Associations of 35 Serum and Urine Biomarkers With Vascular Dementia—A Mendelian Randomization Study

Background: The relationship between serum and urine biomarkers with vascular dementia (VD) has been increasingly highlighted by observational studies. Yet, the causal nature underlying these associations remains elusive.

Objective: This research seeks to elucidate the causal relationships between 35 prevalent serum and urine biomarkers and the risk of VD onset through Mendelian randomization methods.

Methods: This study employs bidirectional Mendelian randomization, incorporating both forward and reverse approaches, to examine these potential causal links. The findings from the Mendelian randomization are further analyzed for pleiotropy, heterogeneity, and sensitivity to ensure robustness.

Results: The analysis through forward Mendelian randomization reveals that elevated levels of aspartate aminotransferase (AST) and triglycerides (TG) are linked to an elevated risk of developing VD, whereas higher levels of direct bilirubin (DBil) appear to mitigate this risk. These outcomes are corroborated by subsequent analyses for pleiotropy, heterogeneity, and sensitivity. On the other hand, reverse Mendelian randomization indicates that VD does not causally influence the levels of the 35 examined serum and urine biomarkers.

Conclusion: The outcomes of this Mendelian randomization study affirm the causal influence of biomarkers AST, TG, and DBil on the progression of VD. These insights pave the way for leveraging AST, TG, and DBil as biochemical indicators for the forecasting, screening, and early diagnosis of VD, offering avenues for targeted interventions and management.