean mass [ALM] [N = 450,243], handgrip strength [HGS] [N = 256,523], and walking pace [WP] [N = 459,915]) with MCR (N = 22,593). Subsequently, a two-step MR approach was employed to investigate whether sedentary behavior (nonwork computer use) (N = 422,218) mediates this causal association. Positive MR results showed that all relevant phenotypes of sarcopenia had a significant positive correlation with cognitive function, including ALM (odds ratios [OR] = 1.10, 95% confidence intervals [CIs]: 1.04-1.15; P < .01), left HGS (OR = 1.22, 95% CI: 1.02-1.47; P = .02), right HGS (OR = 1.22, 95% CI: 1.01-1.47; P = .03), and WP (OR = 3.06, 95% CI: 1.99-4.71; P < .01). The results of the reverse MR analysis indicate that cognitive function is positively associated only with WP (OR = 1.02, 95% CI: 1.00-1.04; P = .01), while there was no significant correlation with ALM, left, and right HGS. Mediation analysis further revealed that recreational computer use partially mediated the associations between ALM, HGS, and WP and cognitive function. The results of this study suggest that declines in ALM, HGS, and WP significantly increase the risk of developing MCR. Meanwhile, the onset of MCR may further compromise gait speed, potentially creating a vicious cycle. In addition, recreational computer use has an important mediating role in the association between sarcopenia and MCR. In patients with sarcopenia, excessive recreational computer use appears to accelerate cognitive impairment, potentially aggravating the risk of developing MCR. Future recommendations suggest that middle-aged and older adults, particularly those with sarcopenia, should appropriately reduce sedentary behavior. Such interventions can serve as early strategies to prevent cognitive decline, thereby enhancing overall quality of life.