Lateralization of cochlear dysfunction as a specific biomarker of Parkinson’s disease
Authors: Sisto Renata , Viziano Andrea , Stefani Alessandro , Moleti Arturo , Cerroni Rocco , Liguori Claudio , Garasto Elena , Pierantozzi Mariangela 
Published: September 2020

Abstract
In the last decade, animal studies highlighted the sensitivity of hearing function to lack of specific cochlear dopamine receptors, while several studies on humans reported association between hearing loss and Parkinson’s disease, partially recovered after levodopa administration in de novo patients. Taken together, these observations suggest investigating the possible use of cochlear function outcome variables, particularly, otoacoustic emissions, as sensitive biomarkers of Parkinson’s disease. Any lateralization of hearing dysfunction correlated with Parkinson’s disease lateralization would 1) further confirm their association, and 2) provide a disease-specific differential outcome variable. Differential indicators are particularly useful for diagnostic purposes, because their effectiveness is not limited by physiological inter-subject fluctuations of the outcome variable. Recent advances in the acquisition and analysis techniques of otoacoustic emissions suggest using them for evaluating differential cochlear damage in the two ears.
In this study, we quantitatively evaluated hearing function in a population of subjects with Parkinson’s disease, to investigate the occurrence of hearing loss, and, particularly, whether hearing dysfunction shows lateralization correlated to motor symptoms. Pure tone audiometry and distortion product otoacoustic emissions were used as outcome variables in eighty patients (mean age 65 ± 9 years) and forty-one controls (mean age 64 ± 10 years). An advanced customized acquisition and analysis system was developed and used for otoacoustic testing, which guarantees response stability independent of probe insertion depth, and has the sensitivity necessary to accurately assess the low levels of otoacoustic response typical of elderly subjects.
To our knowledge, this is the first study introducing the distinction between ipsilateral and contralateral ear, with respect to the body side more affected by Parkinson’s disease motor symptoms. Significant asymmetry was found in the auditory function, as both otoacoustic responses and audiometric hearing levels were worse in the ipsilateral ear. Significantly worse hearing function was also observed in patients with Parkinson’s disease compared to controls, confirming previous studies. Several pathophysiological mechanisms may be hypothesized to explain asymmetric cochlear damage in Parkinson's disease, including the impairment of dopamine release and the involvement of extra-dopaminergic circuits, with the cholinergic pathway as a likely candidate.
The observed asymmetry in the audiological response of patients with Parkinson’s disease suggests that lateralization of hearing dysfunction could represent a specific non-motor signature of the disease. The possible diagnostic use of cochlear dysfunction asymmetry as a specific biomarker of Parkinson’s disease deserves further investigation, needing a more precise quantitative assessment, which would require a larger sample size.