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

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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.

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