高血黏和血脂对老年人听力影响的观察

目的探讨高血黏和高血脂对老年人听力的影响。方法按血清检测结果分组,对照组87例,高黏血症组68例,高血脂症组82例,进行纯音听阈测试。结果纯音听阈高黏血症组、高血脂症组各频率均值均显著高于对照组。结论高黏血症、高血脂症对老年人的听觉系统可造成损害,预防和治疗高黏血症、高血脂症是预防和延缓老年性耳聋的重要措施之一。     

Cochlear mitochondrial DNA3867bp deletion in aged mice

目的　探讨老龄小鼠耳蜗mtDNA缺失情况 ,明确老龄小鼠耳蜗mtDNA缺失的位置。方法　应用套式PCR和DNA测序技术对不同月龄 12 9/CD1杂交小鼠耳蜗 31个 (2月龄 7个 ,7- 10月龄 16个 ,17- 19月龄 8个 )进行定性及定量检测。结果　 1 小鼠耳蜗mtDNA386 7bp大片缺失 ,缺失发生在nt910 3-nt12 970之间 ,其两侧nt90 89-nt910 3和nt12 95 6-nt12 970为核苷酸完全相同的 15bp重复序列。 2 随着小鼠月龄的增加 ,耳蜗mtDNA386 7bp缺失发生率有明显增加的趋势 ,2月龄小鼠未发现缺失 (0 /7) ;17- 19月龄小鼠 (7/8)明显高于 7- 10月龄小鼠 (4/16 ) (P <0 0 1)。 3 缺失mtDNA/总mtDNA比值 ,17- 19月龄小鼠明显高于 7- 10月龄小鼠 (P <0 0 1)。结论　老龄小鼠耳蜗出现mtDNA386 7bp大片缺失可能与老年性聋发生相关     

Speech processing: from peripheral to hemispheric asymmetry of the auditory system

Language processing from the cochlea to auditory association cortices shows side-dependent specificities with an apparent left hemispheric dominance. The aim of this article was to propose to nonspeech specialists a didactic review of two complementary theories about hemispheric asymmetry in speech processing. Starting from anatomico-physiological and clinical observations of auditory asymmetry and interhemispheric connections, this review then exposes behavioral (dichotic listening paradigm) as well as functional (functional magnetic resonance imaging and positron emission tomography) experiments that assessed hemispheric specialization for speech processing. Even though speech at an early phonological level is regarded as being processed bilaterally, a left-hemispheric dominance exists for higher-level processing. This asymmetry may arise from a segregation of the speech signal, broken apart within nonprimary auditory areas in two distinct temporal integration windows--a fast one on the left and a slower one on the right--modeled through the asymmetric sampling in time theory or a spectro-temporal trade-off, with a higher temporal resolution in the left hemisphere and a higher spectral resolution in the right hemisphere, modeled through the spectral/temporal resolution trade-off theory. Both theories deal with the concept that lower-order tuning principles for acoustic signal might drive higher-order organization for speech processing. However, the precise nature, mechanisms, and origin of speech processing asymmetry are still being debated. Finally, an example of hemispheric asymmetry alteration, which has direct clinical implications, is given through the case of auditory aging that mixes peripheral disorder and modifications of central processing.     

Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis

Presbycusis, or age-related hearing loss (ARHL), is a major public health issue. About half the phenotypic variance has been attributed to genetic factors. Here, we assessed the contribution to presbycusis of ultrarare pathogenic variants, considered indicative of Mendelian forms. We focused on severe presbycusis without environmental or comorbidity risk factors and studied multiplex family age-related hearing loss (mARHL) and simplex/sporadic age-related hearing loss (sARHL) cases and controls with normal hearing by whole-exome sequencing. Ultrarare variants (allele frequency [AF] < 0.0001) of 35 genes responsible for autosomal dominant early-onset forms of deafness, predicted to be pathogenic, were detected in 25.7% of mARHL and 22.7% of sARHL cases vs. 7.5% of controls (P = 0.001); half were previously unknown (AF < 0.000002). MYO6, MYO7A, PTPRQ, and TECTA variants were present in 8.9% of ARHL cases but less than 1% of controls. Evidence for a causal role of variants in presbycusis was provided by pathogenicity prediction programs, documented haploinsufficiency, three-dimensional structure/function analyses, cell biology experiments, and reported early effects. We also established Tmc1^N321I/+ mice, carrying the TMC1:p.(Asn327Ile) variant detected in an mARHL case, as a mouse model for a monogenic form of presbycusis. Deafness gene variants can thus result in a continuum of auditory phenotypes. Our findings demonstrate that the genetics of presbycusis is shaped by not only well-studied polygenic risk factors of small effect size revealed by common variants but also, ultrarare variants likely resulting in monogenic forms, thereby paving the way for treatment with emerging inner ear gene therapy.

Age-related hearing loss (ARHL), also known as presbycusis, is the most prevalent sensory impairment in the adult population and is 1 of the top 10 health conditions most frequently associated with disability in the elderly. According to the World Health Organization, 320 million people worldwide aged 65 and over currently suffer from hearing disability (1). Presbycusis is a progressive late-onset hearing impairment that begins after the age of 40 and mostly affects the perception of high-frequency sounds (2). Individuals initially encounter difficulties following conversations in noisy environments and localizing sound sources spatially, until they can no longer understand speech even in quiet environments (3). This disability leads to social isolation and desocialization, profoundly altering quality of life (4). Individuals face the threat of depression and cognitive decline (5, 6), resulting in a progressive loss of autonomy. There is growing evidence to suggest that hearing loss in and after middle age is the main modifiable risk factor for dementia (7).Patient management is currently based on prostheses—hearing aids and cochlear implants—which restore hearing to an acceptable level for understanding speech in relatively quiet environments, in most individuals (8). However, these devices are not very effective in noisy environments (9).Presbycusis was long thought to be a natural and inevitable consequence of aging, but like other aging processes, it actually depends on genetic and environmental factors and their interactions (10). Various environmental factors, such as noise overexposure, the use of ototoxic drugs and solvents, and smoking, have been identified as risk factors, as have several comorbid conditions, such as diabetes and hypertension (11, 12). The most prevalent environmental cause is noise overexposure, the impact of which is steadily increasing with the proportion of the world’s population living in overcrowded cities and inadequate controls over sound intensity, extending to recreational settings (13). Environmental factors are thought to account for about half the phenotypic variance of presbycusis (10). Heritability indices of 0.35 to 0.70 have been reported in studies based on hearing thresholds in twins (14), families (15, 16), or individuals with self-reported hearing impairment (17).Genetic traits and diseases represent a continuum, with the effect size of the variants involved being inversely related to the frequency of the disease-causing variant (18, 19). The spectrum ranges from monogenic diseases (attributable to one extremely rare variant with a very large effect size—100% penetrance), via near-Mendelian traits due to variants with incomplete penetrance, and conditions due to moderately rare variants of intermediate effect size to highly polygenic traits (hundreds of common variants involved, each having a very small effect size) (20). Genetic analyses have implicated several genes in presbycusis. Association studies have been performed with candidate genes selected on the basis of a putative or demonstrated role of the encoded proteins in the cochlea. For example, given the well-established role of oxidative stress induced by overexposure to noise, associations have been highlighted between presbycusis and null alleles or single-nucleotide polymorphisms (SNPs) of certain genes involved in redox homeostasis, such as GSTT1, GSTM1 (21, 22), NAT2 (21, 23, 24), CYP1A1 (21), and UCP2 (21). Similarly, the observation that women have better hearing than men, at least until menopause, led to the discovery of an association between ESRRG and ARHL in women (25). Association studies have also been conducted with genes responsible for early-adulthood deafness displaying autosomal dominant inheritance, autosomal dominant deafness (DFNA) forms of deafness, or congenital hearing impairment displaying autosomal recessive inheritance, autosomal recessive deafness (DFNB) forms of deafness. Indicative associations have been reported with KCNQ4 (DFNA2) (26), GRHL2 (DFNA28) (27, 28), ILDR1 (DFNB42), and EYA4 (DFNA10) (29). Pangenomic association studies were then performed in large cohorts of sporadic cases of presbycusis (30, 31). Genome-wide association studies (GWAS) were performed, assuming that presbycusis, as a common disorder, would probably involve common variants (minor allele frequency [AF] > 5%) with a small effect size. GWAS detected significant associations (P ≤ 5 × 10⁻⁸) between presbycusis and SNPs close to ISG20/ACAN (29), PCDH20 (32), ARHGEF28 (30), and SLC28A3 (32) and SNPs within TRIOBP (29), SIK3 (33), NID2 (30), CLRN2 (30), ARHGEF28 (30), EYA4 (30), and very recently, ILDR1 (30, 31). Furthermore, in a large GWAS study based on the UK Biobank (including data for more than 250,000 individuals between the ages of 40 and 69 y), 36 new loci were reported to be significantly associated with self-reported hearing difficulties or with the use of hearing aids (30). A recent analysis conducted and replicated in about 10,000 affected individuals identified associations with four additional genes (31). These candidate presbycusis-predisposing (CPP) genes were mostly identified on the basis of associations of ARHL with intragenic (mostly intronic) SNPs or SNPs located in close proximity to the gene. Finally, next-generation sequencing has identified monoallelic mutations predicted to be deleterious in NHERF1, SPATC1L (34, 35), and MYO6 (DFNB37) (36) in a few sporadic and familial cases of presbycusis. It has also been suggested that mutations affecting micro ribonucleic acids (miRNAs) (37, 38) and the mitochondrial genome (39, 40) are involved in presbycusis. Together, these studies suggest that presbycusis has a large polygenic component, involving many common genetic variants of small effect size, whereas a few reports have described monogenic or monogenic-like components involving very rare variants with a large effect size.Studies of common small-effect size variants are generally poorly efficient for achieving a mechanistic understanding of pathogenesis (41) unlike approaches based on large-effect size variants underlying Mendelian transmission. Furthermore, rapid progress has been made toward the development of inner ear gene therapy approaches, which are particularly suitable for treating monogenic forms of hearing impairment. We therefore investigated ultrarare variants as potential large-effect determinants likely to underlie monogenic forms of presbycusis. We used an approach focusing on severe ARHL with no identifiable risk factors or comorbidities. We selected variants in silico, based on both existing functional annotations and standard case–control comparisons of whole-exome sequencing (WES) (42) data, combined with various in silico and experimental functional tests to gain additional evidence of pathogenicity.     

Cochlear neuropathy in the rat exposed for a long period to moderate‐intensity noises

Damaging effects on the cochlea of high‐intensity acoustic overexposures have been extensively documented, but only few works have focused on the danger of moderate noise levels. Using scanning and transmission electron microscopy, we explored the noise‐induced neuroepithelial changes that occur in the cochlea of rats subjected to moderate intensities, 70 and 85 dB SPL, for an extended period of time (6 hr/day over 3 months). Although the full quota of outer and inner sensory hair cells remained present, we detected discrete abnormalities, likely resulting from metabolic impairment, in both types of hair cell within the basal region of the cochlea. In contrast, important noise‐dependent losses of spiral ganglion neurons had occurred. In addition, we found cytoplasmic accumulations of lipofuscin‐like aggregates in most of the surviving cochlear neurons. These results strongly suggest that noise levels comparable to those of certain working environments, with sufficient exposure duration, pose a severe risk to the cochlea. Moreover, our data support the notion that long‐duration exposure to moderate noise is a causative factor of presbycusis. © 2015 Wiley Periodicals, Inc.     

Public Health Perspectives on Hearing Loss and Aging Outcomes: Age-Related Hearing Loss and the Development of Cognitive Impairment and Late-Life Depression: A Scoping Overview

Age-related hearing loss (ARHL) has been connected to both cognitive decline and late-life depression. Several mechanisms have been offered to explain both individual links. Causal and common mechanisms have been theorized for the relationship between ARHL and impaired cognition, including dementia. The causal mechanisms include increased cognitive load, social isolation, and structural brain changes. Common mechanisms include neurovascular disease as well as other known or as-yet undiscovered neuropathologic processes. Behavioral mechanisms have been used to explain the potentially causal association of ARHL with depression. Behavioral mechanisms include social isolation, loneliness, as well as decreased mobility and impairments of activities of daily living, all of which can increase the risk of depression. The mechanisms underlying the associations between hearing loss and impaired cognition, as well as hearing loss and depression, are likely not mutually exclusive. ARHL may contribute to both impaired cognition and depression through overlapping mechanisms. Furthermore, ARHL may contribute to impaired cognition which may, in turn, contribute to depression. Because ARHL is highly prevalent and greatly undertreated, targeting this condition is an appealing and potentially influential strategy to reduce the risk of developing two potentially devastating diseases of later life. However, further studies are necessary to elucidate the mechanistic relationship between ARHL, depression, and impaired cognition.     

老年性聋助听器选配效果评估问卷的应用

目的:通过对已选配助听器的老年性聋患者进行助听器效果评估问卷的填写,评估其使用效果并有针对性地解决其使用中遇到的问题,提高老年人的生活质量。方法:通过面对面的方式对30例助听器验配患者进行调查和分析。应用SPSS统计学软件分析,初步评估老年性聋患者助听器的使用效果和解决其使用中遇到的问题。结果:调查结果得出老年性聋患者听力障碍问题得到显著改善,对选配的助听器总体比较满意,且听力障碍问题的改善与满意度随时间的延长持续提高。结论:效果评估问卷可以集中反映听力障碍患者助听器使用后的残障改善情况和了解患者使用助听器的满意度,可初步作为康复效果评估的一个可靠主观效果评估指标。     

Early investigational drugs for hearing loss

Introduction: Sensorineural hearing loss (HL) is becoming a global phenomenon at an alarming rate. Nearly 600 million people have been estimated to have significant HL in at least one ear. There are several different causes of sensorineural HL included in this review of new investigational drugs for HL. They are noise-induced, drug-induced, sudden sensorineural HL, presbycusis and HL due to cytomegalovirus infections.

Areas covered: This review presents trends in research for new investigational drugs encompassing a variety of causes of HL. The studies presented here are the latest developments either in the research laboratories or in preclinical, Phase 0, Phase I or Phase II clinical trials for drugs targeting HL.

Expert opinion: While it is important that prophylactic measures are developed, it is extremely crucial that rescue strategies for unexpected or unavoidable cochlear insult be established. To achieve this goal for the development of drugs for HL, innovative strategies and extensive testing are required for progress from the bench to bedside. However, although a great deal of research needs to be done to achieve the ultimate goal of protecting the ear against acquired sensorineural HL, we are likely to see exciting breakthroughs in the near future.     

Progression of hearing loss and choice of hearing aids by patients in their 60s, 70s,and 80s and older: experience in the Japanese super-aged era

Abstract

Background: Demographic data of patients with sensorineural hearing loss (SNHL) in super-aged societies are still limited.

Aims/objectives: To report audiometric statistics of SNHL and hearing aid (HA) use in patients in their 60s, 70s, and 80s and older during the super-aged era.

Material and methods: Medical charts and audiograms of 2064 older patients with SNHL who visited a Japanese University Hospital in 2007–2018 were retrospectively reviewed. Among 270 patients referred to the HA service unit (HASU), the percentage of final decisions to continue using HAs was calculated.

Results: The average pure tone thresholds on initial visit to the clinic were 56.9, 60.6, 69.4, and 82.4?dB HL in patients in their 60s, 70s, 80s, and 90s, respectively. The rates of progression were 0.25, 0.87, 1.19, and 1.37?dB/year in patients in their 50s, 60s, 70s, and 80s, respectively. The percentage of patients in HASU who chose to use HAs did not differ among the 60s (59.3%), 70s (51.2%), and 80s and older (58.2%).

Conclusions and significance: The clinical picture of patients with SNHL in their 70s and 80s differs because progression accelerates exponentially through these ages. HAs can be recommended to older adult patients in all the age groups.