| Title: | Disentangling the effects of sex and gender on APOE ɛ4-related neurocognitive impairment |
| Journal: | Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring |
| Published: | 1 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40352685/ |
| DOI: | https://doi.org/10.1002/dad2.70111 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/dad2.70111 |
Publication 15967
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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.</p>
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.</p>
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 accounting for sex (HR = 1.07, 95% confidence interval: 1.04-1.10, P < 0.0001) with no significant differences by sex or APOE ɛ4 carrier status.</p>
DISCUSSION: Our findings show that APOE ɛ4 increases NCI risk more in females, while FS independently elevates risk across sexes.</p>
Highlights: Apolipoprotein E (APOE) ɛ4 increases neurocognitive impairment (NCI) risk, with a greater impact in females (hazard ratio [HR] = 2.48) than males (HR = 1.96).Sex significantly modifies the effect of APOE ɛ4 on NCI (P < 0.0001f).Femininity score increases NCI risk (HR = 1.07) independently of sex and APOE ɛ4.Understanding the distinct sex and gender contributions to APOE ɛ4-related NCI can improve interventions.</p>
11 Authors
- Tatiana Dessy
- Amina Barhdadi
- Marie-Christyne Cyr
- Johanna Sandoval
- Louis Bherer
- Joëlle Rouleau
- Sylvie Provost
- Louis-Philippe Lemieux Perreault
- Marie-Pierre Sylvestre
- Sarah A. Gagliano Taliun
- Marie-Pierre Dubé
1 Application
| Application ID | Title |
|---|---|
| 20168 | Pharmacogenomic study using the UK Biobank data |
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