Association of genetic risk for Alzheimer disease and hearing impairment

Abstract

Objective: To test the hypothesis that incipient Alzheimer disease (AD) may adversely affect hearing and that hearing loss may adversely affect cognition, we evaluated whether genetic variants that increase AD risk also increase problem hearing and genetic variants that increase hearing impairment risk do not influence cognition.

Methods: UK Biobank participants without dementia ≥56 years of age with Caucasian genetic ancestry completed a Digit Triplets Test of speech-in-noise hearing (n = 80,074), self-reported problem hearing and hearing with background noise (n = 244,915), and completed brief cognitive assessments. A genetic risk score for AD (AD-GRS) was calculated as a weighted sum of 23 previously identified AD-related polymorphisms. A genetic risk score for hearing (hearing-GRS) was calculated using 3 previously identified polymorphisms related to hearing impairment. Using age-, sex-, and genetic ancestry-adjusted logistic and linear regression models, we evaluated whether the AD-GRS predicted poor hearing and whether the hearing-GRS predicted worse cognition.

Results: Poor speech-in-noise hearing (>-5.5-dB speech reception threshold; prevalence 14%) was associated with lower cognitive scores (ß = -1.28; 95% confidence interval [CI] -1.54 to -1.03). Higher AD-GRS was significantly associated with poor speech-in-noise hearing (odds ratio [OR] 1.06; 95% CI 1.01-1.11) and self-reported problems hearing with background noise (OR 1.03; 95% CI 1.00-1.05). Hearing-GRS was not significantly associated with cognitive scores (ß = -0.05; 95% CI -0.17 to 0.07).

Conclusions: Genetic risk for AD also influences speech-in-noise hearing. We failed to find evidence that genetic risk for hearing impairment affects cognition. AD disease processes or a that shared etiology may cause speech-in-noise difficulty before dementia onset.

Figure 1. Conceptual models of AD genetic risk, dementia, and hearing loss motivating analysis

Genetic variants known to increase Alzheimer disease (AD) risk can be used to distinguish between mechanisms that may explain the previously documented association between hearing loss and dementia risk. If incipient neurodegeneration or other shared etiologies influence hearing loss, it implies that genetic variants that increase the risk of dementia will also be associated with increased risk of hearing loss (A). If hearing loss has effects on biological or social processes that increase risk of dementia, it implies that genetic risk for AD will be independent of (not associated with) hearing loss (B) but that genetic risk for hearing impairment will be associated with risk of dementia.

Figure 2. Association between speech-in-noise SRT and quartiles of AD-GRS (n = 80,074)

There was a significant trend (p = 0.04) for increasing quartile of Alzheimer disease genetic risk score (AD-GRS) and worse speech reception threshold(SRT) (positive change) on a continuous scale. However, only the fourth quartile had a significantly worse SRT than the first quartile of AD-GRS (reference group). Based on a linear regression of log SRT adjusted for age, sex, and 5 principal components to account for confounding by population stratification.