Abstract
BACKGROUND: The burgeoning recognition of the nexus between renal functionality and the prevalence of dementia has precipitated a surge in research endeavors. This study aims to substantiate the causal relationship between kidney functionality and dementia. METHODS: We utilized clinical renal function metrics from the Chronic Kidney Disease Genetics (CKDGen) Consortium and diverse dementia types (Alzheimer's disease [AD] and vascular dementia) from the FinnGen Biobank by using Mendelian randomization analysis. At the stratum of genetic susceptibility, we tested the causal relationship between variations index in renal function and the occurrence of dementia. Inverse-variance weighted (IVW) method was the main analysis, and several supplementary analyses and sensitivity analyses were performed to test the causal estimates. RESULTS: The findings indicate a significant correlation between each unit increase in cystatin C-based estimated glomerular filtration rate (eGFR-cys) levels was significantly associated with a reduction in the incidence of late-onset Alzheimer's disease (LOAD) (IVW: OR = 0.35, 95% CI: 0.13-0.91, p = 0.031). After adjusting for creatinine-based eGFR (eGFR-cre) and urinary albumin-to-creatinine ratio (UACR), a causal relationship was still identified between elevated levels of eGFR-cys and decreased risk of LOAD (IVW: OR: 0.08; 95% CI: 0.01-0.97, p = 0.047). Sensitivity tests demonstrated the reliability of causal estimates. CONCLUSIONS: The association between renal function based on cystatin C and the augmented risk of developing AD lends support to the perspective that regular monitoring of cystatin C may be a valuable investigative biomarker.