Hearing Loss and Loneliness in the Development of Impaired Cognition and Dementia in the All of Us Cohort: Prospective Analyses Using Electronic Health Records

BackgroundHearing loss (HL) and loneliness have each been linked to cognitive decline, yet the extent to which loneliness mediates the HL-cognition relationship remains uncertain. We examined prospective associations among HL, loneliness, and incident dementia and impaired cognition (IC), and tested whether loneliness partially mediates the effect of HL on these outcomes. MethodsUsing the NIH All of Us (AoU) Controlled Tier v8 dataset, we fit adjusted Cox proportional hazards models with distinct baselines for HL (first EHR visit) and loneliness (social determinants of health survey). Loneliness was measured with the UCLA Loneliness Scale-8 (ULS-8) and analyzed as the ULS-8 mean. We conducted four-way decomposition mediation analyses to partition total, direct, and indirect effects, allowing for exposure-mediator interaction. Outcomes (incident dementia and IC) were ascertained from EHRs after the relevant baseline exposure. Sensitivity analyses examined associations in racial/ethnic subgroups, and used time-varying HL in Cox models. Covariates included age, sex, race, education, income, smoking, and alcohol use. FindingsThe analytic sample comprised 317,020 adults (mean overall follow-up, 11.8 years); 50,807 (16.0%) had EHR-documented HL and 132,424 (41.8%) completed the loneliness survey. We observed 6,042 incident dementia and 21,699 incident IC events. HL was associated with higher risk of incident dementia (HR = 1.29, p < .001) and IC (HR = 1.65, p < .001). Loneliness (per 1-point increase in ULS-8 mean) was associated with higher incident dementia (HR = 1.41, 95% CI 1.12-1.75, p = .003) and IC (HR = 1.49, 95% CI 1.36-1.62, p < .001) risk. Mediation analyses indicated small indirect effects of HL via loneliness. The proportion mediated was approximately 2.4% for dementia (pm = 0.024, p = .090) and 2.0% for IC (pm = 0.020, p = .0004). Subgroup analyses suggested stronger HL-dementia associations among Black participants and stronger HL-IC associations among Asian and Black participants, while results from time-varying models were largely confirmatory. InterpretationIn this large, diverse cohort, HL and loneliness were independently associated with incident dementia and IC. Loneliness mediated only a small fraction of the HL effect, suggesting that hearing rehabilitation and social connection supports may be complementary strategies for cognitive health, with potentially more benefits from addressing HL directly. FundingThis study was supported in part by an AoU University of Arizona-Banner Health Driver Grant Program award to Drs. Klimentidis and Sbarra, which was funded in part by the National Institutes of Health Office of the Director through the University of Arizona-Banner AoU Researchers Collective (award OT2OD036485). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AoU Research Program, the National Institutes of Health, or any other funder. The funders had no role in the study design, data access, data analysis and interpretation, the decision to submit the work for publication, or the preparation of the manuscript.