Hearing impairment is associated with cognitive decline, brain atrophy and tau pathology

Hearing impairment was recently identified as the most prominent risk factor for dementia. However, the mechanisms underlying the link between hearing impairment and dementia are still unclear.We investigated the association of hearing performance with cognitive function, brain structure and cerebrospinal fluid (CSF) proteins in cross-sectional, longitudinal, mediation and genetic association analyses across the UK Biobank (N = 165,550), the Chinese Alzheimer's Biomarker and Lifestyle (CABLE, N = 863) study, and the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 1770) database.Poor hearing performance was associated with worse cognitive function in the UK Biobank and in the CABLE study. Hearing impairment was significantly related to lower volume of temporal cortex, hippocampus, inferior parietal lobe, precuneus, etc., and to lower integrity of white matter (WM) tracts. Furthermore, a higher polygenic risk score (PRS) for hearing impairment was strongly associated with lower cognitive function, lower volume of gray matter, and lower integrity of WM tracts. Moreover, hearing impairment was correlated with a high level of CSF tau protein in the CABLE study and in the ADNI database. Finally, mediation analyses showed that brain atrophy and tau pathology partly mediated the association between hearing impairment and cognitive decline.Hearing impairment is associated with cognitive decline, brain atrophy and tau pathology, and hearing impairment may reflect the risk for cognitive decline and dementia as it is related to bran atrophy and tau accumulation in brain. However, it is necessary to assess the mechanism in future animal studies.A full list of funding bodies that supported this study can be found in the Acknowledgements section.