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

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, <i>p</i> = 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.