Association Between Cognitive Impairment and Dysphagia: A Two-Sample Mendelian Randomization Study

Abstract

Introduction: Previous observational studies have implied a correlation between cognitive impairment and dysphagia, but some have indicated no correlation between the two. Such contradictory findings may have been influenced by small sample sizes and potential confounders. In this Mendelian randomization (MR) analysis, we genetically estimated a causal relationship between cognitive impairment and dysphagia. Methods: The study included a large meta-analysis of genome-wide association studies (GWAS) of cognitive impairment in 269,867 individuals of European ancestry and pooled data from a GWAS of dysphagia in 165,765 individuals of European ancestry (cases 3497, controls 161,968). We then used five different complementary MR methods, including IVW, MR-Egger, MR-RAPS, weighted median, and weighted mean, to estimate causality between cognitive impairment and dysphagia and finally also assessed heterogeneity and horizontal pleiotropy by extensive sensitivity tests. Results: No evidence of heterogeneity in the effect of instrumental variables was found in Cochran's Q test; therefore, a fixed effects model was used. IVW analysis (OR: 1.206, 95% CI: [1.041, 1.371], p = 0.00508) found that cognitive impairment was associated with an increased risk of dysphagia and that there was a causal association between the two. Also, the weighted median (OR: 1.248, 95% CI: [1.012, 1.484], p = 0.0253), weighted mode (OR: 1.216, 95% CI: [1.043, 1.389], p = 0.0412), and MR-RAPS (OR: 1.225, 95% CI: [1.069, 1.381], p = 0.00627) validated the conclusions. Furthermore, extensive sensitivity analyses found no evidence of heterogeneity or horizontal pleiotropy, confirming the reliability of this MR result. Conclusion: Our MR study demonstrated a causal effect of cognitive impairment on dysphagia from a genetic perspective, suggesting that individuals with a history of cognitive impairment require specific clinical attention to prevent the development of dysphagia.