Sex Differences In The Association Between The Apoe Epsilon 4 Allele And Hearing Impairment: A Longitudinal Memory Clinic Study

Background: The APOE epsilon 4 allele and hearing impairment are risk factors for dementia. Cross-sectional studies have shown controversial findings regarding the relationship between APOE epsilon 4 and hearing impairment. These may be explained by reported sex differences in the association between APOE epsilon 4 and some Alzheimer's disease biomarkers. We aimed to investigate APOE epsilon 4 and hearing impairment in a longitudinal setting considering the modifying effects of sex on APOE epsilon 4.Methods: In total, 1810 subjects with APOE genotype at Ilsan Hospital memory clinics were linked to the longitudinal National Health Insurance Service database with International Statistical Classification of Diseases and Related Health Problems 10th revision (ICD-10) diagnosis codes of hearing impairment. After excluding cases with prevalent hearing impairment and incomplete records, 1092 subjects were analyzed for the period January 2004-July 2019. We used Cox proportional hazard models with or without adjustment for education, hypertension, diabetes, and cognitive function. Effect modification was analyzed by sex stratification and by adding APOE epsilon 4 by sex interaction terms.Results: Hearing impairment did not differ between APOE epsilon 4 carriers and non-carriers. Sex-stratification analysis with an unadjusted model showed men with APOE epsilon 4 developed more hearing impairment than men without (HR 1.90, 95% CI 1.20-3.01), but women did not. The results remained similar in covariate-adjusted models. The interaction between APOE epsilon 4 and sex was also significant regardless of adjustment.Conclusions: Our longitudinal analyses suggested male memory clinic visitors with APOE epsilon 4 allele were more likely to develop hearing impairment than those without the genotype. This group may benefit more from regular monitoring and preventive measures for hearing impairment.