Hearing Loss, Brain Structure, Cognition, and Dementia Risk in the Framingham Heart Study.

Importance: Age-related hearing loss is a potentially modifiable risk factor for cognitive impairment and dementia. Objective: To investigate the association of hearing loss with brain structure changes, cognitive function, and incident dementia. Design, Setting, and Participants: This cohort study included Framingham Heart Study Offspring Study participants attending their sixth quadrennial examination (1995-1998) divided into 2 partially overlapping samples. Sample 1 participants underwent brain magnetic resonance imaging and cognitive assessment at their seventh and eighth quadrennial examinations. Sample 2 included participants aged 60 years or older at pure tone average (PTA) analysis and subsequently followed up for incident dementia. The data analysis was performed between January 12, 2024, and August 24, 2025. Exposure: Hearing loss. Main Outcomes and Measures: The main outcomes were changes in brain volume on MRI, cognitive performance on neuropsychological testing, and incident all-cause dementia. Multivariable linear regressions were used to compare PTA and hearing loss categories with neuropsychological measures and total cerebral, hippocampal, and white matter hyperintensity brain volumes. Cox proportional hazards regression was used to examine longitudinal associations between PTA and hearing loss categories and incident dementia. Results: Sample 1 included 1656 participants (mean [range] age, 58.1 [29.7-85.6] years; 903 female [54.5%]), and sample 2 included 935 participants (mean [range] age, 67.6 [60.0-85.6] years; 518 female [55.4%]). Participants with mild or greater hearing loss, compared with those with no or only slight hearing loss, had significantly smaller brain volumes (β [SE], -4.10 [1.76]) and declines in executive function (β [SE], -0.04 [0.01]). Participants with at least slight hearing loss, compared with those with no hearing loss, had significant increases in white matter hyperintensity volume (β [SE], 0.02 [0.01]) and a higher risk of developing all-cause dementia (hazard ratio, 1.71; 95% CI, 1.01-2.90) over 15 years of follow-up, particularly among those with at least 1 apolipoprotein E ε4 allele (hazard ratio, 2.86; 95% CI, 1.12-7.28). Conclusions and Relevance: This cohort study found that midlife hearing loss was associated with smaller brain volumes, accelerated worsening in executive function, and an increased risk of dementia, suggesting that it may be an early marker of brain aging and dementia risk.