Apolipoprotein E Gene Polymorphisms and Risk of Cognitive Impairment in Polycystic Ovary Syndrome
Objective: To explore the relationship between APOE gene polymorphisms and cognitive function in women with polycystic ovary syndrome (PCOS), and to evaluate whether insulin resistance modifies genetic susceptibility to cognitive impairment.
Methods and Materials: In this cross-sectional study, 120 reproductive-age women with PCOS were evaluated for cognitive performance using the Montreal Cognitive Assessment (MoCA). Hormonal and metabolic parameters were assessed, including total/free testosterone, insulin, HOMA-IR, and HbA1c. APOE polymorphisms (ε2, ε3, ε4 alleles) were genotyped via Sanger sequencing. Logistic regression models were employed to determine the associations between APOE genotypes and cognitive impairment, adjusting for age, education, and metabolic factors.
Findings: Cognitively impaired women exhibited significantly higher free testosterone (p<0.001) and HOMA-IR levels (p=0.012). APOE ε2ε3 and ε3ε4 genotypes were significantly overrepresented in impaired individuals compared to ε3ε3 carriers. Adjusted odds ratios revealed that ε2ε3 carriers had a 4.12-fold higher risk of cognitive impairment (95% CI: 1.21–14.0). A significant APOE × insulin resistance interaction was detected (p=0.048), with ε2ε3 and ε3ε4 carriers showing elevated risk only in the presence of insulin resistance.
Conclusion: APOE polymorphisms are significantly associated with cognitive performance in PCOS, with ε2ε3 and ε3ε4 genotypes conferring higher vulnerability. Insulin resistance may potentiate these genetic effects. APOE genotyping may serve as a tool for cognitive risk stratification in PCOS, pending further validation in larger cohorts.
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