# Meta-analysis reveals apolipoprotein ε4 confers higher susceptibility to Parkinson’s disease dementia in Asian populations

## TL;DR

A meta-analysis finds that the APOE ε4 gene variant increases the risk of Parkinson's disease dementia, especially in Asian populations.

## Contribution

This study identifies a stronger association between APOE ε4 and Parkinson’s disease dementia in Asian populations compared to Caucasians.

## Key findings

- APOE ε4 carriers have a 1.52-fold higher risk of Parkinson’s disease dementia compared to ε3/3 carriers.
- Subgroup analysis shows higher susceptibility in Asian populations (OR = 1.98) compared to Caucasians (OR = 1.48).
- ε3/4 and ε4/4 genotypes are linked to increased Parkinson’s disease dementia risk.

## Abstract

Multiple studies show conflicting association between APOE polymorphisms and the risk of PDD, yielding inconsistent results. To elucidate, a meta-analysis was conducted using existing articles from Web of Science, PubMed, Cochrane, Google Scholar, Embase, WanFang, and CNKI databases, including case-control studies published up to January 31, 2025. A total of 27 studies (3,115 PD controls and 1,338 PDD cases) were included, with pooled Odds Ratio (ORs) and 95% confidence intervals (CIs) calculated using CMA, Biostat, United States. To assess APOE genotypes and PDD risk, three comparisons were examined: 5 genotypes vs. ε3/3, ε2+/ε4 + vs. ε3/3, and ε4 + vs. ε4−. The ε3/4 (OR = 1.56, 95% CI: 1.25–1.95); ε4 + vs. ε3/3 (OR = 1.52, 95% CI: 1.20–1.93) and ε4 + vs. ε4− (OR = 1.62, 95% CI: 1.39–1.90) genotypes were associated with an increased PDD risk, while ε2 + showed no significant effect (OR = 1.21, 95% CI: 0.88–1.65, p = 0.23). Carriers of ε4 + had a 1.52-fold higher risk compared to ε3/3, and the ε4 + vs. ε4 − comparison revealed a 1.62-fold greater dementia risk in ε4 + carriers. Subgroup analysis by ancestral region confirmed ε4 + as a significant risk factor for PDD across Asian, and Caucasians populations with higher susceptibility in Asian (OR = 1.98, 95% CI: 1.29–3.05) vs. Caucasian (OR = 1.48, 95% CI: 1.11–1.98) populations. Our findings suggest that ε3/4 and ε4/4 increase susceptibility to PDD, underscoring the need for further large-scale studies to validate these associations.