Hearing loss and loneliness in the development of impaired cognition and dementia in the US All of Us cohort: prospective analyses using electronic health records

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Introduction: Hearing loss (HL) and loneliness are independently associated with 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. Methods: Using the National Institutes of Health All of Us Controlled Tier V.8 dataset, we fit adjusted Cox proportional hazards models with distinct baselines for HL (first electronic health record (EHR) visit) and loneliness (social determinants of health survey). Loneliness was measured with the UCLA Loneliness Scale-8 (ULS-8) and analysed 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, removed the ≥1 year EHR follow-up requirement, accounted for death as a competing risk and used time-varying HL in Cox models. Covariates included age, sex, race, education, income, smoking and alcohol use. Results: The EHR observation base included 317 108 adults (mean overall follow-up, 11.8 years); 50 849 (16.0%) had EHR-documented HL and 130 266 (41.1%) had a scoreable ULS-8 loneliness measure. We observed 5663 incident dementia and 21 117 incident IC events. HL was associated with higher risk of incident dementia (HR=1.38, p<0.001) and IC (HR=1.67, p<0.001). Loneliness (per 1-point increase in ULS-8 mean) was associated with higher incident dementia (HR=1.41, p=0.004) and IC (HR=1.48, p<0.001) risk. Mediation analyses indicated small indirect effects of HL via loneliness. The proportion mediated was approximately 2.5% for dementia (pm=0.025, p=0.081) and 2.0% for IC (pm=0.020, p<0.001). Subgroup analyses suggested stronger HL-dementia associations among black/African American participants and stronger HL-IC associations among Asian and black/African American participants, while results from sensitivity analyses were largely confirmatory. Conclusions: In 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 most of the observed HL-cognitive outcome association likely operates through pathways other than loneliness. These findings support further evaluation of hearing rehabilitation and social-connection supports as complementary strategies for cognitive health, while suggesting that addressing HL directly may yield broader benefits than targeting loneliness alone.

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