AbstractAge-related Hearing Loss Research Articles

SELF-REPORTED AND OBJECTIVE ASSESSMENT OF HEARING HANDICAP AND COGNITIVE CHALLENGES IN AGE-RELATED HEARING LOSS

Abstract Age-related hearing loss (ARHL) is a common condition in older adults, with most reporting challenges in recognizing speech-in-noise (SiN). Growing evidence also indicates cognitive alterations in this population. Concomitant examination of hearing and cognitive abilities using a combination of subjective and objective measures would be useful in characterizing the challenges faced by individuals with ARHL. We examined hearing abilities and cognitive functions in 15 individuals with bilateral mild-to-moderate untreated sensorineural ARHL (age: 70.4 ± 7.4 years, pure tone average: 31.0 ± 3.8 dB HL) and 15 age- and education-matched normal hearing controls (age: 65.7 ± 5.8 years, pure tone average: 15.4 ± 5.9 dB HL). We examined subjective ratings of hearing handicap (Hearing Handicap Inventory for Adults) and cognitive ability (Self-rating of Cognition in Everyday Activities), and objective measures of SiN (Quick Speech-In-Noise) and cognition (Montreal Cognitive Assessment [MoCA] and MoCA-memory index score [MoCA-MIS]). Our analysis revealed that individuals with ARHL self-reported a greater number of cognitive issues in everyday activities and had a higher hearing handicap score (p=.044) relative to controls. Additionally, the ARHL group performed significantly worse on SiN (p=.005) and cognitive screening (MoCA, p=.031; MoCA-MIS, p=.039). Taken together, these findings suggest that in addition to experiencing challenges with hearing abilities, individuals with mild-to-moderate ARHL also experience cognitive changes. Furthermore, these challenges are self-perceived as well as noticeable on objective testing. Our work points towards the consideration of self-report and objective assessment of cognition in geriatric hearing care, which can further inform the development of novel interventions.

HEARING LOSS AS A MODIFIABLE RISK FACTOR FOR DEMENTIA IN UK BIOBANK

Abstract Age-related hearing loss is a predictor of cognitive impairment and dementia. The mechanisms of the observed associations are unclear but could involve depletion of cognitive reserve, the occupation of cognitive resources, and lack of sensory input to the brain. Hearing loss may therefore represent a preventable or treatable causative risk factor for dementia. Indeed, many studies report on lower rates of cognitive decline among hearing aid users when compared to non-users. However, most investigations to date have been observational or with relatively short follow-ups, thus precluding clear interpretations of the underlying mechanism. In our study using UK Biobank data with n=502,386 participants followed up from ~2008 to 2021, we emulate a randomised clinical trial to probe the role of initiating the use of hearing aids in people with conductive hearing loss or with self-reported hearing difficulties in the diagnosis dementia. Diagnosis of dementia was ascertained through hospital and death records, and self-reports in such a way as to increase the positive predictive value. Among participants with hearing loss or hearing difficulties, 2,914 (2.1%) were diagnosed with dementia, compared to 4,982 (1.4%) in those without hearing loss or hearing difficulties. Additional results on the relationship between hearing aid use and dementia, and stratified analyses by sex/gender and ethnicity will be presented. We discuss the modifiability of hearing loss and recommend studies with longer follow-ups to determine the efficacy of hearing loss interventions in reducing the risk of cognitive decline and dementia.

A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss

Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function.

Neural Plasticity Induced by Hearing Aid Use.

Age-related hearing loss is one of the most prevalent health conditions in older adults. Although hearing aid technology has advanced dramatically, a large percentage of older adults do not use hearing aids. This untreated hearing loss may accelerate declines in cognitive and neural function and dramatically affect the quality of life. Our previous findings have shown that the use of hearing aids improves cortical and cognitive function and offsets subcortical physiological decline. The current study tested the time course of neural adaptation to hearing aids over the course of 6 months and aimed to determine whether early measures of cortical processing predict the capacity for neural plasticity. Seventeen (9 females) older adults (mean age = 75 years) with age-related hearing loss with no history of hearing aid use were fit with bilateral hearing aids and tested in six testing sessions. Neural changes were observed as early as 2 weeks following the initial fitting of hearing aids. Increases in N1 amplitudes were observed as early as 2 weeks following the hearing aid fitting, whereas changes in P2 amplitudes were not observed until 12 weeks of hearing aid use. The findings suggest that increased audibility through hearing aids may facilitate rapid increases in cortical detection, but a longer time period of exposure to amplified sound may be required to integrate features of the signal and form auditory object representations. The results also showed a relationship between neural responses in earlier sessions and the change predicted after 6 months of the use of hearing aids. This study demonstrates rapid cortical adaptation to increased auditory input. Knowledge of the time course of neural adaptation may aid audiologists in counseling their patients, especially those who are struggling to adjust to amplification. A future comparison of a control group with no use of hearing aids that undergoes the same testing sessions as the study’s group will validate these findings.

Downregulation of REST in the cochlea contributes to age-related hearing loss via the p53 apoptosis pathway

Age-related hearing loss (AHL) is the most common sensory disorder amongst the elderly population. Although the degeneration of spiral ganglion neurons (SGNs) and hair cells (HCs) is considered to play a critical role in AHL, the mechanism has not been fully outlined. The repressor element 1-silencing transcription factor (REST) has recently been associated with mediating cell death in neurodegenerative diseases. However, whether REST induces degeneration of cochlear HCs and SGNs to contribute to AHL remains unknown. Here, we report that REST expression was decreased in HCs and SGNs in AHL mice. Conditional deletion of Rest in HCs and SGNs of 2-month-old mice resulted in hearing loss accompanied by the upregulation of p53, TNFR1(tumor necrosis factor receptor-1), and cleaved caspase-3. The p53 inhibitor pifithrin-α significantly attenuated SGN and HC damage and rescued hearing impairment in Rest cKO mice. Furthermore, downregulation of REST by H2O2 treatment induced apoptosis in the House Ear Institute Organ of Corti 1 cell, through the upregulation of p53. In contrast, overexpression of REST reversed the changes in p53 expression. In addition, REST was further shown to bind directly to the p53 promoter site, thereby inhibiting the effect of p53. Finally, in aged mice, the p53 inhibitor significantly reduced loss of HCs and SGNs, and subsequently improved hearing. In summary, our findings indicate that REST has a protective role in AHL, and that its deficiency upregulates p53 and induces cochlear cell apoptosis, which that leads to deafness.

Association of mitochondrial DNA haplogroup and hearing impairment with aging in Japanese general population of the Iwaki Health Promotion Project

Age-related hearing loss (ARHL) is a complex multifactorial disorder. Studies in animals, including mitochondria-mutator mice, and in human suggest that oxidative stress and mitochondrial disturbance play an important role in the pathoetiology of ARHL. Mitochondrial DNA (mtDNA) haplogroups are populations with genetically similar traits, and they have been reported to affect the mitochondrial function of oxidative phosphorylation. To gain further insights into the relationships between mitochondrial haplotypes and the susceptibility to cochlear aging, in this study, we aimed to elucidate how the differences in mtDNA haplogroups may affect ARHL development in Japanese general population. We focused on early onset ARHL, as the same mtDNA haplogroup can show either a negative or positive effect on systemic co-morbidities of ARHL that appear later in life. A total of 1167 participants of the Iwaki Health Promotion Project were surveyed in 2014, and 12 major haplotype groups (D4a, D4b, D5, G1, G2, M7a, M7b, A, B4, B5, N9, and F) were selected for the analysis. A total of 698 subjects aged 30 to 65 years were included in the statistical analysis, and the hearing loss group consisted of 112 males (40.3%) and 111 females (26.4%). Multiple logistic regression analysis showed that the male subjects belonging to haplogroup A had a significantly increased risk of hearing loss, whereas the female subjects belonging to haplogroup N9 had a significantly decreased risk of hearing loss. These results suggested that the mtDNA haplogroup may be an indicator for future risk of morbidity associated with ARHL.

Retinal Vascular Density on OCT-A and Age-Related Central and Peripheral Hearing Loss in an Italian Older Population

Age-related hearing loss (ARHL) and retinal vessel changes have both been associated to neurodegeneration/dementia, suggesting a possible link between these two conditions in older age. We analyzed data on 886 older participants (65 years+, age range: 65-92 years) in the cross-sectional population-based Salus in Apulia Study. OCT-A scan was used to measure SVD and DVD of the capillary plexi of the macula in different retinal quadrants. Peripheral ARHL was defined as >40 dB HL of PTA (0.5,1,2, and 4KHz) in the worst ear, and age-related CAPD as <50% at the SSI-ICM test in at least one ear. DVD at the whole retina and at the parafoveal quadrant were inversely associated only with age-related CAPD [OR:0.93; 95%CI: 0.88-0.96 and OR:0.94; 95 CI:0.90-0.99, respectively]. The association of retinal vascular density with age-related CAPD may bring us a further step forward in understanding the biological mechanisms underlying the links between neurodegeneration/dementia and ARHL.

Working while Caring for Older Adults with Hearing Impairment and Dementia: Evidence from the NSOC

Age-related hearing loss (HL) and dementia are common among older adults. The implications of caregiving for older adults with dementia is documented. Whether the presence of HL modifies these association is unknown. We used data from the 2011 NHATS/NSOC. Hearing loss and dementia were identified among care recipients (CR). Our outcomes included: hours of care provided, and caregiver’s work activities. Among 1,013 caregivers, 456 assisted individuals without HL or dementia (HL-/D-), 229 with dementia (D+), 193 with HL, and 135 with HL and dementia (HL+/D+). In fully adjusted models, as compared to caregivers of HL-/D-, caregivers of D+ spent 39.1 hours more (95% CI: 13.6,64.6) in caregiving, caregivers of HL+/D+ spent 56.6 more hours (95% CI: 25.1,88.1). We found no differences in work activities between CR groups. The presence of HL increases the caregiving needs of adults with dementia. The additional time does not affect the labor participation of caregivers.

Downregulation of Cav3.1 T-type Calcium Channel Expression in Age-related Hearing Loss Model.

Age-related hearing loss (AHL), characterized by degeneration of cochlea structures, is the most common sensory disorder among the elderly worldwide. The calcium channel is considered to contribute to normal hearing. However, the role of the T-type voltage-activated calcium channel, Cav3.1, remains unclear in AHL. Here, we investigate the age-related change of Cav3.1 expression in the cochlea and D-gal-induced senescent HEI-OC1 cells. Cochleae from C57BL/6 mice at 2 months and 12 months of age were assessed. Senescence in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells was induced by D-gal treatment. The immunofluorescence technique was employed to investigate the distribution of Cav3.1 in vivo and in vitro. Quantitative assessment was achieved by Western blotting and real-time PCR. In comparison with 2-month-old animals, 12-month old C57BL/6 mice exhibited great loss of hair cells and elevated auditory brainstem threshold. The Cav3.1 was located in hair cells, spiral ganglion cells, lateral walls, and the expression of Cav3.1 protein and mRNA decreased in the aged cochleae. D-gal-induced senescence assay confirmed the down-regulation of Cav3.1 expression in senescent HEI-OC1 cells. Our results show that age-related down-regulated expression of Cav3.1 in the cochleae is associated with AHL and may contribute to the pathogenesis of AHL.

Hearing difficulty is linked to Alzheimer\u2019s disease by common genetic vulnerability, not shared genetic architecture

Age-related hearing loss was recently established as the largest modifiable risk factor for Alzheimer’s disease (AD), however, the reasons for this link remain unclear. We investigate shared underlying genetic associations using results from recent large genome-wide association studies (GWAS) on adult hearing difficulty and AD. Genetic correlation and Mendelian randomization (MR) analysis do not support a genetic correlation between the disorders, but suggest a direct causal link from AD genetic risk to hearing difficulty, driven by APOE. Systematic MR analyses on the effect of other traits revealed shared effects of glutamine, gamma-glutamylglutamine, and citrate levels on reduced risk of both hearing difficulty and AD. In addition, pathway analysis on GWAS risk variants suggests shared function in neuronal signalling pathways as well as etiology of diabetes and cardiovascular disease. However, after multiple testing corrections, neither analysis led to statistically significant associations. Altogether, our genetic-driven analysis suggests hearing difficulty and AD are linked by a shared vulnerability in molecular pathways rather than by a shared genetic architecture.

Effects of age-related hearing loss and hearing aid experience on sentence processing

Age-related hearing loss typically affects the hearing of high frequencies in older adults. Such hearing loss influences the processing of spoken language, including higher-level processing such as that of complex sentences. Hearing aids may alleviate some of the speech processing disadvantages associated with hearing loss. However, little is known about the relation between hearing loss, hearing aid use, and their effects on higher-level language processes. This neuroimaging (fMRI) study examined these factors by measuring the comprehension and neural processing of simple and complex spoken sentences in hard-of-hearing older adults (n = 39). Neither hearing loss severity nor hearing aid experience influenced sentence comprehension at the behavioral level. In contrast, hearing loss severity was associated with increased activity in left superior frontal areas and the left anterior insula, but only when processing specific complex sentences (i.e. object-before-subject) compared to simple sentences. Longer hearing aid experience in a sub-set of participants (n = 19) was associated with recruitment of several areas outside of the core speech processing network in the right hemisphere, including the cerebellum, the precentral gyrus, and the cingulate cortex, but only when processing complex sentences. Overall, these results indicate that brain activation for language processing is affected by hearing loss as well as subsequent hearing aid use. Crucially, they show that these effects become apparent through investigation of complex but not simple sentences.

A Preliminary Analysis of Hearing Loss and Its Association With Mild Cognitive Impairment

Age related hearing loss, or presbycusis, is a global condition that is increasing in its prevalence. Despite being one of the most common chronic conditions among the older population, there is much more to understand about its association with other aspects of physical and emotional health and well-being. Current research is suggesting that hearing loss is more prevalent in those with cognitive impairment compared to those without cognitive impairment. This study analyzed the incidence of hearing loss and its linkage to mild cognitive impairment in a community-dwelling geriatric population. With the increasing prevalence of this condition in both rural and urban communities of Alabama, it becomes a more pressing matter to understand comorbidities and risk factors for future decline in functioning. This study was conducted in an interdisciplinary geriatrics primary care outpatient clinic in a Family, Internal, and Rural Medicine department affiliated with a university medical center in the Deep South. Ninety-one participants completed the Montreal Cognitive Assessment (MoCA) and a hearing screening. Hearing screenings were conducted in quiet rooms in the medical center using Phonak hearing screening cards. Detection of 500, 1000, 2000, and 4000 Hz tones was assessed. Pearson correlation analyses demonstrated an association between hearing loss mild cognitive impairment. Poorer hearing was significantly associated with lower scores on the MoCA. Conducting behavioral health screenings like this in other primary geriatrics clinics and community settings could improve care and identification of patient needs by integrating important data regarding comorbidities and independent living.

Hearing Loss and Cognitive Decline: Causal Evidence

Age-related hearing loss (HL) has recently been associated with cognitive decline, dementia, and changes in brain structure. HL has near universal prevalence in later life (involving 80% of those over 80 years old) and is rarely treated (under 20% in the same age group). Dementia is also common in later life, carrying staggering societal implications, including a worldwide cost of over $605 billion/year. Research establishing an association between HL and cognition has included cross-sectional and prospective studies. New data show a link not only in the earliest stages of HL but also in hearing ranges still considered normal. The current evidence for an independent association between HL and impaired cognition, including a possible causal connection, will be reviewed. Plausible mechanistic pathways will be discussed with an emphasis on brain imaging biomarkers of dementia. Finally, future avenues for research and policy change will be proposed.

Hearing Care Disparities in Dementia: Access and Usability in the Coming Era of OTC Hearing Aids

Age-related hearing loss is highly prevalent among persons with dementia (PwDs) and is associated with an increased risk of neuropsychiatric symptoms. However, few use hearing aids and disparities exist. PwDs and, in particular, minority older adults, have some of the lowest rates of hearing aid use. Recent federal legislation created the designation of over-the-counter hearing aids, which will debut by 2020-2021, and represents an opportunity to advance accessibility. This presentation will share estimates of hearing aid use among community-dwelling PwDs from two cohorts, where hearing aid use ranges from 7-11% among African Americans versus 33-45% among whites. To explore this gap, the presentation will share findings from semi-structured interviews with care partners of PwDs and hearing loss around barriers and facilitators of hearing care, including device usability. With growing understanding of sensory health, a changing hearing care landscape represents a critical opening to increase access to hearing care for PwDs. Part of a symposium sponsored by the Alzheimer’s Disease Research Interest Group.

Dual Effects of Hearing Loss and Dementia on Functional Limitations in Older Adults

Age-related hearing loss (HL) is both common and associated with elevated risk for cognitive decline and poorer health. To care for an aging population, it is critical to understand the effect of coexisting HL and dementia on functional activities. The effect of co-existing dementia and self-reported HL on daily functioning were assessed. A cross-sectional analysis was performed using nationally-representative data from the 2015 National Health and Aging Trends Study consisting of U.S. adults 65+. The sample included 1,829 adults with HL (22.8%) and 5,338 adults without HL. Multivariable Poisson regression was used to model the independent effects and interaction of self-reported HL and dementia status on three validated functional activity scales (self-care, mobility, and household). All analyses adjusted for sociodemographic and medical factors. HL participants were more likely to be white, older, male, less educated (p <0.01). 8.4% had possible dementia and 6.5% had probable dementia. Respondents with HL or possible or probable dementia had significantly lower mobility, self-care, and household activity scores (p<.001 for all comparisons) compared to their peers. A small yet significant interaction was present in all models, suggesting that HL respondents with co-occurring dementia had lower mobility, self-care, and household activity scores than predicted by the independent effects of dementia and self-reported HL (p<.001 for all comparisons). Older adults with co-occurring dementia and HL are at increased risk for poor functioning and should be screened by healthcare providers. Future work should consider the impact of intervention in this vulnerable/at-risk population.

Hearing Loss in Older Adults: Implications for Cognitive Load and Brain Structure and Function

Age-related hearing loss is prevalent in two-thirds of older adults and reflects progressive impairments in cochlear function leading to impoverished peripheral neural encoding of sound. Research has demonstrated the broader implications of hearing loss for the health and functioning of older adults, particularly with respect to brain aging and dementia. This presentation will summarize current epidemiological and neuroimaging evidence for how hearing loss in older adults affects cognitive load and brain structure/function and relate this contemporary research with previous psychological studies proposing ‘information degradation’ and ‘sensory deprivation’ hypotheses of how hearing may affect cognitive function. Finally, the design of an ongoing NIA-funded randomized controlled trial (ACHIEVE- Aging and Cognitive Health Evaluation in Elders) that will determine if hearing treatment reduces the risk of cognitive decline, dementia, and brain aging in adults will be discussed. Part of a symposium sponsored by Brain Interest Group.

Presbycusis and hyperlipidemia: Is there any link?

Age related hearing loss is one of the most common chronic health conditions affecting the elderly people. With aging, risk of Presbycusis and hyperlipidemia increases. Although most studies do reach some sort of agreement, the evidence supporting a relationship between presbycusis and hyperlipidemia remains questionable. The objective of this study is to determine the association between age related hearing loss and hyperlipidemia and assess the severity of hearing loss in hyperlipidemic patients. This cross sectional analytic study was carried out at ENT Out Patient Clinic at Al Sader teaching Hospital from March 2019 to December 2019. A cross‑sectional study on 52 patients with Hyperlipidemia and 42 non Hyperlipidemic patients was carried out during March 2019 to December 2019. All patients were evaluated for hearing loss by subjecting to pure tone audiometry, blood investigations were done in form of lipid profile, blood sugars, thyroid function test, blood urea and serum creatinine levels. Group A consisted of 22 (42.3%) males and 30 (57.7%) female while group B consisted of 23 (54.8%) male and 19 (45.2%) female individuals. Audiological assessment by PTA was show that the prevalence of presbycusis among hyperlipidemic group more than non hyperlipidemic with significant statistical difference (P value &lt;0.05). Prevalence was 76.9%. In conclusion; there is statistically significant association between presbycusis and hyperlipidemia especially those with hyercholestrolemia.

Regulating Age-Related Hearing Loss with Bisphenol A via the Long Non-Coding RNA X Inactive Specific Transcript and MicroRNA-34a-5p Pathways

Age-related hearing loss (AHL) is a common, high-incidence, perceptual disease in the elderly population worldwide. Since bisphenol A (BPA) has been reported to associate with cell apoptosis, we hypothesize that BPA can inhibit the neuronal apoptosis in AHL. Forty Wistar rats were recruited to model AHL; they were then treated with different doses of BPA. We used auditory brainstem response testing to measure the BPA-induced improvement in the rats’ hearing. We examined the proliferation and apoptosis of the auditory cortical neurons in the rats with MTT assay and flow cytometry. Also, to delineate the underlying mechanism of BPA’s effect on AHL, we quantitated the expression level of long non-coding RNA X inactive specific transcript (lncRNA XIST) and miR-34a-5p in the rats’ auditory cortex with a novel method called nanoparticle PCR. We found that BPA intervention improved the hearing of AHL model rats, enhanced neuronal cell proliferation, restricted neuronal cell apoptosis, upregulated miR-34a-5p levels, and downregulated lncRNA XIST levels. The dual-luciferase reporter (DLR) assay revealed that BPA inhibited the apoptosis of auditory cortex neurons by targeting miR-34a-5p with lncRNA XIST and regulated the process of AHL. Therefore, we come to a conclusion that BPA contributes to the improvement of AHL, which may be achieved by upregulating miR-34a-5p and inhibiting the apoptosis of auditory cortex neurons via lncRNA XIST.

Age-related Hearing Loss: Recent Developments in Approaching a Public Health Challenge

Age-related hearing loss is highly prevalent and increasingly recognized as a public health priority. The purpose of this review is to summarize developments in understanding the role hearing plays in aging and new approaches to hearing health care. Growing evidence from large epidemiologic studies documents an association between hearing loss and the development of incident dementia, accelerated cognitive decline, depression, decreased quality of life, and falls, as well as increased risk of hospitalizations, health care utilization, and expenditures. Recent advances in legislation and delivery models hold promise in increasing access to hearing health care with the ultimate goal of mitigating the impact of hearing loss. With an aging population, age-related hearing loss will remain a public health priority. While progress has been made in the past decade, more research must be conducted to better understand the consequences of age-related hearing loss and the benefits of treatment, as well as expand access to hearing health care, particularly, as a potentially essential tool to aging well.

SUBCLINICAL AGE-RELATED HEARING LOSS IS INVERSELY ASSOCIATED WITH DEPRESSIVE SYMPTOMS

Age-related hearing loss (HL), defined by a pure-tone average (PTA) >25 decibels (dB) has been associated with depressive symptoms. We aimed to assess whether this association is present when hearing is better than the arbitrary, but widely-used, 25 dB threshold. The sampled population was the multicentered Hispanic Community Health Study (n=5,165). Cross-sectional data from 2008-2011 were available. Hearing was measured with pure tone audiometry. Clinically-significant depressive symptoms (CSDS) were defined by a score ≥10 on the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Participants’ mean age was 58.3 years (SD=6.2, range=50-76). Among those with classically-defined normal hearing (PTA ≤25 dB), a 10 dB increase in HL was associated with 1.26 times the odds (95% CI=1.11, 1.42) of CSDS, adjusting for age, gender, education, vascular disease, and hearing aid use (p25 dB; p<0.001). Results held even for a stricter HL cutpoint of 15 dB. Among subjects with strictly normal hearing (PTA ≤15 dB), a 10 dB increase in HL was associated with 1.47 (1.14, 1.90) times the odds of CSDS, adjusting for confounders (p<0.01). Results also held when defining CSDS by an alternative CESD-10 score ≥16. In conclusion, increasing hearing thresholds were independently associated with CSDS among adults with subclinical HL (PTA ≤25 dB). Studies investigating whether treating HL can prevent late life depression should consider a lower threshold for defining HL.