Objective: Identify whether APOE E4 modulates the relationship between age and hearing loss in idiopathic Parkinson’s disease (PD).

Background: Hearing loss is associated with increased risk of PD and may serve as a prodromal marker. Hearing loss is one of the largest modifiable risk factors for dementia; however, more work is needed to develop clear clinical recommendations for hearing loss screening or intervention to reduce PD risk that also incorporate related genetic risk factors, like APOE E4.

Method: A total of 293,959 23andMe Research Institute study participants between 50–85 years of age were recruited to take a validated, web-based speech-in-noise hearing test every 6 months for 2.5 years. We calculated the participants’ speech reception thresholds (SRTs) by averaging the signal-to-noise ratios across completed trials. Saliva-based genotyping was performed on all participants. Generalized additive mixed models estimated SRT as a function of age, PD status, APOE E4 status, and their interactions. Age was entered as a non-linear term and longitudinal SRT change was accounted for by random effects. Covariates included genotyping platform, sex, education, English fluency, speaker device, and the first 10 genetic ancestry principal components. First and second-degree relatives were excluded using identical by descent segments of DNA.

Results: A total of 248,644 controls (25% E4 carriers) and 4,329 PD cases (23% E4) had complete baseline data. At baseline, age-related hearing loss increased non-linearly with age (EDF=7.22, p<0.001), and age interacted with both PD (p<0.001) and APOE E4 status (p=.008). When examining longitudinal changes, we excluded those participants with only one time-point and sampled controls randomly without replacement across 500 iterations at a 4:1 control:case ratio. This procedure resulted in 5,896 controls (26% E4) and 1,474 PD cases (21% E4) selected on each iteration. After adjusting for a practice effect over time (b=-0.16, 95% CI [-0.19, -0.13], p<0.001), we observed similar results: hearing loss increased non-linearly with age (p<0.01 in 100% of iterations), and age interacted with PD (p<0.01 in 100% of iterations) and E4 status (p for the interaction<0.05 in 73% of iterations).

Conclusion: Hearing loss increased non-linearly with age. Interactions between PD and APOE E4 with age suggest that age-related hearing loss is exacerbated in individuals with PD and APOE E4 carriers.

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