Sex differences in the association between the APOEε4 allele and hearing impairment: A longitudinal memory clinic study

•Both APOEε4 and hearing impairment (HI) are strong risk factors for dementia.•The relationship between the APOEε4 and HI has been controversial.•The modifying effects of sex on the APOEε4 may have contributed to the mixed results.•In our longitudinal setting, male memory clinic visitors with APOEε4 had a higher risk for HI.•Some effects of APOEε4 on dementia may be mediated by HI. The APOEε4 allele and hearing impairment are risk factors for dementia. Cross-sectional studies have shown controversial findings regarding the relationship between APOEε4 and hearing impairment. These may be explained by reported sex differences in the association between APOEε4 and some Alzheimer's disease biomarkers. We aimed to investigate APOEε4 and hearing impairment in a longitudinal setting considering the modifying effects of sex on APOEε4. 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 APOEε4 by sex interaction terms. Hearing impairment did not differ between APOEε4 carriers and non-carriers. Sex-stratification analysis with an unadjusted model showed men with APOEε4 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 APOEε4 and sex was also significant regardless of adjustment. Our longitudinal analyses suggested male memory clinic visitors with APOEε4 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.