Beyond Audiometric Phenotype: Toward a Differential Diagnosis for Presbycusis.

摘要

Age-related hearing loss (ARHL; presbycusis) results from degeneration of neural and/or cochlear structures. A taxonomy distinguishing presbycusis subtypes according to site of lesion was originally proposed by linking audiometric results to histopathological findings. In most cases, the pathology is complex and audiometry and word recognition scores (WRS) are insufficient to identify the location(s) of pathologies along the auditory pathway, often referred to as the site(s) of lesion. Several sophisticated tests of auditory function, with some specifically designed to inspect cochlear or neural status (e.g., distortion product otoacoustic emissions [DPOAEs] and the auditory brainstem response [ABR]) are available today but not in routine use to distinguish between presbycutic subtypes. Because there is no pre-mortem method in place to identify contributing pathologies and their relative dominance in individual cases of presbycusis, the goal of the present study is to improve differential diagnosis in the hope of providing individualized therapeutics for those suffering ARHL. In order to determine candidacy and dosing for these treatments, specific diagnoses will become crucial. This dissertation thus systematically explores an extensive test battery composed of behavioral (audiometry and speech testing) and physiological (ABR, DPOAEs, and electrocochleography) assays of auditory function in presbycutic ears. We compare these responses to data from normal hearing subjects who serve as a reference group. Quadratic (ƒ2-ƒ 1) DPOAEs are incorporated as a potential means of gaining supplementary information regarding cochlear function. As f2-f1 DPOAEs have not been studied extensively, our initial experiments were focused on determining optimal stimulus parameters to elicit them. Results show narrow stimulus frequency ratios (1.14) and moderately high stimulus levels (70 dB SPL) are ideal. We initially set out to uncover a method of diagnosis for ARHL that improves upon the "gold standard" (audiometry and WRS). Two analytical strategies (principal component and hierarchical cluster analyses) were used to evaluate various phenotyping strategies. The results provide a potential solution, revealing the feasibility of a much more detailed diagnosis of presbycusis subtypes even in this limited data set. In the future, these phenotyping techniques should be applied on an epidemiological scale and ultimately, might inform appropriate treatment methodologies for each presbycusis subtype.