Objective: Examine the interaction between APOE E4 and idiopathic Parkinson’s disease (PD) on age-related hearing loss using a validated web-based speech-in-noise assessment.

Background: Age is the primary risk factor for age-related hearing loss and neurodegenerative disease. Carriage of APOE E4 is associated with an increased risk of developing cognitive decline, including the processing of external stimuli (e.g., sound). However, evidence for the relationship between APOE E4 and age-related hearing loss is inconsistent, and has not been examined in a large-scale PD cohort.

Method: We sampled consented 23andMe, Inc. research participants between 50–85 years of age to complete an adaptive online speech-in-noise assessment. Participants listened to spoken digit-triplets and pressed the corresponding number keys in the order heard on their computer. Each participant’s speech recognition threshold (SRT) was calculated by estimating a logistic function and determining the SNR in decibels at 50% accuracy. Longitudinal surveys collected data on education, age, and PD diagnosis. We derived case-control status from the cumulative self-reported PD status, and SRT measurement may have preceded or followed PD diagnosis. Carriage of APOE E4 alleles was determined via genotyping. We used generalized additive models to regress SRT on PD diagnosis and APOE E4 status (carrier vs. non-carrier), adjusting for age, sex, education, 10 ancestry principal components, and genotyping platform. We applied a stratified penalized regression spline to model the nonlinear effect of age, allowing its shape to vary across combinations of PD and APOE E4 status. Main effects and interactions were compared using ANOVA.

Results: A total of n=4,282 idiopathic PD (23% APOE E4 carriers) and n=273,246 controls (25% APOE E4 carriers) were eligible for analysis. Greater hearing loss was observed in PD participants relative to controls (b=0.45dB, SE=0.05, p=2.64×10-21), and APOE E4 carriers relative to non-carriers (b=0.04dB, SE=0.01, p=2.91×10-4), when adjusted for covariates. Hearing loss increased non-linearly with age (effective degrees of freedom=7.03, p<2.22×10-308) and interacted with PD and APOE E4 status (ΔDeviance=72.85, p=0.008).

Conclusion: PD and APOE E4 carriage are associated with hearing loss and interact with age such that age-related hearing loss is more pronounced in PD participants carrying one or more APOE E4 alleles.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/interactions-between-apoe-e4-and-idiopathic-parkinsons-disease-in-age-related-hearing-loss/