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

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Keywords: Brain atrophy; CSF tau protein; Cognitive decline; Hearing impairment.

Fig. 1

The association of hearing performance with cognitive function. a. The association of hearing performance with fluid intelligence, numeric memory, reaction time and pairs matching in the cross-sectional study; b. The association of hearing performance with fluid intelligence, numeric memory, reaction time and pairs matching in the longitudinal study. The association of hearing performance with cognitive function were investigated using the multiple linear regression models with the covariates regressed out including age, sex, body mass index, Townsend deprivation index, education qualification, smoking status, and drinking status in the UK Biobank. All P values were calculated after Bonferroni correction. Abbreviations: SiN, Speech in Noise.

Fig. 2

The association of polygenic risk score for hearing performance with cognitive function and brain structure. The polygenic risk score (PRS) for hearing performance was associated with cognitive function, grey matter volume, and white matter microstructure integrity in the multiple linear regression models with the covariates including age, sex, body mass index, Townsend deprivation index, education qualification, smoking status, drinking status, and imaging scanning sites (only for brain imaging) in the UK Biobank. Abbreviations: PRS, polygenic risk scores; “∗” P < 0.05; “∗∗” P < 0.01; “∗∗∗” P < 0.005; “∗∗∗∗” P < 0.001.

Fig. 3

The association of hearing performance with brain structure. a. Lower volume of cortical and subcortical regions was associated with poor hearing performance; b. Higher mean diffusivity of white matter tracts was associated with poor hearing performance. The hearing performance was measured using the speech-in-noise test, in which the higher speech-reception-threshold indicated the poorer hearing performance. The association between hearing performance and brain structure were investigated in the multiple linear regression models with the covariates regressed out including age, sex, body mass index, Townsend deprivation index, education qualification, smoking status, drinking status, and imaging scanning sites in the UK Biobank.

Fig. 4

The association of hearing performance with CSF proteins. Higher level of CSF t-tau and p-tau were associated with poor hearing performance. The SMD (Standard Mean Difference) and 95% CI were from the meta-analysis with random-effects. Abbreviations: CSF, cerebrospinal fluid; CABLE, Chinese Alzheimer's Biomarker and Lifestyle; ADNI, Alzheimer's Disease Neuroimaging Initiative; SD, Standard Deviation; SMD, Standard Mean Difference; CI, Confidence Interval.

Fig. 5

Mediation analysis of the association between hearing performance and cognitive function. a. Mediation analysis: the mediation implemented by brain regions from hearing performance on cognitive function was significant (β = −0.006, P = 2.4 × 10⁻¹⁴, 95%CI: −0.008 to −0.005); b. Mediation analysis: the mediation implemented by fractional anisotropy of white matter tracts from hearing performance on cognitive function was significant (β = −0.002, P = 2.6 × 10⁻⁸, 95%CI: −0.003 to −0.002); c. Mediation analysis: the mediation implemented by mean diffusivity of white matter tracts from hearing performance on cognitive function was significant (β = −0.001, P = 6.9 × 10⁻⁴,95%CI: −0.001 to −0.0003); d. Mediation analysis: the mediation implemented by CSF tau protein from hearing performance on cognitive function (β = −0.020, P = 3.5 × 10⁻², 95%CI: −0.039 to −0.001). e. Mediation analysis: the mediation implemented by the volume of brain regions from the PRS for hearing performance on cognitive function (β = −0.007, P = 1.1 × 10⁻¹², 95%CI: −0.009 to −0.005). f. Mediation analysis: the mediation implemented by the FA of white matter tracts from the PRS for hearing performance on cognitive function (β = −0.002, P = 1.7 × 10⁻⁴, 95%CI: −0.003 to −0.001). The indirect and direct effects and P values were estimated using nonparametric bootstrapping with 10,000 iterations with the “Lavaan” package in R software, version 4.2.0. Abbreviations: SiN, Speech in Noise; CSF, Cerebrospinal Fluid; MoCA, Montreal Cognitive Assessment; CI, Confidence Interval; FA, Fractional anisotropy; MD, Mean diffusivity; PRS, polygenic risk score.