A causal relationship between sarcopenia and cognitive impairment: A Mendelian randomization study.
Study Goal
The researchers aimed to investigate the causal relationship between sarcopenia-related muscle characteristics (including walking pace) and cognitive performance in the elderly.
Results Summary
The study found a significant causal relationship between faster walking pace and improved cognitive function, supported by multiple genetic analyses (LDSC, MR, and MVMR). Walking pace showed consistent positive associations with cognitive performance across different statistical models.
Population
Elderly individuals (specific age range not specified)
Effective Dosage
Not specified
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
appendicular lean mass (ALM) | increase | cognitive function | - | β = 0.049; 95% CI: 0.032-0.066 | causal relationship | #1 |
walking pace | increase | cognitive function | - | β = 0.349; 95% CI: 0.210-0.487 | causal relationship | #2 |
appendicular lean mass (ALM) in males | increase | cognitive function | male | β = 0.060; 95% CI: 0.031-0.089 | causal relationship | #3 |
appendicular lean mass (ALM) in females | increase | cognitive function | female | β = 0.045; 95% CI: 0.020-0.069 | causal relationship | #4 |
low grip strength | no change | cognitive function | - | β = -0.045; 95% CI: -0.092 - -0.002 | not causally associated | #5 |
cognitive function | increase | appendicular lean mass (ALM) | - | β = 0.033; 95% CI: 0.018-0.048 | causal relationship | #6 |
cognitive function | increase | walking pace | - | β = 0.039; 95% CI: 0.033-0.051 | causal relationship | #7 |
cognitive function | increase | appendicular lean mass (ALM) in males | male | β = 0.041; 95% CI: 0.019-0.063 | causal relationship | #8 |
cognitive function | increase | appendicular lean mass (ALM) in females | female | β = 0.034; 95% CI: 0.010-0.058 | causal relationship | #9 |
cognitive function | no change | low grip strength | - | β = -0.024; 95% CI: -0.073-0.025 | not causally related | #10 |
appendicular lean mass (ALM) | increase | cognitive function | - | β = 0.077; 95% CI: 0.044-0.109 | significant causal relationship | #11 |
walking pace | increase | cognitive function | - | β = 0.579; 95% CI: 0.383-0.775 | significant causal relationship | #12 |
appendicular lean mass (ALM) | increase | cognitive function | - | β = 0.069; 95% CI: 0.033-0.106 | causality remained | #13 |
walking pace | increase | cognitive function | - | β = 0.589; 95% CI: 0.372-0.806 | causality remained | #14 |
low appendicular lean mass (ALM) | decrease | reduced cognitive performance | - | - | causally involved in | #15 |
slow walking pace | decrease | reduced cognitive performance | - | - | causally involved in | #16 |
OBJECTIVE: Sarcopenia and cognitive impairment often coexist in the elderly. In this study, we investigated the causal relationship between sarcopenia-related muscle characteristics and cognitive performance. METHODS: We used linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR) analyses to estimate genetic correlations and causal relationships between genetically predicted sarcopenia-related muscle traits and cognitive function, as well as cognitive function-based discovery samples and replicated samples. Estimated effect sizes were derived from a fixed-effects meta-analysis. RESULTS: Our univariate genome-wide association study (GWAS) meta-analysis indicated a causal relationship between appendicular lean mass (ALM) (β = 0.049; 95% confidence interval (CI): 0.032-0.066, P < 0.001) and walking pace (β = 0.349; 95% CI: 0.210-0.487, P < 0.001) with cognitive function, where a causal relationship existed between ALM in both male and female (βALM-Male(M) = 0.060; 95% CI: 0.031-0.089, PALM-M < 0.001; βALM-Female(F) = 0.045; 95% CI: 0.020-0.069, PALM-F < 0.001) with cognitive function. Low grip strength was not causally associated with cognitive function (β = -0.045; 95% CI: -0.092 - -0.002, P = 0.062). A reverse causality GWAS meta-analysis showed a causal relationship between cognitive function and ALM (β = 0.033; 95% CI: 0.018-0.048, P < 0.001) and walking pace (β = 0.039; 95% CI: 0.033-0.051, P < 0.001), where ALM in both male and female showed a causality (βALM-M = 0.041; 95% CI: 0.019-0.063, PALM-M < 0.001; βALM-F = 0.034; 95% CI: 0.010-0.058, PALM-F = 0.005). Cognitive function was not causally related to low grip strength (β = -0.024; 95% CI: -0.073-0.025, P = 0.344). Multivariable MR1 (MVMR1) analyses showed a significant causal relationship for ALM (β = 0.077; 95% CI: 0.044-0.109, P = 0.000) and walking pace (β = 0.579; 95% CI: 0.383-0.775, P = 0.000) and cognitive function. Multivariable MR2 (MVMR2) multivariate analysis showed that ALM causality remained (β = 0.069; 95% CI: 0.033-0.106, P = 0.000), and walking pace (β = 0.589; 95% CI: 0.372-0.806, P = 0.000). CONCLUSIONS: Bidirectional two-sample MR demonstrated that sarcopenia-related muscle characteristics and cognitive performance were positive causal genetic risk factors for each other, while a multivariable MR study demonstrated that low ALM and a slow walking pace were causally involved in reduced cognitive performance. This study suggests a causal relationship between sarcopenia and cognitive impairment in older adults and provide new ideas for prevention and treatment.