Cholesterol-lowering drug targets reduce risk of dementia: Mendelian randomization and meta-analyses of 1 million individuals.

ABSTRACT:

Introduction

We tested whether genetically proxied non-high-density lipoprotein cholesterol (non-HDL-C)-lowering drug targets reduce risk of all-cause dementia.

Methods

We included 1,091,775 individuals from three prospective general population cohorts with individual-level data and two consortia with summary-level data. We selected genetic variants within HMGCR, NPC1L1, PCSK9, ANGPTL4, LPL, and CETP associated with non-HDL-C. These variants were used as exposures in Cox regression and one- and two-sample Mendelian randomization. Results were meta-analyzed.

Results

Meta-analysis of one-sample Mendelian randomization odds ratios per 1 mmol/L (39 mg/dL) lower non-HDL-C was 0.24 (0.18-0.31) for HMGCR, 0.18 (0.12-0.25) for NPC1L1, 0.97 (0.70-1.35) for PCSK9, 1.66 (0.52-5.

SUBMITTER: Nordestgaard LT 

PROVIDER: S-EPMC12505197 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature