Association of glymphatic system, neurofluidic dysfunction, and peripheral inflammation in age-related hearing loss.

OBJECTIVE: Age-related hearing loss (ARHL) is linked to cognitive decline, but mechanisms remain unclear. This study examined four complementary MRI measures related to glymphatic and neurofluid function in ARHL, together with plasma inflammatory and neurodegeneration-related biomarkers and cognitive assessments. METHODS: Sixty-six ARHL participants and 139 matched controls underwent cognitive testing (MoCA, MMSE, CFT-d), MRI-based glymphatic evaluation (DTI-ALPS, FW-WM, CPV, gBOLD-CSF), and measurement of TNF-α, IL-1β, IL-6, NfL, p-tau181, GFAP, and Aβ40. Correlation and mediation analyses were performed. RESULTS: ARHL participants showed poorer cognition, higher inflammatory cytokines, increased CPV and FW-WM, and reduced ALPS. Worse hearing correlated with higher inflammatory cytokine levels, lower ALPS, and higher FW-WM. Mediation analysis revealed that lower ALPS partly mediated the association between PTA and cognitive decline, with TNF-α and IL-1β further contributing. CPV and FW-WM increased with hearing thresholds, while gBOLD-CSF coupling showed a nonlinear association. CONCLUSION: ARHL was associated with poorer cognitive performance, altered multimodal MRI markers related to glymphatic and neurofluid function, and elevated circulating inflammatory cytokines. These convergent findings identify potential neurofluidic and inflammatory correlates of cognitive impairment in ARHL.