Disentangling the effects of sex and gender on <i>APOE</i> ɛ4-related neurocognitive impairment.

ABSTRACT:

Introduction

The apolipoprotein E (APOE) ɛ4 allele is a well-established risk factor for neurocognitive impairment (NCI), with varying impacts between men and women. This study investigates the distinct roles of sex and gender in modifying APOE ɛ4-related NCI.

Methods

Biological sex was inferred from sex chromosomes, and a femininity score (FS) was used as a proxy for gender. We analyzed 276,596 UK Biobank participants without prior NCI to assess whether sex and FS modified the effect of APOE ɛ4 on NCI.

Results

NCI risk was higher in APOE ɛ4 carriers compared to non-carriers (hazard ratio [HR] = 2.48 in females; HR = 1.96 in males) with significant interaction by sex (P < 0.0001). FS was associated with an increased NCI risk after ac

SUBMITTER: Dessy T 

PROVIDER: S-EPMC12064333 | biostudies-literature | 2025 Apr-Jun

REPOSITORIES: biostudies-literature