Hearing loss, plasma neurodegenerative biomarkers, and cognitive function: Independent and additive effects

Background Hearing loss is one of the most prominent modifiable risk factors for dementia, accounting for one of the largest population-attributable risk among midlife exposures according to the Lancet Commission on Dementia. Plasma biomarkers such as neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau-217 (Ptau 217 ) have emerged as promising indicators of neurodegeneration and Alzheimer's disease (AD) pathology. Objective To evaluate whether hearing loss and plasma biomarker concentrations are independently associated with cognitive function in aging adults, and to examine if these associations vary by age group. Methods This cross-sectional study used data from 373 participants in the Aging Adult Brain Connectome (AABC) study. Hearing was assessed using the NIH Toolbox Words-in-Noise test, and cognitive function was measured by a Preclinical Alzheimer's Cognitive Composite (PACC). Plasma biomarkers included NfL, GFAP, total tau (tTau), and Ptau 217 . General linear models tested associations with cognition, adjusting for demographic, genetic, and cardiometabolic covariates. Interaction terms assessed modification by age and hearing. Results Hearing loss was independently associated with lower PACC scores (β = −0.03, p < 0.001), after adjusting for covariates. Higher levels of NfL, GFAP, and Ptau 217 were each associated with worse cognition. Age significantly moderated these associations, with stronger biomarker–cognition links observed in adults aged 65 and older. No significant interactions were observed between hearing loss and plasma biomarkers. Conclusions Hearing loss and plasma biomarkers reflect distinct, additive pathways of cognitive decline. These findings support integrated dementia risk models and highlight the potential of age- and biomarker-informed cognitive monitoring.