Age-related hearing impairment and the triad of acquired hearing loss

Yang, Chao Hui; Schrepfer, Thomas; Schacht, Jochen

doi:10.3389/fncel.2015.00276

Cited by 116 publications

(104 citation statements)

References 129 publications

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“…However, the causes of these developments and the precise ratio of peripheral versus central contributions remain unclear (10). The severity and extent of hearing loss can be measured using pure tone audiometry, which tests the overall integrity of the hearing pathway from 125 Hz to 8 KHz.…”

Section: Pathophysiology Clinical Presentation and Evaluation Of Agmentioning

confidence: 99%

Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline

Rutherford

Brewster

Golub

et al. 2018

AJP

329

249

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Recent research has linked age-related hearing loss to impaired performance across cognitive domains and increased risk for dementia diagnosis. The data linking hearing impairment to incident late-life depression are more mixed but suggest that diminished hearing does increase risk for depression. Behavioral mechanisms may explain these associations, such as the withdrawal of older adults from situations in which they may have difficulty hearing and communicating, which may contribute to the development of social isolation, loneliness, and consequent cognitive decline and depression. At a neural level, chronic hearing loss leads to reduced activation in central auditory pathways, resulting in compensatory increased activation in the cognitive control network, dysfunctional auditory–limbic connectivity, and deafferentation-induced atrophy in frontal brain regions. These pathologic changes decrease cognitive performance and increase depression risk by reducing cognitive reserve, increasing executive dysfunction, and disrupting normative emotion reactivity and regulation. Based on the available data and informed by this model, evidence-based suggestions are proposed for clinicians treating older adults, and a research agenda is advanced to facilitate the development of rationally designed and age-appropriate psychiatric treatments for older adults with age-related hearing loss. First and foremost, treating hearing loss should be investigated as a means of improving cognitive and depressive outcomes in well-designed studies incorporating comprehensive psychiatric assessments, randomization, objective documentation of compliance, and analyses of treatment mediators that will facilitate further therapeutic development. Multimodal neuroimaging studies integrating audiometric, neuropsychological, and clinical assessments also are needed to further evaluate the model proposed.

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Section: Pathophysiology Clinical Presentation and Evaluation Of Agmentioning

confidence: 99%

Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline

Rutherford

Brewster

Golub

et al. 2018

AJP

329

249

View full text Add to dashboard Cite

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“…The death of auditory hair cells due to noise damage, ototoxins or aging is a principal cause of sensorineural hearing loss [1–3]. In contrast to other vertebrates, where supporting cells readily re-enter the cell cycle and generate hair cells after damage, the mature organ of Corti is unable to regenerate [1, 4–7].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis of Mouse Cochlear Supporting Cell Maturation Reveals Large-Scale Changes in Notch Responsiveness Prior to the Onset of Hearing

Maass

Cai

et al. 2016

PLoS ONE

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Neonatal mouse cochlear supporting cells have a limited ability to divide and trans-differentiate into hair cells, but this ability declines rapidly in the two weeks after birth. This decline is concomitant with the morphological and functional maturation of the organ of Corti prior to the onset of hearing. However, despite this association between maturation and loss of regenerative potential, little is known of the molecular changes that underlie these events. To identify these changes, we used RNA-seq to generate transcriptional profiles of purified cochlear supporting cells from 1- and 6-day-old mice. We found many significant changes in gene expression during this period, many of which were related to regulation of proliferation, differentiation of inner ear components and the maturation of the organ of Corti prior to the onset of hearing. One example of a change in regenerative potential of supporting cells is their robust production of hair cells in response to a blockade of the Notch signaling pathway at the time of birth, but a complete lack of response to such blockade just a few days later. By comparing our supporting cell transcriptomes to those of supporting cells cultured in the presence of Notch pathway inhibitors, we show that the transcriptional response to Notch blockade disappears almost completely in the first postnatal week. Our results offer some of the first molecular insights into the failure of hair cell regeneration in the mammalian cochlea.

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“…48 After a measurable noise exposure, reactive oxygen species and free radicals increase in hair cells. 49,50 In current clinical trials for sensorineural hearing loss, several studies are investigating possible benefit of various antioxidant molecules including D-methionine, N-acetylcysteine, glutathione peroxidase mimicry, and sodium thiosulfate.…”

Section: Discussionmentioning

confidence: 99%

Emerging Therapies for Sensorineural Hearing Loss

Crowson

Hertzano

Tucci

2017

Otology &Amp; Neurotology

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Objective To critically review and evaluate the proposed mechanisms and documented results of the therapeutics currently in active clinical drug trials for the treatment of sensorineural hearing loss. Data Sources U.S. National Institutes of Health (NIH) Clinical Trials registry, MEDLINE/PubMed. Study Selection & Data Extraction A review of the NIH Clinical Trials registry identified candidate hearing loss therapies, and supporting publications were acquired from MEDLINE/PubMed. Proof-of-concept, therapeutic mechanisms, and clinical outcomes were critically appraised. Data Synthesis 22 active clinical drug trials registered in the United States were identified, and six potentially therapeutic molecules were reviewed. Of the six molecules reviewed, four comprised mechanisms pertaining to mitigating oxidative stress pathways that presumably lead to inner ear cell death. One remaining therapy sought to manipulate the cell death cascade, and the last remaining therapy was a novel cell replacement therapy approach to introduce a transcription factor that promotes hair cell regeneration. Conclusion A common theme in recent clinical trials registered in the United States appears to be the targeting of cell death pathways and influence of oxidant stressors on cochlear sensory neuroepithelium. In addition, a virus-delivered cell replacement therapy would be the first of its kind should it prove safe and efficacious. Significant challenges for bringing these bench-to-bedside therapies to market remain. It is never assured that results in non-human animal models translate to effective therapies in the setting of human biology. Moreover, as additional processes are described in association with hearing loss, such as an immune response and loss of synaptic contacts, additional pathways for targeting become available.

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Age-related hearing impairment and the triad of acquired hearing loss

Cited by 116 publications

References 129 publications

Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline

Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline

Transcriptomic Analysis of Mouse Cochlear Supporting Cell Maturation Reveals Large-Scale Changes in Notch Responsiveness Prior to the Onset of Hearing

Emerging Therapies for Sensorineural Hearing Loss

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