Related Experiment Video
Updated: Dec 12, 2025
Cryosectioning and Immunostaining Mouse Inner Ear Tissue: From Embryonic to Adult Stages
Published on: April 11, 2025
Clinician-judged hearing impairment and associations with neuropathologic burden
Willa D Brenowitz1, Lilah M Besser2, Walter A Kukull2
1From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.) and Neurology (K.Y.), Weill Institute for Neurosciences, and Department of Epidemiology & Biostatistics (M.M.G., K.Y.), University of California, San Francisco; Florida Atlantic University (L.M.B.), Institute for Human Health and Disease Intervention, School of Urban and Regional Planning, Boca Raton; National Alzheimer's Coordinating Center (W.A.K.), Department of Epidemiology, and Department of Pathology (C.D.K.), University of Washington, Seattle; and San Francisco VA Health Care System (K.Y.), CA. willa.brenowitz@ucsf.edu.
Objective:
To examine whether neuropathologic burden is associated with hearing impairment.
Methods:
We studied 2,755 autopsied participants ≥55 years of age from the National Alzheimer's Coordinating Center database. Participants had at least 1 clinical evaluation at US National Institute on Aging-funded Alzheimer's Disease Center no more than 2 years before death. Patients were classified as hearing impaired by clinician report at baseline. Common dementia neuropathologies included Alzheimer disease pathologic change (Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque density, neurofibrillary degeneration Braak stage), Lewy body disease, gross infarcts, and microinfarcts. Logistic regression models predicted impaired hearing with adjustment for age at death, sex, race, education, center, and follow-up time. Relative risks were calculated with the use of marginal standardization.
Results:
Impaired hearing was common (32%). In participants who were cognitively normal at baseline (n = 580), impaired hearing was associated with higher Braak stage (relative risk [RR] 1.33 per 2-stage increase, 95% confidence interval [CI] 1.06-1.66) but not other pathologies. In participants with dementia (n = 2,175), impaired hearing was positively associated with microinfarcts (RR 1.18, 95% CI 1.00-1.39) and inversely associated with neuritic plaque density (RR 0.91 per score increase, 95% CI 0.85-0.99). Development of impaired hearing in those with cognitive impairment was associated with neocortical Lewy bodies (1.26, 95% CI 1.02-1.55).
Conclusions:
Impaired hearing, reported before the onset of cognitive impairment, was associated with increased neurofibrillary tangle burden. Impaired hearing in those with cognitive impairment was associated with microinfarcts and neocortical Lewy bodies but not typical Alzheimer disease pathologic change. Functional hearing problems may be a preclinical marker of neurofibrillary neurodegeneration, although replication is needed.
