Age-Related Changes of Myelin Basic Protein in Mouse and Human Auditory Nerve

Age-related hearing loss (presbyacusis) is the most common type of hearing impairment. One of the most consistent pathological changes seen in presbyacusis is the loss of spiral ganglion neurons (SGNs). Defining the cellular and molecular basis of SGN degeneration in the human inner ear is critical to gaining a better understanding of the pathophysiology of presbyacusis. However, information on age-related cellular and molecular alterations in the human spiral ganglion remains scant, owing to the very limited availably of human specimens suitable for high resolution morphological and molecular analysis. This study aimed at defining age-related alterations in the auditory nerve in human temporal bones and determining if immunostaining for myelin basic protein (MBP) can be used as an alternative approach to electron microscopy for evaluating myelin degeneration. For comparative purposes, we evaluated ultrastructural alternations and changes in MBP immunostaining in aging CBA/CaJ mice. We then examined 13 temporal bones from 10 human donors, including 4 adults aged 38–46 years (middle-aged group) and 6 adults aged 63–91 years (older group). Similar to the mouse, intense immunostaining of MBP was present throughout the auditory nerve of the middle-aged human donors. Significant declines in MBP immunoreactivity and losses of MBP+ auditory nerve fibers were observed in the spiral ganglia of both the older human and aged mouse ears. This study demonstrates that immunostaining for MBP in combination with confocal microscopy provides a sensitive, reliable, and efficient method for assessing alterations of myelin sheaths in the auditory nerve. The results also suggest that myelin degeneration may play a critical role in the SGN loss and the subsequent decline of the auditory nerve function in presbyacusis

Transient-Evoked Otoacoustic Emissions Reflect Audiometric Patterns of Age-Related Hearing Loss

Distinct forms of age-related hearing loss are hypothesized based on evidence from animal models of aging, which are identifiable in human audiograms. The Sensory phenotype results from damage (e.g., excessive noise or ototoxic drugs) to outer hair cells and sometimes inner hair cells, producing large threshold increases predominately at high frequencies. The Metabolic phenotype results from a decline in endocochlear potential that can reduce outer hair cell motility throughout the cochlea, producing gradually sloping thresholds from lower to higher frequencies. Finally, the combined Metabolic + Sensory phenotype results in low-frequency losses similar to the Metabolic phenotype and high-frequency losses similar to the Sensory phenotype. Because outer hair cell function appears to be affected differently in each phenotype, this study used audiograms from 618 adults aged 50 to 93 years ( n  = 1,208 ears) to classify phenotypes and characterize differences in transient-evoked otoacoustic emission (TEOAE) data. Significant phenotype differences were observed in frequency-band TEOAEs and configuration (intercept and slope), including large and broadly distributed TEOAE reductions for Metabolic and Metabolic + Sensory ears and more focused high-frequency TEOAE reductions for Sensory ears. These findings are consistent with metabolic declines that reduce cochlear amplification across a broad range of frequencies and more basally situated, high-frequency declines in sensory hearing loss. The results provide further validation for the classification of age-related hearing loss phenotypes based on audiograms and show human TEOAE declines that are highly consistent with animal models

Cochlear Implant Quality of Life (CIQOL): Development of a Profile Instrument (CIQOL-35 Profile) and a Global Measure (CIQOL-10 Global)

Purpose Valid, reliable, and efficient patient-reported outcome measures are needed to quantify quality of life (QOL) outcomes after cochlear implantation to supplement information obtained from performance-based outcomes. We previously developed the Cochlear Implant Quality of Life (CIQOL) item bank to serve as the source of items for subsequent instruments. This study reports the development and psychometric properties for 2 of these new instruments, the CIQOL-35 Profile and the CIQOL-10 Global. Method Cochlear implant (CI) users referred from the CIQOL Development Consortium ( = 371), consisting of 20 CI centers across the United States, provided responses to the 81-item CIQOL item bank, which are grouped into 6 QOL domains (communication, emotional, entertainment, environment, listening effort, and social). Responses to the 81 CIQOL items were analyzed using item response theory to determine individual item difficulty, discrimination, and model fit to select the set of items for the profile instrument and global measure that would optimize their measurement characteristics. Results The 35-item CIQOL-35 Profile instrument assesses outcomes represented in the 6 domains of the CIQOL final item pool. The 10-item CIQOL-10 Global measure produces a single, overall QOL score. After ensuring the upper and lower ends of the item difficulty continuum were represented (item difficulty range: -2.48 to 2.47), the items with the highest discrimination ability for each domain were selected for the CIQOL-35 Profile instrument (discrimination range: 0.67-1.37). Items were selected for the CIQOL-10 Global measure in a similar manner. Conclusion The CIQOL-35 Profile and CIQOL-10 Global instruments provide psychometrically sound and efficient measures that can be used to assess QOL in adult CI users in both clinical and research settings. Supplemental Material https://doi.org/10.23641/asha.9745010

Best Practices in the Development, Translation, and Cultural Adaptation of Patient-Reported Outcome Measures for Adults With Hearing Impairment : Lessons From the Cochlear Implant Quality of Life Instruments

This manuscript summarizes available evidence-based best practices in the development, translation, and cultural adaptation of one type of outcome measure for adults with hearing impairment, patient-reported outcome measures (PROMs). It presents the development of the Cochlear Implant Quality of Life (CIQOL) instruments and the ongoing translation and cultural adaptation of the CIQOL-35 Profile from English to French as case studies and discusses useful lessons for selecting, developing, translating, culturally adapting, and using PROMs. Relevant best practice guides are introduced, described and their steps are illustrated with examples. Future trends in hearing-related PROMs, including computerized adaptive testing, patient-reported experience measures (PREMs), economic evaluation and allocation of scarce resources, and PROMs in low-resource settings, are discussed. The manuscript concludes on the lessons that can be learned from implementation science for the successful and sustainable integration of PROMs in clinical practice.Funding Agencies|NIHUnited States Department of Health &amp; Human ServicesNational Institutes of Health (NIH) - USA [K23 DC016911]</p