Search Results (40)

Background: Presbycusis, also known as age-related hearing loss (ARHL), is the most frequent sensory disability affecting elderly adults worldwide. ARHL is characterized by bilateral, progressive, sensorineural hearing loss that is more pronounced at a high frequency. Conventional factors associated with ARHL include diabetes, hypertension, and a family history of hearing loss. The severity of hearing impairment varies between individuals. The defined causative molecular pathogenesis for ARHL is unknown, thus the identification of underlying pathogenic mechanisms involved in ARHL is imperative for the development of effective therapeutic approaches. Epigenetics is the study of phenotypic changes caused by the modification of gene expression rather than the alteration of a DNA sequence. While it is hypothesized that ARHL could result from undiscovered epigenetic susceptibility, there is a shortage of information on the role that epigenetic modification plays in ARHL. Here we present an investigation on the involvement of DNA methylation in ARHL. Results: Clinical, audiometric and DNA testing, and high-throughput methylation pattern screening were undertaken for ARHL patients and matched control subjects. Our results demonstrate a strong correlation between patients’ hearing measurements and methylation at CpG sites cg1140494 (ESPN) and cg27224823 (TNFRSF25). We identified 136 differentially methylated CpGs that were shared between a high and low audiometric frequency in the patient’s cohort. CpG cites in hearing loss candidate genes, KCNQ1, TMEM43, GSTM1, TCF25, and GSR, were found to be highly methylated in presbycusis patients as compared to the controls. A methylation polymerase chain reaction (PCR) assay was used to confirm methylation levels at a specific gene locus in ARHL patients and controls. Conclusions: Altered DNA methylation and its impact on gene expression has been implicated in many biological processes. By interrogating the methylation status across the genome of both hearing loss patients and those with normal hearing, our study can help to establish an association between the audiometric patterns and methylation status in ARHL, yielding new avenues for the identification of potential candidate genes for hearing loss. Full article

Background/Objectives: In the early stage of presbycusis, patients experience reduced speech perception in noisy environments despite normal audiometry, normally known as hidden hearing loss. Diagnostic indicators like the reduced amplitude of ABR wave I, elevated extended high-frequency threshold (EHT), and decreased middle ear muscle reflex (MEMR) amplitude aim to identify biomarkers of peripheral auditory pathology but remain inconsistent. Mismatch negativity (MMN) is a cortical auditory evoked potential generated when the brain detects sound changes. This study aimed to assess MMN as a diagnostic tool for hidden hearing loss in adults. Methods: Seventy-three subjects with normal hearing underwent an extended pure-tone audiogram examination ranging from 0.125 to 16 kHz and a subsequent MMN assessment with two different paradigms: a speech (ba/da) and a tone (1/2 kHz) paradigm. The MMN’s amplitude and latency were measured and analyzed. Results: The outcome shows a significant age-related effect on MMN amplitude in the speech condition (χ² = 13.0, p = 0.002). Specifically, the MMN amplitude in the 25–30-year-old group was significantly smaller than in the 20–25-year-old group (p = 0.0015, Cohen’s d = 0.63). Additionally, no further effects of age were observed on the cortical potentials examined. Also, neither tone nor speech paradigms showed a significant influence of EHT on the amplitude or latency of either MMN or P300. Conclusions: The application of MMN as an electrophysiological tool to diagnose hidden hearing loss in normal hearing adults has limitations. However, in contrast to MMN responses to tonal stimuli, the present study reveals that MMN amplitude obtained with speech stimuli may indicate early signs of central auditory deficits. Full article

Diabetes mellitus (DM) is a common chronic health condition, affecting millions of people worldwide, and its incidence is projected to increase by almost 50% in the next two decades. The effects of DM on the auditory system have been reported. However, there is limited evidence on the association between DM and middle ear pathologies. This scoping review aimed to map the available evidence and identify research gaps regarding DM and middle ear pathologies in the adult population. Five electronic databases, namely Scopus, CINAHL, MEDLINE, PubMed, and Web of Science, were searched using a combination of specific key terms. This review followed the guidelines stipulated by the Joanna Briggs Institute (JBI) methodology for scoping reviews and reporting using PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation. A thematic narrative analysis was used to synthesize key findings. Of the 1809 articles, only 2 articles met the inclusion criteria. Neither of these studies focused exclusively on middle ear pathologies in DM, but they did report incidental findings related to middle ear function. Available evidence suggests that middle ear pathologies may occur in individuals with DM, with a reported prevalence ranging from 3.1% to 19.6%. Otitis media with effusion and conductive hearing loss were common middle ear pathologies identified. Additionally, recent studies have provided new evidence suggesting ossicular joint changes in individuals with DM and a causal link between DM and acute suppurative otitis media. However, age-related hearing loss (presbycusis) and sensorineural hearing loss (SNHL) were more commonly associated with DM, with studies reporting a high prevalence of SNHL in younger to middle-aged adults with diabetes. This review highlights a significant research gap in the literature, as no studies directly investigated the relationship between DM and middle ear function as a primary focus. Further research is required to investigate this potential association using methodologies explicitly designed for middle ear assessment. While some evidence suggests a possible association, the lack of age-stratified analyses, imaging data, and comprehensive diagnostic testing limits the ability to draw strong conclusions. Further research incorporating age-based analyses, radiological assessments, and microbiome studies is needed to fully understand the potential impact of DM on middle ear health. Full article

Recent studies applying machine learning (ML) to saccade and vergence eye movements have demonstrated the ability to distinguish individuals with dyslexia, learning disorders, or attention disorders from healthy individuals or those with other pathologies. Stroke patients are known to exhibit visual deficits and eye movement disorders. This study focused on saccade and vergence measurements using REMOBI technology V3 and the Pupil Core eye tracker. Eye movement data were automatically analyzed with the AIDEAL V3 (Artificial Intelligence Eye Movement Analysis) cloud software developed by Orasis-Ear. This software computes multiple parameters for each type of eye movement, including the latency, accuracy, velocity, duration, and disconjugacy. Three ML models (logistic regression, support vector machine, random forest) were applied to the saccade and vergence eye movement features provided by AIDEAL to identify stroke patients from other groups: a population of children with learning disorders and a population with a broader spectrum of dysfunctions or pathologies (including children and adults). The different classifiers achieved macro F1 scores of up to 75.9% in identifying stroke patients based on the saccade and vergence parameters. An additional ML analysis using age-matched groups of stroke patients and adults or seniors reduced the influence of large age differences. This analysis resulted in even higher F1 scores across all three ML models, as the comparison group predominantly included healthy individuals, including some with presbycusis. In conclusion, ML applied to saccade and vergence eye movement parameters, as measured by the REMOBI and AIDEAL technology, is a sensitive method for the detection of stroke-related sequelae. This approach could be further developed as a clinical tool to evaluate recovery, compensation, and the evolution of neurological deficits in stroke patients. Full article

Background: Although hearing loss influences voice characteristics, such changes may be under-recognized during clinical consultations. This systematic review examines voice alterations in adults with post-lingual hearing loss, considering diagnostic and rehabilitative implications. Methods: A comprehensive search of PubMed, Scopus, and Google Scholar was conducted following PRISMA guidelines, targeting studies reporting quantitative data on vocal parameters in adults with sensorineural hearing loss. Exclusion criteria included pre-lingual hearing loss and non-English studies. Data extraction focused on pitch, loudness, and prosody, with study quality assessed using NIH tools. Results: Eleven case–control studies, involving 594 patients with sensorineural hearing loss and 326 control patients, were analyzed. Patients with untreated hearing loss exhibited elevated fundamental frequency, F₀ (males: 158–169 Hz; females: 206–251 Hz) and loudness levels (males: 79–96 dB; females: 89–116 dB) compared to controls (F₀—males: 75–150 Hz; females: 150–300 Hz; loudness—males: 30–70 dB; females: 40–68 dB). Alterations in jitter, shimmer, and maximum phonation time (MPT) contributed to the distinct “hearing loss voice”. Cochlear implants (CIs) and hearing aids improved vocal parameters, with CIs reducing F₀ by approximately 12–15 Hz. Continuous hearing aid use normalized pitch and loudness within four months. Prosody alterations, such as monotone speech, were reported in long-term cases. In noisy environments, individuals with hearing loss exhibited exaggerated increases in pitch and loudness, indicative of compensatory mechanisms. Conclusions: Post-lingual hearing loss disrupts the central regulation of voice, altering pitch, loudness, and other vocal parameters. Recognizing these changes, particularly in noisy environments, could facilitate the early diagnosis and timely rehabilitation of hearing deficits, potentially mitigating associated risks of cognitive decline. Full article

Background: Vestibular Hypofunction (VH) and hearing loss can affect quality of life and lead to disability, especially in the elderly. Studies investigating presbycusis and vestibular function in the aging population have been conducted separately, but few have examined the combination of both conditions in older patients, with inconsistent results that may be due to small sample sizes or heterogeneity in the methods used to assess vestibular function. We aimed to characterize the occurrence of VH in patients with presbycusis using the video head impulse test (vHIT), which is a specific and reliable assessment tool for VH. Methods: A prospective, cross-sectional study of 200 individuals was conducted at Hamad Medical Corporation-Qatar in Doha, Qatar. Adults aged 50 years and older with bilateral age-related hearing loss were screened for eligibility and those who were eligible completed the vHIT. Patient history, demographics, audiological and clinical data were collected. VH was defined as vestibulo-ocular reflex (VOR) gain of <0.79 and presence of corrective saccades. Results: In our study population, (n = 200 mean age 64.1 ± 8.4 [Range = 37], 31.5% females), VH was identified in 12 out of 200 patients (6.0%, 95% CI: 3.3–10.1) with bilateral age-related hearing loss (ARHL), equivalent to approximately 1 in 17 patients. VH was detected in the left ear in 11 patients (5.5%, 95% CI: 2.9–9.9), the right ear in five patients (2.5%, 95% CI: 0.8–5.8), and bilaterally in four patients (2.0%, 95% CI: 0.6–5.4). Conclusions: In our study population, vestibular hypofunction was observed in 6% of patients with bilateral symmetrical age-related sensorineural hearing loss, suggesting that vestibular screening may be useful in this population at risk. Full article

Presbycusis, also referred to as age-related hearing loss (ARHL), is a multifaceted condition caused by the natural aging process affecting the auditory system. Genome-wide association studies (GWAS) in human populations can identify potential genes linked to ARHL. Despite this, our knowledge of the biochemical and molecular mechanisms behind the condition remains incomplete. This study aims to evaluate a potential protective tool for ARHL treatment by comparing human blood-based target gene-miRNA associations regulated in ARHL. To identify promising target genes for ARHL, we utilized an mRNA assay. To determine the role of miRNA in ARHL, we investigated the expression profile of miRNA in whole blood in ARHL patients with real-time polymerase chain reaction (RT-qPCR). A reporter gene assay was performed to confirm the regulation of candidate genes by microRNA. Through RT-qPCR validation analysis, we finally confirmed the relationship between ARHL and the role of the interferon-gamma (IFNG) gene. This gene can be regarded as an age-related gene. Through gene ontology (GO) analysis, it has been found that these genes are enriched in pathways related to apoptosis. Among them, IFNG induces an inflammatory response, apoptotic cell death, and cellular senescence. We found that miR-409-3p downregulates the expression of the IFNG in vitro. In addition, the downregulation of the IFNG by miRNA 409-3p promoted cell apoptosis and suppressed proliferation. In conclusion, our study produced gene signatures and associated microRNA regulation that could be a protective key for ARHL patients. IFNG genes and miR-409-3p should be investigated for their usefulness as a new biomarker for treatment modality. Full article

The integrity of the blood–labyrinth barrier (BLB) is essential for inner ear homeostasis, regulating the ionic composition of endolymph and perilymph and preventing harmful substance entry. Endothelial hyperpermeability, central in inflammatory and immune responses, is managed through complex intercellular communication and molecular signaling pathways. Recent studies link BLB permeability dysregulation to auditory pathologies like acoustic trauma, autoimmune inner ear diseases, and presbycusis. Polymorphonuclear granulocytes (PMNs), or neutrophils, significantly modulate vascular permeability, impacting endothelial barrier properties. Neutrophil extracellular traps (NETs) are involved in diseases with autoimmune and autoinflammatory bases. The present study evaluated the impact of NETs on a BLB cellular model using a Transwell^® setup. Our findings revealed a concentration-dependent impact of NETs on human inner ear-derived endothelial cells. In particular, endothelial permeability markers increased, as indicated by reduced transepithelial electrical resistance, enhanced dextran permeability, and downregulated junctional gene expression (ZO1, OCL, and CDH5). Changes in cytoskeletal architecture were also observed. These preliminary results pave the way for further research into the potential involvement of NETs in BLB impairment and implications for auditory disorders. Full article

Aging, a complex process marked by molecular and cellular changes, inevitably influences tissue and organ homeostasis and leads to an increased onset or progression of many chronic diseases and conditions, one of which is age-related hearing loss (ARHL). ARHL, known as presbycusis, is characterized by the gradual and irreversible decline in auditory sensitivity, accompanied by the loss of auditory sensory cells and neurons, and the decline in auditory processing abilities associated with aging. The extended human lifespan achieved by modern medicine simultaneously exposes a rising prevalence of age-related conditions, with ARHL being one of the most significant. While our understanding of the molecular basis for aging has increased over the past three decades, a further understanding of the interrelationship between the key pathways controlling the aging process and the development of ARHL is needed to identify novel targets for the treatment of AHRL. The dysregulation of molecular pathways (AMPK, mTOR, insulin/IGF-1, and sirtuins) and cellular pathways (senescence, autophagy, and oxidative stress) have been shown to contribute to ARHL. However, the mechanistic basis for these pathways in the initiation and progression of ARHL needs to be clarified. Therefore, understanding how longevity pathways are associated with ARHL will directly influence the development of therapeutic strategies to treat or prevent ARHL. This review explores our current understanding of the molecular and cellular mechanisms of aging and hearing loss and their potential to provide new approaches for early diagnosis, prevention, and treatment of ARHL. Full article

Background and Objectives: Although different hypotheses have been proposed over time, there is a dearth of information on factors able to predict the response to treatment for idiopathic sudden sensorineural hearing loss (ISSNHL) and hearing recovery. The aim of this study was to apply univariate and multivariate statistical models in a retrospective clinical setting of patients given therapy for ISSNHL at our tertiary academic audiological centers to investigate the prognostic value of clinical signs, symptoms, and comorbidities in relation to hearing recovery. Materials and Methods: The inclusion criteria were: history of ISSNHL diagnosed and treated at the Padova or Modena tertiary academic audiological centers; age ≥ 18 years; availability of clinical and audiological outcome data. The exclusion criteria were: hearing loss in acoustic schwannoma, endolymphatic hydrops, meningitis, trauma (head trauma, temporal bone fracture, acoustic trauma), barotrauma, perilymphatic fistula; exposure to noise levels ≥ 80 dB in the work environment; any unilateral or bilateral hearing loss (except for presbycusis) prior to ISSNHL diagnosis; any disorders affecting the external or middle ear; any previous ear surgery; refusal to make medical data available for research purposes. Eighty-six consecutive patients (38 females, 48 males; median age: 58 years; interquartile range: 47.00–69.00 years) were included. A systemic steroid therapy was administered to all patients, either orally with prednisone or intravenously with methylprednisolone. Second-line therapy included intratympanic steroid injections and/or hyperbaric oxygen therapy. Results: A multivariate logistic regression model was used, including the non-multicollinear clinical and audiological variables, which showed a p-value < 0.10 at the univariate analyses (namely age at diagnosis, time to diagnosis, oral steroid dose, and PTA on the affected side). Only PTA on the affected side retained its statistical significance (OR: 1.0615, 95% CI: 1.0185–1.1063, p = 0.005). Conclusions: The analysis of our data showed an association between the hearing threshold before treatment and the recovery from ISSNHL. Further studies on larger cohorts (especially in a prospective setting) are needed to shed more light on the prognostic role of clinical parameters in patients with ISSNHL. In a correct counseling setting, with regard to the patient’s concern about not being able to recover hearing, it is important to offer perspectives of appropriate hearing rehabilitation approaches. Full article

Objectives: Investigate factors contributing to the effective management of age-related hearing loss (ARHL) rehabilitation. Methods: A systematic review was conducted following PRISMA guidelines. The protocol was registered in PROSPERO (CRD42022374811). Articles were identified through systematic searches in the Scopus, PubMed, Web of Science, and Cochrane databases in May 2024. Only articles published between January 2005 and May 2024 were included. Studies were assessed for eligibility by two independent researchers and evaluated using the Crowe Critical Appraisal Tool v1.4 (CCAT). Results: Of the 278 articles identified, 54 were included. Three factors explain effective HA use. First, hearing aid signal processing, with directional microphones and noise reduction, improves user comfort and understanding regarding noise. Second, there is hearing aid fitting, with the NAL prescription rules as the gold standard, and bilateral, high-level HA performance for spatial localization and noise comprehension. Third, there is a patient-centered approach, using patient-related outcome measures (PROMs), questionnaires, counseling, and regular follow-up to involve patients in their therapeutic rehabilitation. Conclusions: Reaching a consensus on acoustic parameters is challenging due to variability in audiological results. Involving patients in their rehabilitation, addressing their needs and expectations, and offering individualized care are crucial. Full article

Age-related hearing loss (HL), or presbycusis, is a complex and heterogeneous condition, affecting a significant portion of older adults and involving various interacting mechanisms. Metabolic presbycusis, a type of age-related HL, is characterized by the dysfunction of the stria vascularis, which is crucial for maintaining the endocochlear potential necessary for hearing. Although attention on metabolic presbycusis has waned in recent years, research continues to identify strial pathology as a key factor in age-related HL. This narrative review integrates past and recent research, bridging findings from animal models and human studies, to examine the contributions of the stria vascularis to age-related HL. It provides a brief overview of the structure and function of the stria vascularis and then examines mechanisms contributing to age-related strial dysfunction, including altered ion transport, changes in pigmentation, inflammatory responses, and vascular atrophy. Importantly, this review outlines the contribution of metabolic mechanisms to age-related HL, highlighting areas for future research. It emphasizes the complex interdependence of metabolic and sensorineural mechanisms in the pathology of age-related HL and highlights the importance of animal models in understanding the underlying mechanisms. The comprehensive and mechanistic investigation of all factors contributing to age-related HL, including cochlear metabolic dysfunction, remains crucial to identifying the underlying mechanisms and developing personalized, protective, and restorative treatments. Full article

Background: It is assumed that speech comprehension deficits in background noise are caused by age-related or acquired hearing loss. Methods: We examined young, middle-aged, and older individuals with and without hearing threshold loss using pure-tone (PT) audiometry, short-pulsed distortion-product otoacoustic emissions (pDPOAEs), auditory brainstem responses (ABRs), auditory steady-state responses (ASSRs), speech comprehension (OLSA), and syllable discrimination in quiet and noise. Results: A noticeable decline of hearing sensitivity in extended high-frequency regions and its influence on low-frequency-induced ABRs was striking. When testing for differences in OLSA thresholds normalized for PT thresholds (PTTs), marked differences in speech comprehension ability exist not only in noise, but also in quiet, and they exist throughout the whole age range investigated. Listeners with poor speech comprehension in quiet exhibited a relatively lower pDPOAE and, thus, cochlear amplifier performance independent of PTT, smaller and delayed ABRs, and lower performance in vowel-phoneme discrimination below phase-locking limits (/o/-/u/). When OLSA was tested in noise, listeners with poor speech comprehension independent of PTT had larger pDPOAEs and, thus, cochlear amplifier performance, larger ASSR amplitudes, and higher uncomfortable loudness levels, all linked with lower performance of vowel-phoneme discrimination above the phase-locking limit (/i/-/y/). Conslusions: This study indicates that listening in noise in humans has a sizable disadvantage in envelope coding when basilar-membrane compression is compromised. Clearly, and in contrast to previous assumptions, both good and poor speech comprehension can exist independently of differences in PTTs and age, a phenomenon that urgently requires improved techniques to diagnose sound processing at stimulus onset in the clinical routine. Full article

Age-related hearing loss (ARHL), also known as presbycusis, is one of the most common neurodegenerative disorders in elderly individuals and has a prevalence of approximately 70–80% among individuals aged 65 and older. As ARHL is an intricate and multifactorial disease, the exact pathogenesis of ARHL is not fully understood. There is evidence that transcriptional dysregulation mediated by epigenetic modifications is widespread in ARHL. However, the potential role of N6-methyladenosine (m6A) modification, as a crucial component of epigenetics, in ARHL progression remains unclear. In this study, we confirmed that the downregulation of m6A modification in cochlear tissues is related to ARHL and found that the expression of the m6A methylation regulators Wilms tumour suppressor-1-associated protein (WTAP), methyltransferase-like 3 (METTL3), ALKB homologous protein 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) is decreased significantly at the mRNA and protein levels in ARHL mice. Then, we used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) to identify the differentially m6A-methylated genes in the cochlear tissues of ARHL mice. A total of 3438 genes with differential m6A methylation were identified, of which 1332 genes were m6A-hypermethylated and 2106 genes were m6A-hypomethylated in the ARHL group compared to the control group according to MeRIP-seq. Further joint analysis of RNA-Seq and MeRIP-Seq data showed that 262 genes had significant differences in both mRNA expression and m6A methylation. GO and KEGG analyses indicated that 262 unique genes were enriched mainly in the PI3K-AKT signalling pathway. In conclusion, the results of this study reveal differential m6A methylation patterns in the cochlear tissues of ARHL mice, providing a theoretical basis for further study of the pathogenesis of ARHL and potential therapeutic strategies. Full article

Age-related loss of vestibular function and hearing are common disorders that arise from the loss of function of the inner ear and significantly decrease quality of life. The underlying pathophysiological mechanisms are poorly understood and difficult to investigate in humans. Therefore, our study examined young (1.5-month-old) and old (24-month-old) C57BL/6 mice, utilizing physiological, histological, and transcriptomic methods. Vestibular sensory-evoked potentials revealed that older mice had reduced wave I amplitudes and delayed wave I latencies, indicating reduced vestibular function. Immunofluorescence and image analysis revealed that older mice exhibited a significant decline in type I sensory hair cell density, particularly in hair cells connected to dimorphic vestibular afferents. An analysis of gene expression in the isolated vestibule revealed the upregulation of immune-related genes and the downregulation of genes associated with ossification and nervous system development. A comparison with the isolated cochlear sensorineural structures showed similar changes in genes related to immune response, chondrocyte differentiation, and myelin formation. These findings suggest that age-related vestibular hypofunction is linked to diminished peripheral vestibular responses, likely due to the loss of a specific subpopulation of hair cells and calyceal afferents. The upregulation of immune- and inflammation-related genes implies that inflammation contributes to these functional and structural changes. Furthermore, the comparison of gene expression between the vestibule and cochlea indicates both shared and distinct mechanisms contributing to age-related vestibular and hearing impairments. Further research is necessary to understand the mechanistic connection between inflammation and age-related balance and hearing disorders and to translate these findings into clinical treatment strategies. Full article