Genetics of age-related hearing loss

Age-related hearing loss (ARHL) has recently been confirmed as a common complex trait, that is, it is heritable with many genetic variants each contributing a small amount of risk, as well as environmental determinants. Historically, attempts to identify the genetic variants underlying the ARHL have been of limited success, relying on the selection of candidate genes based on the limited knowledge of the pathophysiology of the condition, and linkage studies in samples comprising related individuals. More recently genome-wide association studies have been performed, but these require very large samples having consistent and reliable phenotyping for hearing loss (HL), and early attempts suffered from lack of reliable replication of their findings. Replicated variants shown associated with ARHL include those lying in genes GRM7, ISG20, TRIOBP, ILDR1, and EYA4. The availability of large biobanks and the development of collaborative consortia have led to a breakthrough over the last couple of years, and many new genetic variants associated with ARHL are becoming available, through the analysis publicly available bioresources and electronic health records. These findings along with immunohistochemistry and mouse models of HL look set to help disentangle the genetic architecture of ARHL, and highlight the need for standardization of phenotyping methods to facilitate data sharing and collaboration across research networks.     

Nox3-Derived Superoxide in Cochleae Induces Sensorineural Hearing Loss

Reactive oxygen species (ROS) produced by NADPH oxidases (Nox) contribute to the development of different types of sensorineural hearing loss (SNHL), a common impairment in humans with no established treatment. Although the essential role of Nox3 in otoconia biosynthesis and its possible involvement in hearing have been reported in rodents, immunohistological methods targeted at detecting Nox3 expression in inner ear cells reveal ambiguous results. Therefore, the mechanism underlying Nox3-dependent SNHL remains unclear and warrants further investigation. We generated Nox3-Cre knock-in mice, in which Nox3 was replaced with Cre recombinase (Cre). Using Nox3-Cre;tdTomato mice of either sex, in which tdTomato is expressed under the control of the Nox3 promoter, we determined Nox3-expressing regions and cell types in the inner ear. Nox3-expressing cells in the cochlea included various types of supporting cells, outer hair cells, inner hair cells, and spiral ganglion neurons. Nox3 expression increased with cisplatin, age, and noise insults. Moreover, increased Nox3 expression in supporting cells and outer hair cells, especially at the basal turn of the cochlea, played essential roles in ROS-related SNHL. The extent of Nox3 involvement in SNHL follows the following order: cisplatin-induced hearing loss > age-related hearing loss > noise-induced hearing loss. Here, on the basis of Nox3-Cre;tdTomato, which can be used as a reporter system (Nox3-Cre^+/−;tdTomato^+/+ and Nox3-Cre^+/+;tdTomato^+/+), and Nox3-KO (Nox3-Cre^+/+;tdTomato^+/+) mice, we demonstrate that Nox3 inhibition in the cochlea is a promising strategy for ROS-related SNHL, such as cisplatin-induced HL, age-related HL, and noise-induced HL.SIGNIFICANCE STATEMENT We found Nox3-expressing regions and cell types in the inner ear, especially in the cochlea, using Nox3-Cre;tdTomato mice, a reporter system generated in this study. Nox3 expression increased with cisplatin, age, and noise insults in specific cell types in the cochlea and resulted in the loss (apoptosis) of outer hair cells. Thus, Nox3 might serve as a molecular target for the development of therapeutics for sensorineural hearing loss, particularly cisplatin-induced, age-related, and noise-induced hearing loss.     

Evidence for independent peripheral and central age-related hearing impairment

Deleterious age-related changes in the central auditory nervous system have been referred to as central age-related hearing impairment (ARHI) or central presbycusis. Central ARHI is often assumed to be the consequence of peripheral ARHI. However, it is possible that certain aspects of central ARHI are independent from peripheral ARHI. A confirmation of this possibility could lead to significant improvements in current rehabilitation practices. The major difficulty in addressing this issue arises from confounding factors, such as other age-related changes in both the cochlea and central non-auditory brain structures. Because gap detection is a common measure of central auditory temporal processing, and gap detection thresholds are less influenced by changes in other brain functions such as learning and memory, we investigated the potential relationship between age-related peripheral hearing loss (i.e., audiograms) and age-related changes in gap detection. Consistent with previous studies, a significant difference was found for gap detection thresholds between young and older adults. However, among older adults, no significant associations were observed between gap detection ability and several other independent variables including the pure tone audiogram average, the Wechsler Adult Intelligence Scale-Vocabulary score, gender, and age. Statistical analyses showed little or no contributions from these independent variables to gap detection thresholds. Thus, our data indicate that age-related decline in central temporal processing is largely independent of peripheral ARHI.     

特发性震颤听力障碍特点及其本质分析

目的部分特发性震颤(ET)患者存在听力障碍,但是针对性研究较少。通过对ET患者听力障碍特点的研究,推测ET本质特征,为ET的临床诊疗提供可供参考的策略。方法采用平行组设计,选取曲靖市第二人民医院神经内科住院部和门诊73名ET患者(146耳)和60名健康体检对照者(120耳),分别进行简易智力状态检查量表(MMSE)评分、问卷调查、纯音听力测试(PTA)和畸变产物耳声发射(DPOAE)检测,同时测定DPOAE的幅值。结果调查问卷中ET组听力下降耳数与对照组比较,差异有统计学意义(P=0.027);客观听力测试中,ET组DPOAE和PTA检出听力下降耳数与对照组比较,差异有统计学意义(P=0.019,P=0.046)。问卷调查中ET组耳鸣发生率与对照组比较,差异有统计学意义(P=0.013);ET组者在高频耳鸣发生率与对照组比较,差异有统计学意义(P=0.000)。ET病程与DPOAE下降幅值之间关系回归分析结果显示,两者呈线性相关(r=0.948, P=0.005)。结论听力障碍可能是ET的另一个经典非运动症状(NMS),推测ET可能为神经系统变性疾病。     

Parental awareness and the detection of hearing loss

October 1998

The aim of this study was to assess the effect of a specific educative process on the accuracy of parental observation regarding the child's hearing status. The presence or absence of parental concern in two groups of subjects, one of which had undergone the educative process, was elicited by direct questioning and its accuracy checked by formal hearing assessment. The results indicate that there is no significant difference in the reliability of parental observation between the two groups. However, both groups were selected from the same high awareness district and one could postulate that the effect of the educative process was minimized because the ‘uneducated’ group, as discussed, was in fact not totally uneducated. This is supported by the high accuracy of parental suspicion in hearing impaired children in this latter group compared to that reported in other studies. These results support the use of parental observation as part of a screening programme for the detection of hearing impairment in childhood.     

Prevalence of hearing impairment in a community population of adults with learning disability: access to audiology and impact on behaviour

There is a paucity of studies exploring the frequency of problem behaviours in people with learning disability and hearing impairment. Deafness in learning disability has been described as a ‘double jeopardy‘ because the difficulties are compounded to be more than the sum of their parts. The aim of the study was to ascertain the prevalence of hearing impairment in a community population of adults with learning disability and then investigate their access to audiology. We also aimed to collect information on the prevalence of problem behaviours in this population and explore links between hearing impairment and the use of hearing aids and problem behaviours. The prevalence of hearing impairment was 9.2%, 70% had been seen by audiology services at some time in their life but only 24% had ongoing assessments and hearing‐aid maintenance. Sixty‐two percent of the population had problem behaviours and 34% had self‐injurious behaviour. The high prevalence of problem behaviours and self‐injurious behaviour found in this population compared with other studies suggests a need for further research. These findings also reveal that the hearing status of people with a learning disability continues to be overlooked as the deafness often gets lost among their other problems.     

Association between depression and tinnitus in a nationally representative sample of US older adults

Objectives: Few population-based studies examining the association between tinnitus and depression among older adults have been conducted. Therefore, the purpose of this study was to examine the association between tinnitus and depression among a nationally representative sample of US older adults.

Methods: Data from the 2005–2006 National Health and Nutrition Examination Survey was used. 696 older adults (70–85 yr) completed questionnaires on tinnitus and depression, with depression assessed using the Patient Health Questionnaire-9.

Results: After controlling for firearm use, age, gender, race–ethnicity, cardiovascular/stroke history, diabetes, smoking status, body mass index, physical activity, noise exposure and elevated blood pressure, there was a significant positive association (beta coefficient: 1.28, 95% CI: 0.26–2.29, p = 0.01) between depression and tinnitus being at least a moderate problem, suggesting that those who perceived their tinnitus to be a moderate problem were more likely to be depressed than those perceiving it to be a small or no problem. Additionally, after adjustments, those who were bothered by tinnitus when going to bed were 3.06 times more likely to be depressed than those who were not bothered by tinnitus when going to bed (OR = 2.44, 95% CI: 1.03–5.76, p = 0.04).

Conclusion: These findings suggest that individuals who perceive their tinnitus to be a problem or have problems with tinnitus when going to bed may be in need of intervention to prevent or reduce their depression symptoms so as to ensure that other areas of their life are not negatively influenced.     

Deficits in comprehending wh-questions in children with hearing loss – the contribution of phonological short-term memory and syntactic complexity

The aim of the study is to investigate if German children with hearing loss (HL) display persisting problems in comprehending complex sentences and to find out whether these problems can be linked to limitations in phonological short-term memory (PSTM). A who-question comprehension test (picture pointing) and a nonword repetition (NWR) task were conducted with 21 German children with bilateral sensorineural HL (ages 3–4) and with age-matched 19 normal hearing (NH) children. Follow-up data (ages 6–8) are reported for 10 of the children with HL. The data reveal that the comprehension of who-questions as well as PSTM was significantly more impaired in children with HL than in children with NH. For both groups of participants, there were no correlations between question comprehension scores and performance in the NWR test. Syntactic complexity (subject vs. object question) affected question comprehension in children with HL, however, these problems were overcome at school age. In conclusion, the data indicate that a hearing loss affects the comprehension of complex sentences. The observed problems did, however, not persist and were, therefore, unlikely to be caused by a genuine syntactic deficit. For the tested wh-questions, there is no indication that syntactic comprehension problems of children with HL are due to limitations in PSTM.     

Ultrastructural defects in stereocilia and tectorial membrane in aging mouse and human cochleae

The aging cochlea is subjected to a number of pathological changes to play a role in the onset of age-related hearing loss (ARHL). Although ARHL has often been thought of as the result of the loss of hair cells, it is in fact a disorder with a complex etiology, arising from the changes to both the organ of Corti and its supporting structures. In this study, we examine two aging pathologies that have not been studied in detail despite their apparent prevalence; the fusion, elongation, and engulfment of cochlear inner hair cell stereocilia, and the changes that occur to the tectorial membrane (TM), a structure overlying the organ of Corti that modulates its physical properties in response to sound. Our work demonstrates that similar pathological changes occur in these two structures in the aging cochleae of both mice and humans, examines the ultrastructural changes that underlie stereocilial fusion, and identifies the lost TM components that lead to changes in membrane structure. We place these changes into the context of the wider pathology of the aging cochlea, and identify how they may be important in particular for understanding the more subtle hearing pathologies that precede auditory threshold loss in ARHL.     

High prevalence of hearing disorders at the Special Olympics indicate need to screen persons with intellectual disability

Background Persons with intellectual disabilities (ID) are at increased risk for hearing impairment which often remains undetected. If left untreated, such hearing impairments may worsen the social and communicative problems of these persons. The aims of this study are to determine the prevalence of hearing impairment, to specify type and degree of hearing loss, and to evaluate the sensitivity and specificity of the screening in this population. Methods During the German Special Olympics Summer Games 2006, 552 athletes with ID had their hearing screened according to the international protocol of Healthy Hearing, Special Olympics. This screening protocol includes otoscopy, measurement of distortion product otoacoustic emissions, and – if necessary – tympanometry and pure tone audiometry (PTA) screening at 2 and 4 kHz. Additionally, 195 athletes underwent a full diagnostic PTA. The results of the screening and diagnostic PTA were compared. Results Of the 524 athletes who completed the screening protocol, 76% passed and 24% failed it. Ear wax was removed in 48% of all athletes. 42% of the athletes were recommended to consult an otolaryngologist or an acoustician. Of the 99 athletes whose screening-based suspicion of a hearing loss was confirmed with diagnostic PTA, 74 had an undetected hearing loss. The correlation (Cramer's V) between screening and diagnostic PTA was .98. The sensitivity of the screening was 100% and the specificity 98%. Discussion The screening reliably detects hearing disorders among persons with ID. The prevalence of hearing impairment in this population is considerably higher than in the general population, and the proportion of undetected hearing impairments is large, even among people with only mild and moderate ID, as examined in this study. Therefore, a screening is highly recommended, and special attention from caregivers and professionals as well as regular hearing assessment and standard therapy programmes are required for persons with ID.     

Dendritic orientation and laminar architecture in the rabbit auditory thalamus

A laminar organization composed of the dendritic fields of principal neurons and afferent axonal arbors has been proposed as the anatomical substrate for the frequency map at several levels of the mammalian central auditory system, including the inferior colliculus and medial geniculate body (MGB). In contrast to the auditory thalamus in most mammals, the ventral division of the rabbit medial geniculate body (MGV) has cellular laminae visible in routine Nissl stains, allowing a direct comparison of the laminar organization with the dendritic architecture and frequency organization. In total 30 presumptive relay neurons in the MGV were labeled with the juxtacellular recording method, and their dendritic arbors were fully reconstructed from serial sections with the aid of a computer microscope. The spatial organization of MGV dendritic fields was analyzed using the dendritic prism, dendritic stick, and fan-in projection methods. Quantitative spatial analyses revealed that, for MGV neurons in the central pars lateralis subdivision, the major axis of the dendritic fields (approximately 29 degrees relative to the horizontal plane) was closely aligned with that of the Nissl laminae (approximately 25 degrees). Both were oriented orthogonally to the tonotopic axis. In contrast, cells in the pars ovoidea had their major axis of orientation parallel to the anteroposterior axis of the brain. Although a bitufted dendritic field was the norm, it was not uncommon for MGV neurons to have pronounced spatial asymmetries in their dendritic fields. A model is presented that incorporates cellular laminae and oriented dendritic growth to form frequency-related slabs within the MGV.     

The prevalence and phenomenology of auditory hallucinations among elderly subjects attending an audiology clinic

BACKGROUND: Studies of auditory hallucinations are scant. METHOD: To determine the prevalence and phenomenology of auditory hallucinations among elderly subjects with hearing impairment. OBJECTIVE: We surveyed 125 men and women aged 65 years and over referred to the Audiology department of a university-affiliated primary acute-care hospital. RESULTS: The prevalence of auditory hallucinations was 32.8% (95% confidence interval (CI) 24.7-41.8). These hallucinations represented a spectrum of phenomenology from elementary personal impressions to complex percepts. The types of auditory hallucinations included humming or buzzing (35.9%), shushing (12.8%), beating or tapping (10.6%), ringing (7.7%), other individual sounds (15.4%), multiple sounds (12.6%), voices (2.5%) or music (2.5%). Subjects with any type of hallucination were younger and had poorer discrimination scores in the left ear and impaired binaural discrimination with lip-reading. Subjects with hallucinations that had more qualities of a true percept heard different types of sounds and had lower reflex thresholds and better air conduction in the right ear. CONCLUSION: Auditory hallucinations are frequent in elderly subjects with hearing impairment and seem to be associated with younger age and asymmetrical hearing impairment.     

Cortical auditory evoked potentials in unsuccessful cochlear implant users

In some cochlear implant users, success is not achieved in spite of optimal clinical factors (including age at implantation, duration of rehabilitation and post-implant hearing level), which may be attributed to disorders at higher levels of the auditory pathway. We used cortical auditory evoked potentials to investigate the ability to perceive and discriminate auditory stimuli in 10 unsuccessful implant users aged 8–10 years (CI) and 10 healthy age-matched controls with normal hearing (NH). Pure tones (1 and 2 kHz) and double consonant-vowel syllables were applied. The stimuli were presented in an oddball paradigm that required the subjects to react consciously. The latencies and amplitudes of the P1, N1, P2, N2 and P3 waves were analyzed, in addition to reaction times and number of responses. Significant differences in the average response times and number of responses were observed between the CI and NH groups. The latencies also indicate that the CI group took longer to perceive and discriminate between tonal and speech auditory stimuli than the NH group.