A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment.

Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.

Objectives: The goals of the present study were twofold: in the first part, the prevalence and profile of hearing disability in healthy, middle-aged persons were determined by the speech, spatial, and qualities of hearing scale (SSQ). In the second part of this study, the number of SSQ items was reduced to five to make this questionnaire available for routine usage in clinical settings and for screening purposes. Methods: SSQ responses derived from 103 normal-hearing 18- to 25-year-old persons were compared with the SSQ responses of 24 clinically normal-hearing (all thresholds between 125 and 8000 Hz ≤25 dB HL) and 109 healthy, 55- to 65-year-old persons with age-related hearing impairment to determine the prevalence and profile of hearing disability. The 45 items of the SSQ were reduced to five by cluster analyses and binary logistic regression analyses. The robustness of this five-item version (SSQ5) was determined in three control populations: an adult 25- to 55-year-old population (n = 159), an ENT-patient population (n = 60), and a population of hearing aid candidates (n = 50). The feasibility of the SSQ5 for screening was compared with the feasibility of the simple question “Do you have hearing loss?” by determining, respectively, the sensitivity, specificity, and maximum achievable discriminatory power for predicting hearing status according to speech-in-noise performance. Results: Prevalence numbers showed data of healthy, middle-aged persons with significant disability, despite minimal impairment (25%) versus data of middle-aged persons with significant impairment and nevertheless, minimal disability (61%). The profile of hearing disability seemed similar in all normal-hearing and hearing-impaired subgroups (i.e., most problems with understanding speech especially in noise conditions, and least problems with sound quality). Compared with the single question: “Do you have hearing loss?” the use of the SSQ5 had 37% more maximum discriminatory power for determining hearing status category based on speech-in-noise performance in 55- to 65-year-old persons. In addition, the SSQ5 seemed robust in adult populations of different ages (89.6% correlation between the answers of the SSQ5 and SSQ45), as well as in ENT-patient populations (93.7% correlation) and hearing aid candidate populations (79.2% correlation). Conclusions: The results of this study suggest that disability measures and measures for hearing impairment cannot replace each other, but are complementary. Therefore, it is advised to implement both disability measures and impairment measures in screening and referral policies for hearing loss. To get a first impression of hearing disability, our results suggest that it is useful to ask five disability questions (SSQ5) instead of one general question like “Do you have hearing loss?”

Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Z_high and Z_low, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Z_high—SNP9 (NT_004511:g.11244177A>T) and SNP15 (NT_004511:g.11257005C>T; NP_004691:p.Ala259Ala), and one SNP for Z_low—SNP12 (NT_004511:g.11249550A>T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A>G) to SNP18 (NT_004511:g.11257509G>A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene. Hum Mutat 27(10), 1007–1016, 2006.

Objective: This review aimed to evaluate the additional benefit of pediatric cochlear implantation before 12 months of age considering improved speech and language development and auditory performance. Materials and Methods: We conducted a search in PubMed, EMBASE and CINAHL databases and included studies comparing groups with different ages at implantation and assessing speech perception and speech production, receptive language and/or auditory performance. We included studies with a high directness of evidence (DoE). Results: We retrieved 3,360 articles. Ten studies with a high DoE were included. Four articles with medium DoE were discussed in addition. Six studies compared infants implanted before 12 months with children implanted between 12 and 24 months. Follow-up ranged from 6 months to 9 years. Cochlear implantation before the age of 2 years is beneficial according to one speech perception score (phonetically balanced kindergarten combined with consonant-nucleus-consonant) but not on Glendonald auditory screening procedure scores. Implantation before 12 months resulted in better speech production (diagnostic evaluation of articulation and phonology and infant-toddler meaningful auditory integration scale), auditory performance (Categories of Auditory Performance-II score) and receptive language scores (2 out of 5; Preschool Language Scale combined with oral and written language skills and Peabody Picture Vocabulary Test). Conclusions: The current best evidence lacks level 1 evidence studies and consists mainly of cohort studies with a moderate to high risk of bias. Included studies showed consistent evidence that cochlear implantation should be performed early in life, but evidence is inconsistent on all speech and language outcome measures regarding the additional benefit of implantation before the age of 12 months. Long-term follow-up studies are necessary to provide insight on additional benefits of early pediatric cochlear implantation.