Causal relationship between proton pump inhibitors and dementia risk: evidence from a Mendelian randomization study

This study aims to analyze the causal relationship between Proton Pump Inhibitors (PPI) and the risk of Dementia (DEM) using Mendelian Randomization (MR) analysis, providing a reference for clinical medication decisions.

Based on summary data from Genome-Wide Association Studies (GWAS), this study uses two common PPI drugs, Lansoprazole (LAN) and Omeprazole (OME), as exposure factors. DEM and its five subtypes: Dementia in Alzheimer Disease (DAD), Vascular Dementia (VD), Dementia due to Parkinson Disease (DPD), Dementia with Lewy bodies (DLB), and Frontotemporal Dementia (FTD) are used as outcome factors. The main method used to assess causal relationships is the Inverse Variance Weighted (IVW) method; other MR methods and sensitivity analyses are also conducted as supplements.

There is a significant positive causal relationship between LAN and DEM (IVW: OR = 1.29E + 05, 95% CI: 1.60E + 00 to 1.04E + 10; P = 0.041), and DAD (IVW: OR = 2.39E + 04, 95% CI: 1.09E + 00 to 5.23E + 08; P = 0.048); no significant causal relationship was found between LAN and VD, DPD, DLB, FTD (P > 0.05). There is a significant positive causal relationship between OME and FTD (IVW: OR = 2.95E + 11, 95% CI: 2.13E + 02 to 4.09E + 20; P = 0.014), and a significant negative causal relationship with VD (IVW: OR = 9.56E-07, 95% CI: 1.69E-12 to 5.40E-01; P = 0.040); no significant causal relationship was found between OME and DEM, DAD, DPD, DLB (P > 0.05).

This study reveals that LAN may increase the risk of DEM and DAD; OME may increase the risk of FTD and may reduce the risk of VD. This provides a reference for the rational clinical use of PPI.