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.
We developed a transgenic mouse to permit conditional and selective ablation of hair cells in the adult mouse utricle by inserting the human diphtheria toxin receptor (DTR) gene into the Pou4f3 gene, which encodes a hair cell-specific transcription factor. In adult wild-type mice, administration of diphtheria toxin (DT) caused no significant hair cell loss. In adult Pou4f3 +/DTR mice, DT treatment reduced hair cell numbers to 6% of normal by 14 days post-DT. Remaining hair cells were located primarily in the lateral extrastriola. Over time, hair cell numbers increased in these regions, reaching 17% of untreated Pou4f3 +/DTR mice by 60 days post-DT. Replacement hair cells were morphologically distinct, with multiple cytoplasmic processes, and displayed evidence for active mechanotransduction channels and synapses characteristic of type II hair cells. Three lines of evidence suggest replacement hair cells were derived via direct (nonmitotic) transdifferentiation of supporting cells: new hair cells did not incorporate BrdU, supporting cells upregulated the pro-hair cell gene Atoh1, and supporting cell numbers decreased over time. This study introduces a new method for efficient conditional hair cell ablation in adult mouse utricles and demonstrates that hair cells are spontaneously regenerated in vivo in regions where there may be ongoing hair cell turnover.
Burnout is widely prevalent among U.S. otolaryngology residents and is present at greater levels than those seen in chairs or faculty of the same specialty. Work hours predict emotional exhaustion, and adherence to the ACGME 80-hour workweek may help protect against burnout and its deleterious consequences in residents of all specialties.
The capacity of adult mammals to regenerate sensory hair cells is not well defined. To explore early steps in this process, we examined reactivation of a transiently expressed developmental gene, Atoh1, in adult mouse utricles after neomycin-induced hair cell death in culture. Using an adenoviral reporter for Atoh1 enhancer, we found that Atoh1 transcription is activated in some hair cell progenitors (supporting cells) three days after neomycin treatment. By 18 days post-neomycin, the number of cells with Atoh1 transcriptional activity increased significantly, but few cells acquired hair cell features (i.e., accumulated ATOH1 or myosin VIIa protein or developed stereocilia). Treatment with DAPT, an inhibitor of γ-secretase, reduced notch pathway activity, enhanced Atoh1 transcriptional activity, and dramatically increased the number of Atoh1-expressing cells with hair cell features, but only in the striolar/juxtastriolar region. Similar effects were seen with TAPI-1, an inhibitor of another enzyme required for notch activity (TACE). Division of supporting cells was rare in any control or DAPT-treated utricles. This study shows that mature mammals have a natural capacity to initiate vestibular hair cell regeneration and suggests that regional notch activity is a significant inhibitor of direct transdifferentiation of supporting cells into hair cells following damage.
There is a high prevalence of voice problems in older people, with a large proportion having significantly impaired quality of life related to their dysphonia. General health measures do not reflect V-RQOL, and many individuals may wrongly attribute dysphonia to age-related change alone. Administration of validated instruments for assessing dysphonia is encouraged, because direct questions regarding voice difficulties may not be sensitive to the severity of vocal impairment.
Dysphagia is an important problem for the elderly. While well characterized in acutely ill populations, the prevalence and quality-of-life changes associated with dysphagia remain poorly defined in the community geriatric population. This study recruited individuals 65 years and older from an independent-living facility. Two validated questionnaires were used: the M.D. Anderson Dysphagia Inventory (MDADI) and the general health Short Form-12 survey (SF-12v2). Each participant also answered two questions: "Do you have difficulties with swallowing?" and "Do you think that swallowing difficulties are a natural part of aging?" Fifteen percent of subjects reported difficulties with swallowing. Of these, over half suffered substantial quality-of-life impairment in one or more domains of the MDADI. With respect to the second question, 23.4% of subjects believed dysphagia to be a normal part of aging, 37.4% did not. The SF-12v2 only weakly correlated with the MDADI in this population. In conclusion, there is a relatively high prevalence of dysphagia in the community-based geriatric population; significant quality-of-life impairment is a frequent finding. General health measures do not appear to be sensitive to swallowing-related quality of life. Finally, individuals may inaccurately ascribe swallowing problems to normal aging, supporting the role of community education about dysphagia in the elderly.
Burnout was prevalent among US academic otolaryngologists, although levels were lower than those of otolaryngology chairs and residents. Modification of risk factors, such as allowing sufficient faculty time for research and administrative activities, should be undertaken to curb the development of burnout and its deleterious sequelae.
IMPORTANCE Age-related hearing loss (HL) is a common and treatable condition that has been associated with cognitive impairment. The level of hearing at which this association begins has not been studied to date. OBJECTIVE To investigate whether the association between hearing and cognition is present among individuals traditionally classified as having normal hearing.
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