Sex differences in the association between hearing impairment and brain atrophy: findings from the UK Biobank

Abstract

AbstractBackgroundHearing impairment is highly prevalent in older adults and was recently recognized as a modifiable risk factor for dementia. However, it is unknown if risk differs by sex and whether other issues associated with hearing, like social engagement or depression, impact these associations.MethodUK Biobank data was used to identify 165,471 participants (57±8 years, 55% female) without dementia who had a hearing assessment at baseline. Hearing was assessed using a speech reception threshold task, with scores grouped into good, insufficient, and poor severity levels based on previously derived cut‐offs (Dawes et al., 2014). Cox proportional‐hazard models were used to investigate sex differences in the association between hearing impairment and dementia risk. Sensitivity analyses were conducted to determine if social engagement or depressive symptoms mediated these associations. In a subset of participants with MRI data (n=2,322, 62±7 years, 52% female), linear mixed models stratified by sex were conducted to examine if development of impaired hearing from baseline was associated with gray matter atrophy in auditory and limbic regions.ResultInsufficient and poor hearing were associated with increased risk for dementia compared to good hearing (HR=1.76, 95%CI 1.43‐2.18 and HR=2.13, 95%CI 1.46‐3.11, respectively), but differed by sex. Women with insufficient (HR=1.73, 95% CI 1.25‐2.40) and poor (HR=3.08, 95%CI 1.80‐5.28) hearing had the greatest risk of dementia, whereas only men with insufficient hearing had increased risk (HR=1.78, 95%CI 1.34‐2.35; poor HR=1.60 95%CI 0.94‐2.73). These relationships were not mediated by social engagement or depression. In the MRI subset, women who developed or maintained impaired hearing had greater atrophy over 2.29 years in auditory pathway (e.g., primary auditory cortex, thalamus) and limbic (e.g., hippocampus, parahippocampus, amygdala) regions compared to women with good hearing. Men who developed impairment exhibited decreases over 2.30 years in a secondary auditory region only.ConclusionWomen with impaired hearing have greater risk of dementia compared to men. These sex differences are not mediated by social engagement or depression. Women with impaired hearing exhibit greater atrophy in auditory and limbic regions, while men do not. Sex differences in gray matter atrophy may explain why women with impaired hearing are at greater risk of dementia.