To examine hearing thresholds in senior adults of 80 years and older and compare this data to the current ISO 7029 reference values.A descriptive, prospective study testing pure-tone and speech audiometry in senior adults participating in the BUTTERFLY study or the BrUssels sTudy on The Early pRedictors of FraiLtY. A Gerontological study to identify determinants for active aging and for early stages of frailty in the oldest population. Using the formula given by ISO 7028:2017 the median value of hearing was calculated based on the sex and age of the participant and compared to the measured hearing thresholds.151 senior adults were included. The prevalence of hearing loss was 90.7% (PTA > 20 dB HL). The results were compared to the mean ISO values, calculated for every participant. Both males and females in our study population had worse hearing thresholds than could be expected based on the ISO reference values. In our study population with moderate hearing loss (PTA > 40 dB HL), 38% is underserved in term of hearing restoration healthcare and yet another 38% is unsatisfied with the result of the hearing aids. Given the vast impact on the individual and society, this is a problem in need of our attention.The ISO 7029 reference values may be an underestimation of hearing loss in senior adults of 80 years and older. Therefore we present a statistical distribution of hearing thresholds on different frequencies related to age and sex that can be used as a baseline for further development of the reference values. According to the latest Global Burden of Disease Studies , hearingWithin older adults, hearing loss has an important impact on the individual. It is not only associated with social isolation , but alsThe third and most recent edition of the International Organization for Standardization (ISO) standards for the statistical distribution of hearing thresholds related to age and sex addresses hearing thresholds for adults from 18 up to the age of, 80 years , who havA better knowledge of the hearing thresholds among the most elderly is not only of importance to the subjects themselves, but also to clinicians and researchers. For the patients, their families and the clinicians, it can be important to be aware whether or not an individual subject presents a hearing threshold that can be expected for that age, and if more than the usual supportive measures have to be provided.In this study we will determine hearing thresholds related to age and sex in otologically normal senior adults of 80 years and older in a Belgian population and compare them to the ISO hearing thresholds calculated for the same age category by using the formula given by ISO 7028:2017.The study protocol was approved by “the Committee of Medical Ethics” of the Universitair Ziekenhuis Brussel. It is an explorative, prospective, observational study that started in September 2015 with a longitudinal follow up over 2 years. This study is part of a larger gerontological study that examines various aspects of the health of senior adults over 80 years of age, including Ear, Nose and Throat (ENT) tests. The study is called the BUTTERFLY or BrUssels sTudy on The Early pRedictors of FraiLtY. The aim is to identify determinants for active aging (assets) and for early stages of frailty (deficits in reserve capacity) in the oldest population.All participants were senior adults who were over 80 years old or who turned 80 in the year of participation. They were community dwelling and well-functioning adults recruited through advertisements at the Universitair Ziekenhuis Brussel, but also in elderly care organizations, health insurance companies, general practitioners and pharmacies. Inclusion criteria were: walking independently and living at home independently. All participants underwent medical and physical testing as well as psychosocial and cognitive testing. A thorough ENT examination and audiometric analysis were part of the medical testing in this study.Exclusion criteria were an aberrant tympanometry type , ear pathology with known impact on hearing threshold  ear surgery and chronic ear pathology .Given the unreliable and unstandardized information concerning noise exposure, familial history of SNHL and the use of ototoxic medication, these were not included in the exclusion criteria.N = 181 participants, 95 males and 86 females, were interviewed and examined at the ENT Department. One hundred fifty-one participants met the inclusion criteria. Of the 30 participants who were excluded from the study, 17 had an aberrant tympanogram, 9 had a disease that is known to cause hearing loss, 4 had chronic infections and perforation of the eardrum and 4 had a history of ear surgery. There were 3 participants with more than one exclusion criterium. The diseases associated with hearing loss were very diverse: otosclerosis (n = 2), unilateral self-reported deafness (n = 2), Menière’s disease (n = 1), cholesteatoma (n = 1), vestibular schwannoma (n = 1) and sequelae of sudden deafness (n = 1). There were only 2 types of ear surgery: attico-antro-mastoidectomy (n = 2) and ossicular chain reconstruction (n = 2).During the study period from September 2015 to September 2016, a total of n = 37) of which 32 cases had a history of professional noise exposure mostly due to heavy machinery (n = 17) and police- and military work (n = 15). Among the 8 females with self-reported noise exposure, all the exposure was work related and mostly due to teaching and professional phone usage. The history of ototoxic medication use was reported in 6 participants (4%) (2 cases in the context of chemotherapy for cancer treatment and 4 cases of Quinine use). A familial history of hearing loss, whether or not with an early onset, was reported in 24 (15.9%) of the participants (Of the 151 included participants 84 (55.6%) were male and 67 (44.4%) were female. The mean age was 82.4 years old (SD ± 2.54), with a minimum age of 80 and a maximum age of 90. One hundred twenty-one (80%) participants belonged to age group 1 of which 70 (57.9%) male and 51 (42.1%) female. Thirty (20%) belonged to age group 2 of which 14 (46.7%) male and 16 female (53.3%). There were 31 hearing aid users (20.5%) and among them 12 (38.7%) were unsatisfied with the effect of their amplification. Nine (6%) participants spontaneously stated to have regular tinnitus complaints. Forty five (29.8%) participants stated that they had been exposed to noise, the majority was male  with a 226 Hz probe tone. The tympanometry graph was subcategorized by using the Liden and Jerger classification system . TympanoPure-tone audiometry included the determination of the air- and bone conduction hearing thresholds with a liminar tonal audiometric (LTA) examination using the International Organization for Standardization: ISO 8253-1:2010 methods  for pureFor the classification of hearing loss, the BIAP classification was used, as it is a well know and frequently used classification in Belgium and Europe, and is largely comparable to the grades of hearing impairment recommended by the Global Burden of Disease Expert Group on Hearing Loss  and the During speech audiometry the right and left ear were tested separately. According to the native language of the subject, Dutch or French standardized two-syllable word lists were used. The native Dutch speaking group was tested with the standardized BLU-wordlist  and the md,Y = αmd (Y – 18)βmd. “Y” is age in years, αmd and βmd are dimensionless quantities given by ISO for males and females for frequencies from 125 to 8,000 Hz  was calculated to compare the values of our measurements and the calculated ISO values using an independent t-test. All statistical analyses were performed using a level of statistical significance of 0.05.The statistical analysis was carried out using SPSS Statistics computer package, version 23. Descriptive analysis were given by frequencies and percentages for categorical data, mean (standard deviations) for continuous data. When comparing the audiometric data, the Independent sample- or Paired samples Student’s n = 2) had a 1st degree severe hearing loss. In total 50 (33.1%) of our participants had a hearing loss > 40 dB.In the better hearing ear the overall prevalence of hearing loss according to the BIAP classification (PTA > 20 dB HL) was 90.7%, this is 95.2% of all males and 85.1% of all females . Most ofp = 0.7). On the other hand, males had significantly poorer hearing than females according to the PTA (37.17 and 35.07 dB HL: p = 0.016) and the high frequency average (71.29 and 62.44 dB HL: p < 0.001). This difference can be observed in When comparing the curves of the mean air-conduction thresholds according to sex in p < 0.001), the PTA (34.74 and 42.29 dB HL: p = 0.001) and the high frequency average (66.28 and 71.72 dB HL: p = 0.031).p = 0.027, LFA: p = 0.031, HFA: p = 0.119).The analysis above needs to be interpreted with caution, as the effect of age and sex on the hearing thresholds have a significant interaction (PTA: p = 0.021) (p = 0.026) (p < 0.001)  (The effect of sex is shown in = 0.021) . Convers= 0.026) . The eff< 0.001) . This di= 0.119) .n = 31) had significantly poorer air-conduction thresholds than subjects without hearing aids (n = 120). This difference was present in the PTA frequencies (50.48 and 32.56 dB HL: p < 0.001) as well as in the low (33.44 and 24.71 dB HL: p = 0.003) and high frequencies (79.30 and 64.28 dB HL: p < 0.001). There was no significant difference in the distribution of males and females in the hearing aid user group . Conversely, when analyzing the distribution in age groups we saw that there were significantly more hearing aid users in age group 2: 43.33% vs. 14.88% in age group 1 (p = 0.01).Hearing aid users  of our participants had a hearing loss > 40 dB: these participants could all benefit from wearing hearing aids, but only 31 (62%) of them wore them. This means 19 (38%) participants with moderate hearing loss or more were undertreated by not wearing hearing aids. Moreover, when evaluating the satisfaction of hearing aid users to determine whether they benefited from their hearing aid, there were 12 (38.7%) participants unsatisfied by the effect. Therefore 38.7% of the participants with moderate hearing loss or more who wore hearing aids were undertreated as well.p = 0.188). nor did we find a significant difference in the low-(22.41 and 26.76 dB HL: p = 0.227) or high frequency averages (64.07 and 67.57 dB HL: p = 0.515) in these participants. There were no significant differences in sex  in the prevalence of tinnitus according to the Fisher’s exact test.There were 9 participants who spontaneously complained about regular tinnitus symptoms. We couldn’t detect a significant difference in the PTA of participants who did or did not complain about tinnitus (30.97 and 36.37 dB HL: p = 0.379) (p = 0.01). Therefore, the groups were analyzed in detail. In age group 2, the SRT of males was significantly poorer than that of females (49.08 and 38.50 Dbspl: p = 0.022). In age group 1, sex had no significant effect on the SRT value (36.13 and 37.76 dBSP: p = 0.429). In males, we saw that age group 2 had a significantly poorer SRT than age group 1 (49.08 and 36.13 dBSPL: p = 0.001). Females showed no significant difference according to age groups (37.76 and 38.50 dBSPL: p = 0.796). Hearing aid users had a significantly poorer SRT than subjects without hearing aids (49.47 and 35.21 dBSPL: p < 0.001).There were no significant differences between the mean SRT of the right and left ear (39.57 and 40.55 dBSPL: = 0.379) . Therefon = 7) or both (n = 4) ears. Only in age group 2 there was a difference in sex where males needed a significantly higher dB level than females (70.00 and 56.00 dB HL: p = 0.01) to reach 100%.Of all participants, 92.72% reached 100% speech recognition in each ear. In 11 (7.28%) participants, speech recognition scores did not reach 100% in one (p = 0.298). In total 61.90% of the males and 58.20% of the females showed a roll-over. This difference in sex was not significant (p = 0.738). We can conclude that there was no significant effect of age and sex on the prevalence of a roll-over.Ninety-one participants showed a roll-over in speech audiometry, 70 in age group 1 (57.85%) and 21 in age group 2 (70.00%). This difference according to age groups was not significant (p < 0.001) (We compared the results of the pure-tone and speech audiometry (PTA and SRT). This showed that the overall values of SRT were slightly higher than those of PTA; however, when looking at the interclass correlation coefficient, we saw that the PTA and SRT of the better ear had a high correlation of 0.80 (< 0.001) .In In p < 0.001) and females (387.35 and 345.23: p = 0.002).When calculating the area under the curve, the measured thresholds were overall significantly higher (or worse) than the calculated ISO thresholds in males (410.98 and 364.78: p = 0.055), 6,000 Hz (72.14 and 69.78 dB HL: p = 0.19) and 8,000 Hz (81.48 and 82.28 dB HL: p = 0.64). This means that on the following frequencies the ISO calculation was not representative for our population that had worse hearing thresholds: frequency 125 (27.61 and 22.27 dBHL: p < 0.01), 250 (25.53 and 18.46 dB HL: p < 0.001), 500 (23.15 and 17.83 dB HL: p < 0.001), 750 (25.00 and 19.95 dB HL: p = 0.001), 1,500 (35.65 and 28.98 dB HL: p < 0.001), 2,000 (39.64 and 34.81 dB HL: p = 0.008), 3,000 (49.40 and 45.26: P = 0.029) and 4,000 Hz (60.23 and 54.60 dB HL: p = 0.003).In males  our meanp < 0.001), 250 (27.61 and 17.72 dB HL: p < 0.001), 500 (27.08 and 20.83 dB HL: p < 0.001), 750 (27.68 and 23.75 dB HL: p = 0.005), 6,000 (63.78 and 57.99 dB HL: p = 0.021) and 8,000 Hz (75.74 and 64.78 dB HL: p < 0.001).In females  our meanIn our study, hearing loss (> 20 dB) was very common, affecting 90.7% of the senior adults between 80 and 90 years old. In previous studies investigating a population of 80 years and older, hearing loss (≥ 25 dB) was reported in 78.2%  to 90.0%Most studies concerning the hearing level of senior adults and ARHL only determine the prevalence of hearing loss and the general trend of hearing thresholds . FrequenIn this study we only included subjects who are 80 years and older and focus thereby specifically on the only group not covered by the ISO standards for hearing measurements. However, we have to note that the mean age was 82.4; which means that the largest part of our sample (80%) was situated in age group 1 (80–84).With the detailed percentile distribution of hearing thresholds in our older age group we hope to contribute to a wider understanding and provide data that can serve as a baseline in order to evaluate the evolution of hearing thresholds among those few people that attain unprecedented ages.Apart from the prevalence of hearing loss, we determined a representation of the statistical distribution of hearing thresholds on different frequencies related to age and sex. In This study demonstrated the deterioration of hearing after the age of 80 years. The deterioration in elderly has been described most pronounced at the middle to higher frequencies above 1,000 Hz . Our stuComparing individual hearing tests to age-matched norms gives healthcare providers the opportunity to correctly diagnose people with hearing levels that are below average for their age and sex. Diagnosing and treating hearing loss in senior adults above the age of 80 in a standardized way may prevent the consequences of hearing loss in this vulnerable population. The benefits of early diagnosis and possible treatment will not only affect the hearing capacity of the elderly, but can potentially prevent important outcomes of untreated hearing loss such as social isolation , depressOur sample included 31 hearing aid users. They had a significantly poorer pure-tone audiometry on all frequencies as well as a poorer SRT compared to participants who did not use hearing aids. This means that participants with poorer hearing were more likely to be using a hearing aid . This caIt is widely accepted that the prevalence of hearing loss is higher with increasing age. In our study we observed that the older age group indeed had a significantly poorer hearing than the younger group, and that males were more affected by age than females on all frequencies.We noticed increasing difficulties in speech recognition in our older population. It has been described that speech audiometry is significantly better in females compared to males . In our When comparing the results of the pure-tone and speech audiometry in our study we saw a high correlation between SRT and PTA, yet the overall distribution showed that the SRT was slightly higher than the PTA, or the recognition of speech was poorer than the detection of pure tones. We hypothesize that when the SRT is higher (or worse) than the PTA, there is a higher possibility of central processing problems or central presbycusis.Our audiometric data was used to investigate the link between hearing loss, hearing aid usage and cognitive decline . This stOur study has some limitations. The first is that information on the history of the participants was gathered by using a questionnaire, filled out by the participants together with the ENT specialist. All the information gathered is thus based on memory, which may not be sufficient when answering such specific questions. A recall bias must be considered, for example, while military service had been obligatory for males of that generation, only 12 of the 84 males mentioned noise exposure related to military practice. Participants could have been exposed to noise or ototoxic drugs without knowing. This is why noise exposure was not used as an exclusion criterion. This has to be considered when comparing our data to other studies where the noise-exposed participants were excluded. The interpretation of the answers by different ENT specialists while completing the questionnaire could have an influence on the standardization. Also, in our study we only have 9 participants who complained of tinnitus, although tinnitus is often linked with high frequency losses , which aAnother limitation is the fact that audiometric analysis was only performed by pure-tone and speech audiometry. Other tests like the speech perception in noise (SPIN) test could have provided more detailed results, however, the participants underwent multiple tests across hospital services in 1 day and additional tests could have led to negative effects of fatigue  and reduA third limitation is that our population was not randomly selected but had to meet the following inclusion criteria: walking independently and living at home independently. Consequently, this is not a representation of the entire 80 + -population and may lead to a bias in hearing measurements. It has been described in literature that hearing loss has an influence on functional decline . People To conclude, it should be noted that, when comparing the calculated ISO-values to our measured thresholds, these measurements were done in audiometric setting where all numbers are a multiple of 5. When calculating a mean threshold by using the ISO formula all numbers are possible.Hearing loss is a very common problem in people over 80 years of age. Our study demonstrates that a large majority (90.7%) of the senior adults suffer from hearing loss greater than 20 dB HL. In our population, males’ hearing sensitivity tends to decline more with increasing age on all frequencies with a steeply downward-sloping curve. This in contrast to females, who’s hearing sensitivity declines with a more gradually sloping curve. Our findings suggest that the ISO-values may be an underestimation of hearing loss in people of 80 years and older both in males and females. Therefore, we present a statistical distribution of hearing thresholds on different frequencies related to age and sex that can be used as a baseline for further development of reference values for this older age group. A large part of the older age group with hearing loss stay undertreated. More than one third (38%) of the participants who could benefit from hearing aid (hearing loss > 40 dB) didn’t have one, and one third of the hearing aid wearing participants was not satisfied by the effect and could potentially benefit from other hearing advancement such as cochlear implantation.The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Commissie voor Medische Ethiek Universitair Ziekenhuis Brussel. The patients/participants provided their written informed consent to participate in this study.KDR conceptualized and designed this study, analyzed data, drafted the initial manuscript, and approved the final manuscript as submitted. RVA recruited the patients and did the general medical evaluation. EL performed the audiometric testing’s at UZ Brussel, reviewed and helped with the acquisition of data. KDR and RB provided statistical analysis. IBe and IBa designed and supervised the BUTTERFLY experiment. IF, OM, VT, and FG provided critical revision. All authors reviewed and approved the final manuscript as submitted.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Although the association between balance and hearing thresholds at different frequencies in the right/left ear is crucial, it has received scant empirical attention. Balance is widely ignored when evaluating hearing in adults. This study examined the relative contribution of left versus right ear hearing at different frequencies to balance, and the mediating role of suprathreshold speech perception on age-balance associations. Pure tone hearing thresholds (500–4000 Hz), suprathreshold speech perception, balance, and risk of falling were evaluated in 295 adults. The results indicate that the right ear contributes more to balance than the left ear. This might imply dominance of the left hemisphere in processing hearing cues for balance. Frequencies within the speech range (500/1000/2000 Hz) were correlated with balance and mediated the interaction between age and balance. These results should be considered when tailoring hearing and balance rehabilitation programs. Specifically, right ear processing is significantly more efficient for speech stimuli7. In recent years, a growing body of evidence has suggested that hearing cues contribute to balance9. Studies show that auditory information can be integrated with vestibular, somatosensory, and visual signals to improve balance, orientation, and gait13. Despite its importance, to the best of our knowledge, the relative contribution of the right/left ear to balance has never been explored.Beginning with the discovery of the left-hemispheric dominance of language12 reported that external auditory input contributes meaningful information to vestibular self-motion cues in a frequency-dependent manner. They showed that auditory cues significantly improve sensitivity to self-motion perception below 0.5 Hz, whereas vestibular cues contribute more at higher frequencies. However, the ways in which hearing thresholds at different frequencies potentially influence balance control remain unclear.Shayman et al.14 and Carpenter & Campos15 recommended that future research should use real life environments and functional indices rather than relying solely on a laboratory-based approach consisting of pure-tone hearing thresholds. One of the first signs of hearing deterioration is difficulty in understanding speech in challenging everyday listening situations19. However, very little is known about the interaction between the deterioration of speech perception and balance.To improve the ecological validity of the human hearing-balance relationship Criter & Gustavson13. Early detection of balance disorders and possible interventions can potentially reduce falling and prevent its consequences13. Recent studies have shown that auditory information can be integrated with vestibular, somatosensory, and visual signals to improve balance, orientation, and gait13. However, hearing status is rarely taken into account when evaluating gait and balance9.Falling and its consequences have a significant impact on individuals  and society To respond to these needs, the current study examined the interaction between hearing and balance in a group of adults, using functional indices of hearing and balance. It then explored the relative contribution of the left versus right ear at different frequencies to balance. The findings should lead to a better understanding of the age-balance association.The descriptive statistics and inter-correlations for hearing and balance measures are presented in Tables Balance was significantly correlated with the Pure Tone Average 1 , Pure Tone Average 2 , the Words In Noise test WIN 50% SNR, and with hearing thresholds at 500 Hz, 1000 Hz, and 2000 Hz but not at 4000 Hz, in both ears. Age was significantly correlated with the PTA 1/2, WIN 50% SNR, hearing thresholds  and balance in both ears.Since there was a significant correlation between age and balance, age and hearing, and balance and hearing, the mechanism underlying the observed relationship between age and balance Fig.  was explSignificant associations were observed between age and hearing measures  are presented in Table As shown in Table For the left ear, PTA1, 500 Hz and 1000 Hz mediated the association between age and balance. Bootstrap results for these measures showed that the bootstrapped 95% CI around the indirect effect did not include zero (Path a*b). On the other hand, WIN 50% SNR, PTA2 and hearing thresholds of 2000 Hz, and 4000 Hz did not mediate the association between age and balance. Bootstrap results for these measures showed that the bootstrapped 95% CI around the indirect effect included zero.To determine whether the right or left ear was more likely to mediate the association between age and balance, we conducted a parallel mediation model in which both ears competed with each other as an explanatory mechanism. As presented in Table The results of the current study indicate a stronger contribution of the right ear to balance than the left ear. Consistently, the correlations between the right ear and balance were higher than those for the left ear. In the right ear, almost all the hearing measures mediated the relationship between age and balance . By contrast, in the left ear, only PTA 1 and hearing thresholds of 500 Hz/1000 Hz mediated this interaction. Hearing measures for the right ear evidenced a stronger mediation effect than the left ear with respect to the interaction between age and balance Tables , 5. Thes6. The right ear advantage is well-known for the processing of verbal stimuli, reflecting left hemispheric dominance for language6. Studies have argued for the enhanced role of the left hemisphere in the control of motor actions20. Although hemispheric function for postural control and balance is not fully understood, most studies indicate that the right cerebral hemisphere plays a more prominent role in the efferent processes responsible for balance control24. For example, Golomer et al.21 found that right hemispheric visual dominance is particularly useful for postural control in complex equilibrium conditions. On the other hand, Cioncoloni et al.25 suggested that the left hemisphere plays a critical role in the selection of the appropriate postural control strategy. These findings emphasize the fact that the cerebral role in postural control and the cortical mechanisms of spatial hearing are complex processes, and more research is needed to elucidate them26.To the best of our knowledge, this is the first study to suggest hemispheric lateralization and left hemisphere dominancy to account for the hearing-balance relationship. This should come as no surprise since all the major cognitive functions including language, spatial and emotional processing are lateralized12. The current findings suggest that frequencies within the speech range (500/1000/2000 Hz) are correlated with balance. Both PTA 1  which is the clinical predictor of the speech reception threshold (SRT), and WIN (speech perception in noise) in the right ear mediated the interaction between age and balance. These results raise the possibility that deterioration of speech perception in the presence of noise might indicate balance deterioration. However, pure tone thresholds of 4000 Hz, in both ears, were not correlated with balance and did not mediate the relationship between age and balance. Since age-related hearing loss is characterized by bilateral hearing loss above 2000 Hz, this strengthens the claim that the relationship between hearing and balance is affected by factors other than age-related hearing loss.Very little is known about the contribution of hearing at different frequencies to balance8, Criter & Gustavson14, Carpenter & Campos15, Li et al.27, Rumalla et al.28, Campos et al.29 and Doettl et al.30. Specifically, Lin and Ferrucci10 found that for every 10 dB increase in hearing loss, the probability of an individual reporting a fall increased by 1.4. The interaction between hearing and balance has also been reported in patients with hearing loss31. Impaired balance was also found to exist in younger populations with hearing impairments33. This association between hearing loss and falls may be accounted for by several mechanisms: (a) physiological mechanisms that may influence auditory and postural systems. These could involve a concomitant dysfunction of both cochlear and vestibular sensory organs given their shared location within the labyrinth in the inner ear, or age-related changes in the corpus callosum that could affect both hearing and walking34; (b) cognitive mechanisms such as paying attention to postural control might tap cognitive resources. Fewer cognitive resources and less attention due to hearing loss may impair postural balance in real life situations and increase the risk of falling36; (c) behavioral mechanisms such as hearing loss might influence spatial orientation, social parameters, and the interaction between the effects of reduced mobility and reduced auditory inputs. Hearing deterioration may thus restrict a person’s ability to monitor and perceive auditory environmental cues that provide spatial orientation8.The current study shows that hearing interacts significantly with balance in adults Table . This is38 the current study found a decline in hearing and balance with advancing age. Furthermore, the findings indicated that balance was correlated with hearing, even when controlling for age. As demonstrated in the current study, hearing mediated the interaction between age and balance. This implies that one of the reasons for the deterioration of balance with advancing age may result from hearing deterioration. This finding is supported by previous studies indicating that balance deterioration is positively correlated with the extent of hearing deterioration in hearing-impaired populations40.Consistent with previous studies41, in an attempt to better preserve the ecological validity of the human hearing-balance relationship. It is also important to note that since balance is a very complex function, the results of the balance test used in the current study (TUG) might have been affected by other factors such as peripheral hearing, vestibular, and visual factors. However, TUG is considered to be a good diagnostic tool for balance and risk of falling42, and is often being used in research evaluating balance in adult populations43. Further research should explore these topics in a variety of populations in different age groups and while using a variety of hearing/balance measures and pathologies.The current study used hearing tests that simulate everyday hearing situations (WIN), in addition to the commonly used index of hearing thresholds (pure tone thresholds in the range of 0.5–4.0 kHz). These tests were selected based on recommendations in previous studies44, in order to potentially reduce falling and prevent its consequences. The relatively greater contribution of the right ear to balance, compared to the left ear, should be considered during hearing evaluation and rehabilitation. Hearing may thus contribute to balance in addition to visual, vestibular, and proprioceptive input.Thus overall, the correlations between hearing and balance and the mediating effect of speech range frequencies on the age and balance relationship suggest that difficulties in understanding speech in adults over the age of 45y may indicate reduced balance and might imply the need for a balance evaluation. At the same time, balance difficulties may indicate the need for a hearing evaluation. Thus, the current study supports previous research recommending the evaluation of balance in individuals with hearing deteriorationA sample of 295 community dwelling adults  aged 46–75 years (58.5 ± 6.1), participated in this study. Written informed consent was obtained from all subjects. All participants underwent two hearing tests (Standard Pure-Tone Audiometry test and Words-in-Noise—WIN), one balance test (Timed Up and Go—TUG) and the Montreal Cognitive Assessment—MoCA. All methods were performed in accordance with the relevant guidelines and regulations.38, mobility using walking aids, and suspected presence of mild cognitive impairment as defined by the MoCA < 26/3045. After signing the informed consent form and completing the MoCA questionnaire, the participants were administered the hearing and the balance tests.Exclusion criteria included poor physical health47. To assess hearing thresholds, the Standard Pure-Tone Audiometry48 was administered at octave levels from 500 to 4000 Hz using a HARP mobile audiometer with TDH-50 earphones . The pure tone average 1 (PTA1) was calculated as the average hearing threshold at 500 Hz, 1000 Hz, and 2000 Hz. PTA1 is regarded as a predictor of the speech reception threshold. The pure tone average 2 (PTA2) was calculated as the average hearing threshold at 1000 Hz, 2000 Hz, and 4000 Hz. PTA2 emphasizes the weight of high frequencies to hearing.Hearing in the right and left ears was evaluated using Standard Pure-Tone Audiometry, and the Hebrew version of Words-in-Noise (HWIN) test46. The Hebrew version of the WIN consists of two lists of 35 common consonant–vowel-consonant (CVC) words mixed with 6 talkers’ babble at 7 signal- to- noise ratios (SNRs) from 24 to 0 dBSNR in 4 dB increments. The two lists were presented to each subject, one for each ear for open set identification47. The total number of correctly identified words and the 50% point in dBSNR (WIN 50% SNR) for each ear was calculated using the Spearman-Karber Eq. 49.The WIN is a word-recognition test to assess speech perception in noise53. The test requires the subject to stand up, walk 3 m, turn, walk back, and sit down. Time taken to complete the test is strongly correlated with level of balance and functional mobility. Cognition was assessed by the Hebrew version54 of the MoCA45.Performance-based balance was measured using the timed up and go test (TUG). The TUG is a widely used instrument that examines balance, functional mobility, and risk of falling across multiple adult populations41 Model 4 was used to calculate four sets of regressions . Pearson’s correlation analysis was used to determine the correlation between age, hearing tests and balance tests. A value of p < 0.05 was considered statistically significant. To examine the mediational role of the hearing measures, the PROCESS macroThis study was approved by the institutional review board for the protection of human subjects of Ono Academic College (201909ono).Supplementary Information.


More than half of high-risk neuroblastoma (NB) patients have experienced relapse due to the activation of chemoresistant minimal residual disease (MRD) even though they are treated by high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although MRD in high-risk NB patients can be evaluated by quantitative PCR with several sets of neuroblastoma-associated mRNAs (NB-mRNAs), the prognostic significance of MRD in PBSC grafts (PBSC-MRD) is unclear. In the present study, we collected 20 PBSC grafts from 20 high-risk NB patients and evaluated PBSC-MRD detected by droplet digital PCR (ddPCR) with 7NB-mRNAs . PBSC-MRD in 11 relapsed patients was significantly higher than that in 9 non-relapsed patients. Patients with a higher PBSC-MRD had a lower 3-year event-free survival (P = 0.0148). The present study suggests that PBSC-MRD detected by ddPCR with 7NB-mRNAs has a prognostic impact on high-risk NB patients. Neuroblastoma (NB); Minimal residual disease (MRD); Peripheral blood stem cell (PBSC); Neuroblastoma-associated mRNAs (NB-mRNAs); Droplet digital PCR (ddPCR). It originates from neural crest-derived sympathoadrenal progenitors , 2, 3 anTo identify MRD in NB patients, a set of neuroblastoma-associated mRNAs (NB-mRNAs) are commonly quantitated in bone marrow (BM), peripheral blood (PB), or PBSC samples due to the lack of recurrent genomic aberrations in NB cells , 13. SevBecause PB has no or fewer detectable tumor cells by immunocytology even when BM is positive in high-risk NB patients, there may be a reduced risk of contamination with tumor cells in PBSC grafts than in BM grafts . PBSC grAlthough we have shown that ddPCR-based MRD monitoring with 7NB-mRNAs  has a significant prognostic value for BM samples , it rema22.1Twenty high-risk NB patients according to the Children's Oncology Group (COG) Neuroblastoma Risk Stratification System , 28 or t2.27NB-mRNAs ddPCR assay was carried out as described previously , 19, 31.2.3The differences in the levels of 7NB-mRNAs between two sample populations were evaluated by the Mann–Whitney U-test. The prognostic value of the levels of 7NB-mRNAs was assessed using the receiver operator characteristic (ROC) analysis. The area under curve (AUC) was interpreted 0.50–0.69 as “low accuracy”, 0.70–0.89 as “moderate accuracy”, and “0.90–1.00” as high accuracy . EFS was33.1Twenty patients included in the present study were all high-risk patients. As summarized in 3.2To investigate the clinical significance of PBSC-MRD, we first determined the levels of each NB-mRNA  and 7NB-mRNAs by ddPCR in 20 PBSC grafts collected from 20 high-risk NB patients. Consistent with the results obtained from 208 BM and 67 PB samples , the lev3.3Although the level of 7NB-mRNAs in PBSC grafts was not so high as in BM and PB samples at diagnosis , it was 3.4To clarify the clinical significance of PBSC-MRD, we next performed survival analysis by plotting the Kaplan-Meier curve and estimated 3-year EFS and OS. In the entire cohort of 20 high-risk NB patients, 3-year EFS and OS was 45.0% (95% CI: 23.1–64.7%) and 69.3% (95% CI: 44.0–84.9%), respectively . Accordi4In the present study, we performed ddPCR-based PBSC-MRD monitoring in 20 PBSC grafts with 7NB-mRNAs and revealed that higher PBSC-MRD was significantly associated with poorer EFS in high-risk NB patients. To our knowledge, this is the first study to demonstrate a significant prognostic value of ddPCR-based PBSC-MRD for high-risk NB patients.A clinical significance of PBSC-MRD remained to be established for high-risk NB patients over the last decades. PBSC-MRD detected by qPCR with B4GALNT1, CHRNA3, DBH, DDC, PHOX2B, or TH mRNA was shown to be not statistically associated with outcome , 24, 26,Although NB cells present with very diverse phenotypes, recent studies explored the transcriptomic and epigenetic landscapes of NB cells together with neural crest (NC) cells and identified two super-enhancers (SEs) consisting of dense clusters of enhancers that underlay cell and lineage identity , 37, 38.In conclusion, we have revealed that PBSC-MRD detected by ddPCR with 7NB-mRNAs has a significant prognostic value for high-risk NB patients.Nanako Nino: Performed the experiments, Analyzed and interpreted the data, Contributed reagents, materials, analysis tools, or data, and Wrote the paper.Toshiaki Ishida; Akihiro Nishimura; Shotaro Inoue; Akihiro Tamura; Nobuyuki Yamamoto; Suguru Uemura; Atsuro Saito; Takeshi Mori: Contributed reagents, materials, analysis tools, or data.Kyaw San Lin; Kaung Htet Nay Win; Cho Yee Mon: Performed the experiments; Contributed reagents, materials, analysis tools, or data.Daiichiro Hasegawa; Yoshiyuki Kosaka; Kandai Nozu: Conceived and designed the experiments; Wrote the paper.Noriyuki Nishimura: Conceived and designed the experiments, Analyzed and interpreted the data, and Wrote the paper.Japan Society for the Promotion of Science [19K17331 & 21K07750].Dr. Suguru Uemura and Prof Noriyuki Nishimura were supported by Data included in article/supp. material/referenced in article.The authors declare the following conflict of interests: Noriyuki Nishimura received institutional research funding from Sysmex Corporation to Kobe University.No additional information is available for this paper.


Cisplatin is a critical component of first‐line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin‐induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy.Utilizing linear and logistic regression analyses on 1680 well‐characterized cisplatin‐treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities. Genome‐wide association studies and gene‐based analyses were performed on each phenotype.TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10−6) in gene‐based analysis. rs62283056 in WFS1 previously found to be significantly associated with hearing loss (n = 511), was marginally significant in an independent replication cohort . Gene‐based analyses identified significant associations between tinnitus and WNT8A (p = 2.5 × 10−6), encoding a signaling protein important in germ cell tumors.Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self‐reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork‐related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies.Genetics variants in  Cisplatin‐induced toxicities in testicular cancer survivors and their association with clinical characteristics  were evaluated along with the effect of modifiable factors  on risk of these toxicities. Genetic analysis identified genes that make certain individuals at risk for hearing loss or tinnitus after treatment with this drug. More than 5.8 million patients (pediatric and adults) globally are diagnosed each year with cancers  for which first‐line therapy can potentially include platinating agents.To ascertain both genetic risk factors and modifiable comorbidities for cisplatin‐induced toxicities, we constructed the Platinum Study, a well‐phenotyped cohort of testicular cancer survivors (TCS) treated with homogenous cisplatin‐based chemotherapy,WFS1  was associated with increased susceptibility to cisplatin‐induced hearing loss,p = 5.67 × 10−3).OTOS  was identified as marginally significant and functional studies in auditory cells indicated that knockdown of OTOS was associated with higher cellular sensitivity to cisplatin.Through an agnostic genome‐wide association study (GWAS), a single nucleotide polymorphism (SNP) in In the present study, we evaluated 1680 TCS from the Platinum Study to comprehensively investigate and quantify the extent to which nongenetic associations, including modifiable comorbidities  were related to all three neurotoxicities . To identify novel genetic signals associated with cisplatin‐induced hearing loss, tinnitus, and peripheral neuropathy, we performed GWAS in over 1000 survivors. We also attempted to replicate previously identified SNP associations for each phenotype.22.1All 1680 patients were enrolled in the Platinum Study, which includes eight cancer centers in the United States, Canada, and United Kingdom.2.2Patient data were determined at clinical follow‐up or collected from medical records following a standardized protocol as previously described.Information regarding hypertension, hypercholesterolemia, persistent dizziness/vertigo, overall health conditions, noise exposure, alcohol consumption, and tobacco use were also obtained from these questionnaires as previously described .11, 12.3n = 1258; previous study analyzed 488 subjects of this cohortCisplatin‐induced hearing loss was modeled as a quantitative phenotype using the geometric mean of bilateral average air conduction thresholds measured at frequencies between 4 and12 kHz as described previously . Survivors receiving >300 and < 400 mg/m2 cumulative cisplatin dose were excluded due to small sample size (n = 69). In addition, the majority of TCSs receive typical homogeneous treatments with cumulative cisplatin dose of 300 or 400 mg/m2. We further performed a two‐proportion z‐test for each phenotype, comparing the proportion of survivors with the phenotype. For cisplatin‐induced hearing loss, the two‐proportion z‐test was applied on patient proportions with hearing threshold >20 and ≤20 dB; for tinnitus, the population proportions of the case and control were compared; and the proportion of patients with severe cisplatin‐induced peripheral neuropathy was compared to the proportion of the remaining cohort.To investigate cumulative cisplatin dose threshold, regression analyses were also conducted adjusting for age at clinical examination for each phenotype with cumulative cisplatin dose as a categorical variable  at Regeneron Pharmaceuticals. Sample‐level and SNP‐level quality control criteria were consistent with our previous studiesexcluded .2.6p < 0.0001; outside of work: OR = 2.2, 95% CI = 1.6–3.0, p < 0.0001; both at work and outside of work: OR = 1.5, 95% CI = 1.2–1.8, p < 0.0001; Figure p < 5 × 10−8.All GWAS were conducted using methodology similar to previous studies,−6. After collecting the candidate genes that were genome‐wide significant or nearly significant, we extracted SNPs with a GWAS p < 1 × 10−5 and within 25 kb upstream or downstream of these genes. We then searched these SNPs in GTEx portal for splicing quantitative trait loci (QTL) or expression QTLs without specifying tissue types, but associated with the candidate genes.For the gene‐based association analysis, the aggregated effect of all SNPs within a gene was analyzed simultaneously in the functional mapping and annotation of GWAS (FUMA) platform using the multi‐marker analysis of genomic annotation (MAGMA) method that is based on a multiple regression model that efficiently incorporates linkage disequilibrium between SNPs.2.7WFS1 for hearing lossOTOS for tinnitus.n = 606) and tinnitus (n = 325), respectively. The covariates were consistent with the original GWAS analysis, and the significance threshold is 0.05.Using independent cohorts, we evaluated two SNPs previously associated with cisplatin‐induced neurotoxicities: rs62283056 in 2.8Gene expression data for two genes  from the FUMA gene‐based analysis in central nervous system (CNS) was acquired from the Cancer Cell Line Encyclopedia.33.12. Most survivors were treated with bleomycin, etoposide, and cisplatin  or etoposide and cisplatin . 46.5% of survivors received <400 mg/m2 cumulative cisplatin dose, and 53.5% of survivors were treated with ≥400 mg/m2.Cohort characteristics stratified by each cisplatin‐induced phenotype, hearing loss, tinnitus, and peripheral neuropathy are provided in Table 3.2p < 0.0001). Hearing loss was positively correlated with tinnitus  and peripheral neuropathy . Risk of tinnitus was 3.9‐fold (95% CI = 3.0–5.1) and 2.7‐fold (95% CI = 2.1–3.3) greater for survivors with more severe hearing loss and peripheral neuropathy, respectively. Similar associations were observed for peripheral neuropathy .Cisplatin‐induced hearing loss, tinnitus, and peripheral neuropathy were interdependent, adjusting for age and cumulative cisplatin dose . Hypertension , BMI at evaluation , and nonwork‐related noise exposure  were positively associated with hearing loss. However, hearing loss was not associated with persistent vertigo, hypercholesterolemia, smoking status, excess alcohol, work‐related or both types of noise exposure . Tinnitus was positively correlated with persistent vertigo , hypertension  and hypercholesterolemia . We also observed positive associations between tinnitus and chronic smoking , current smoking , and noise exposure . However, no association was observed between tinnitus and ever smoking, excess alcohol consumption, or BMI at clinical evaluation . Persistent vertigo  and hypertension  were positively associated with peripheral neuropathy. Risk of peripheral neuropathy was also positively associated with smoking status  and excess alcohol consumption . BMI at evaluation was marginally significantly associated with peripheral neuropathy , but no association was found between peripheral neuropathy and hypercholesterolemia ; a stronger increase of risk was found between 400 mg/m2‐treated‐TCS and >400 mg/m2‐treated‐TCS  compared with those receiving 400 mg/m2  with no significant differences for <300 mg/m2 versus 300 mg/m2 and 400 mg/m2 versus >400 mg/m2 . Although proportions of survivors with hearing loss treated with 400 mg/m2 and 300 mg/m2 were not significantly different, significant proportional differences were observed comparing survivors with peripheral neuropathy .To further confirm the dose threshold of cisplatin‐induced neurotoxicities, two‐proportion 3.73.7.1TXNRD1 was nearly genome‐wide significant for the gene‐based analysis  and TXNRD1 expression in CNS tumor cell lines, yet no other significant relationships were observed TXNRD1 was borderline significant with a p‐value of 5.7 × 10−6. This intronic variant is a sQTL that regulates alternative splicing of TXNRD1 in skeletal muscle as reported by the GTEx Portal.In a GWAS of hearing loss for 1071 TCS, no SNP met genome‐wide significance ; however3.7.2WNT8A as genome‐wide significant (p = 2.5 × 10−6).There were 979 (59.6%), 426 (25.9%), 118 (7.2%), and 120 (7.3%) survivors reporting none, mild, moderate, and severe tinnitus, respectively. After removing survivors who reported mild tinnitus, subjects were then dichotomized to 979 (80.4%) controls (none) and 238 (19.6%) cases (moderate/severe). No SNPs met genome‐wide significance in the GWAS of tinnitus Figure ; however3.7.3Of the 1653 TCS, 704 (42.6%) reported no peripheral neuropathy, 740 (44.8%) reported mild peripheral neuropathy, and 209 (12.6%) reported severe peripheral neuropathy. GWAS was performed on 1397 survivors. Neither the SNP‐based nor gene‐based analysis of peripheral neuropathy identified significant signals Figure .3.8WFS1 was borderline significant (p = 0.06). The overall hearing threshold distributions did not differ between discovery and replication cohorts . No association (p = 0.7) was observed between tinnitus and rs7606353 in OTOS  above 400 mg/m2 compared to 400 mg/m2. In addition, gene‐based association analysis identified WNT8A significantly associated with tinnitus.Based on the largest study to date of cisplatin‐induced neurotoxicities, we demonstrate that a substantial proportion of TCS treated with cisplatin‐based chemotherapy experience hearing loss, tinnitus, and peripheral neuropathy, and those that do experience neurotoxicities were more likely to have hypertension and describe their health as poor. Hearing loss, but not tinnitus or periperhal neuropathy, was associated with survivors with greater BMI. Conversely, tinnitus and peripheral neuropathy, but not hearing loss, was associated with persistent vertigo or dizziness. Similar results were observed in evaluating modifiable risk factors demonstrating survivors who are either chronic or current smokers are more likely to experience tinnitus or peripheral neuropathy, but not hearing loss. We identified a marked increase in risk for peripheral neuropathy (1.3‐fold) and significantly more hearing loss when comparing 300 mg/m4.1WNT8A to be genome‐wide significant for tinnitus and TXNRD1 as having borderline genome‐wide significance for hearing loss following cisplatin treatment through a gene‐based association analysis. Human WNT8A mRNA is expressed in NT2 cells with neuronal differentiation potentialWNT8A plays a key role in the Wnt/β‐catenin signaling pathway, inducing cell proliferation in a variety of cancer types, including colorectal cancer, pancreatic cancer, and gastric cancer. Wnt8a (mouse homolog) is expressed in the hindbrain and is involved in early inner ear development in mice.Wnt8a and Txnrd1 are expressed in mouse cochlea.Txnrd1 gene in the auditory portion of the inner ear and cochlea.For the first time, we identified 4.2The association between tinnitus and persistent dizziness/vertigo in our cisplatin‐treated TCS has also been shown for de novo tinnitus, as inner ear problems are strongly implicated in balance disorders, including vertigo.4.3We observed greater risk of both tinnitus and peripheral neuropathy for chronic smokers and current smokers. Tobacco use is known to be associated with poorer response to cancer treatments, increased cancer mortality, and risk of second primary cancer.2 cisplatin, respectively although occasional patients may receive doses of cisplatin greater than 400 mg/m2. Our study evaluated the risk of toxicity at these cumulative doses to provide physicians valuable information to make an informed decision since both BEPX3 and EPX4 are considered curative for testicular cancer.β = 0.4) or tinnitus (3.1‐fold) following >400 mg/m2 cumulative cisplatin versus 400 mg/m2. A previous study showed that patients treated with >400 mg/m2 cumulative cisplatin dose were 2.6‐fold more susceptible to tinnitus than those treated with ≤400 mg/m2Cisplatin‐based therapy consists primarily of either three cycles of BEP or four cycles of EP resulting in a cumulative dose of 300 or 400 mg/m2 cumulative cisplatin dose with 400 mg/m2 (1.3‐fold). Consistent with our results, previous studies suggest that significant peripheral neuropathy occurs when cumulative cisplatin dose exceeds 300–400 mg/m2.2 cisplatin; and the conduction velocities of SNAP were reduced 10%–15% for survivors treated with cumulative doses of 400–700 mg/m2 cisplatin compared to patients treated with <300 mg/m2. Among 80 women with recurrent ovarian cancer, Van den Bent and colleagues2 cumulative cisplatin dose compared to 300–420 mg/m2. After a cumulative cisplatin dose of 600 mg/m2, all patients (n = 80) developed some degree of peripheral neuropathy with 30%–40% of patients having moderate sensory neuropathy, and 10% having severe and disabling neuropathy. Taken together, these prior reportsWe identified a marked increase in risk for peripheral neuropathy when comparing 300 mg/mWFS1 was significantly (p = 1.4 × 10−8) associated with hearing loss,OTOS likely due to small sample size of the replication cohort (n = 325). In addition, the MAF (0.032) was lower than that of 0.04 in the previous study . The definition of loud noise exposure is another limitation, as the participants self‐reported their exposure, and details with regard to noise duration, loudness, or frequency (or timing in relationship to chemotherapy) was not queried. In addition, teasing out whether hearing loss is due to cisplatin, noise exposure or the combination is a challenge. Furthermore, when analyzing the effect of cumulative cisplatin dose on toxicity, the sample size for <300 and >400 mg/m4.5Our findings emphasize the importance of clinical characteristics associated with cisplatin‐induced neurotoxicities. Clinicians should ensure that patients are aware of these iatrogenic toxicities and their associated comorbidities, including hypertension and hypercholesterolemia. Associated clinical conditions and behavioral characteristics should be addressed before receiving cisplatin‐based chemotherapy, such as recommending close monitoring of blood pressure and cholesterol level, and encourage smoking cessation.2 may result in disproportionally more survivors with ototoxicity than groups receiving lower doses. As noted previously, follow‐up hearing assessment guidelines exist for children given cisplatin‐based chemotherapy; however, no similar recommendations have been developed for adult‐onset cancer survivors.2 against 400 mg/m2 cumulative cisplatin dose suggests for some patients , a physician might consider the BEPX3 regimen over the EPX4 regimen. Additional research efforts are needed to replicate and validate the genetic risk factors, and their potential for new drug development to either prevent or treat these long‐lasting neurotoxicities. Further implementation of individualized risk assessments to identify patients a priori who are more susceptible to developing neurotoxicities, thus allowing for personalized education, counseling, treatment, and monitoring plans, are needed.In addition, clinicians should be aware that a cumulative cisplatin dose of >400 mg/mStudy procedures were approved by each institution's Human Subject Review Board and conducted in accordance with the U.S. Common Rule. All participants provided written consent for study participation, access to medical records, and genotyping.DataS1Click here for additional data file.


According to the IBGE, Brazil had 21 million elderly persons in 2008.To study the effects of speech therapy - fitting of hearing aids - on the quality of life of elderly persons and restriction of participation according to sex and age.50 elderly subjects, 23 females and 27 males, were allocated to Group 1 and Group 2, and were assessed with questionnaires (HHIE and SF 36) before and one year after fitting hearing aids; subjects were monitored every two months.The HHIE Social and Emotional Scale was significant with regards to sex and age after fitting hearing aids. The SF 36 results after fitting hearing aids were significant in six of eight test aspects. Two test aspects were not significant after fitting hearing aids; pain, however, was significant in the elderly group 2.There is little awareness of participation restrictions after the HHIE intervention. There is improvement in quality of life after rehabilitation. Retrospective study. One of the most devastating and incapacitating deficiencies of old age is presbiacusis. Hearing loss causes difficulties in understanding speech, affects communication, and compromises family and social life. Thus, auditory loss in the elderly affects not only hearing but also has marked psychosocial implicationsAccording to the Pan-American Health Organization (PAHO), healthy and active aging implies valuing autonomy and preserving physical and psychic autonomy, among other factors, and preventing functional losses or reducing their negative effectsIn the Brazilian Unified Health System , it is considered essential to assure full care to the elderly population and to emphasize healthy and active aging . It is thus necessary to learn about the Brazilian elderly population; according to the Brazilian Geography and Statistical Institute  there are nearly 21 million elderly people in BrazilThe national policy for the elderly aims to assure social rights for this population group by promoting autonomy and effective participation in society with the purpose of maintaining quality of life. According to the IBGE, if the fertility and longevity trends continue in Brazil, the number of elderly people is estimated to be over 30 million in the next 20 years, which comprises nearly 13% of the population.Living longer may imply in a life of physical incapacity and dependence. There is a further challenge for healthcare professionals working with elderly people: to assess quality of life rather than only to measure aging, and the impact of treatments and public policies for this age groupIn this context, healthcare professionals need to specifically study this age group. Questionnaires have been used as evaluation tools to measure the difficulties of elderly individuals and their perception of these handicaps. One of these questionnaires is the Hearing Handicap Inventory for the Elderly; it aims to assess the impact of hearing loss on the emotional and social realities of elderly subjects. Another such questionnaire is the Short Form Health Survey - SF 36, which aims to assess health and quality of life; it consists of two parts: the first investigates the health status  and the second evaluates the impact of disease on the patient's daily life.A few questions were subsequently raised: what is the impact of hearing loss on the quality of life of elderly individuals? Do men or women have more perception of restrictions in daily life? Which age group has the most compromised quality of life?It is evident that a protocol for assessing the quality of life of elderly individuals and their opinion about issues they consider important is needed.Therefore, the purpose of this study was to investigate the effects of phonoaudiological interventions (fitting hearing aids) in relation to restricted participation in daily life activities and quality of life of elderly individuals; the variables were sex and age.The institutional review board assessed and approved the study design (no. CEP 0913/08). Patients that agreed to participate signed a free informed consent form (based on the Resolution 196/96 on guidelines about research in human beings).The following inclusion criteria were defined: age over 60 years, up to severe bilateral symmetrical sensorineural hearing loss, speech recognition score over 50%, indication for adapting binaural hearing aids, no evidence of other conditions, and being literate.The sample comprised 50 elderly subjects - 23 female (46%) and 27 male (54%) - aged 60 years or above. The subjects were allocated to two age groups, as follows: Group 1 (G1), which consisted of 24 subjects (48%) aged from 60 to 74 years, of which 11 were female and 13 were male, and Group 2 (G2), which consisted of 26 subjects (52%) aged 75 years and above, of which 12 were female and 14 were male.Audiological testing consisted of pure tone audiometry, play audiometry, and immittance testing, which were done at our Clinic by expert staff speech therapists.The self-assessment questionnaires used in this study were the Hearing Handicap Inventory for the Elderly (HHIE) and the Medical Outcome Study 36-Item Short Form Health Survey (SF 36).The HHIE questionnaire was developed to assess the psychosocial, emotional, and social consequences of hearing loss in elderly patients. It was originally developed in English language and adapted to Portuguese by Wieselberg (1997). We used the pencil and paper application technique.The HHIE consists of 25 questions, of which 13 explore the emotional and 12 the social/situational consequences of hearing loss. Restrictions to participate are classified according to a scoring system in which four points are given to the answer “yes”, two points to the answer “sometimes”, and zero points to the answer “no”. A higher score means that an individual is more aware of his restrictions to participate - hearing loss imposes more auditory and non-auditory difficulties. The scores are distributed as follows: no perception of a handicap = 0 to 16; mild to moderate perception of a handicap = 18 to 42; and severe/significant perception of a handicap = > 42 points.The Medical Outcome Study 36-Item Short Form Health Survey (SF 36) was first developed and then translated for the Brazilian populationEight aspects were evaluated, as follows: functional capacity - 10 items; physical aspects and vitality - four items; emotional aspects - three items; pain and social aspects - two aspects; general health status and mental health - five items. Each subject is scored in each aspect, which is then consolidated in a 0 to 100 scale where 0 is the worst score and 100 is the best; thus, higher scores indicate better quality of life.Seven meetings with two-month intervals between each were scheduled to monitor the patients as they adapted to hearing aids. During these meetings patients were oriented about the use, care, and handling of hearing aids, as well as communication strategies.st meeting - The elderly subjects answered the printed SF 36 and HHIE questionnaires. After this meeting and during August 2008, retroauricular bilateral hearing aids were fitted; all were of the same brand and type, and had been selected beforehand by the institution staff.1nd meeting - Elderly subjects at this point were adapted to their hearing aids and could clear up any doubts about their use, handling, and care. In this meeting, each subject was given the opportunity to describe his or her difficulties and victories with using hearing aids up to this point.2rd meeting - Subjects were given instructions about how to use telephones. Doubts about handling and care of hearing aids were discussed.3th meeting - In this meeting each subject was given a dehumidifier and a device for cleaning the molds. Verbal and practical instructions were given about how to use these materials, and an explanatory folder was also handed out.4th meeting - Elderly subjects now have used the hearing aids for over six months; but instructions about their use, care, and handling were repeated. The group could be seen to interact; those that had adapted better helped other with difficulties.5th meeting - Each subject was given a key ring that tested the hearing aid battery; verbal and practical instructions about how to use this device were given; an explanatory folder was also handed out.6th meeting - In this last meeting, after about one year of bilateral hearing aid use, all elderly subjects were answered the SF 36 and HHIE questionnaires.7The sample was characterized according to sex and age. Tables containing descriptive statistical values for the HHIE and SF 36 scores were made for each period, sex, and age group.Analysis of variance with repeated measures was applied to compare the mean scores of questionnaires , sex, and age groupsThe statistics software Minitab version 15 and the SPSS version 11 were used in the statistical analysis. The significance level for each hypothesis was 0.05, and the significant p-values were marked with an asterisk (*).The study sample comprised 50 elderly subjects, 23 female (46%) and 27 male (54%). There were 24 subjects aged from 60 to 74 years (48%) and 26 subjects aged over 75 years (52%).Descriptive statistics were made for the HHIE questionnaire scores before (pre) and after (post) the intervention .Table 1DThe increasing elderly population in Brazil requires healthcare programs to provide adequate quality of life for this age group.The impact of auditory loss on the quality of life of individuals may be measured by the configuration and degree of hearing loss, as well as the age of patients when this condition arises. Thus, decreased participation in activities of daily life due to hearing loss compromises social and professional performance, and therefore quality of life.The mean values of the total HHIE score were 32.9% (pre-intervention) and 8.8% (post-intervention), which was a significant improvement. These results are compatible with the self-awareness of moderate participation restriction in the pre-adaptation period and non-awareness in the post-adaptation period.Authors in several studies that applied the HHIE questionnaire have reported that elderly individuals need to be included in hearing rehabilitation programs to minimize the psychosocial reactions to hearing loss. These authors have also found that elderly subjects show effectively fewer restrictions to participation after taking part in hearing rehabilitation programs. The importance of hearing aid fitting is also underlinedA separate analysis of the emotional and social/situational scores revealed that the mean post-intervention (one year later) scores of the emotional scale were significantly lower than pre-intervention scores in both age groups (60 to 74 years and 75 years or more) in both males and females.The mean score in elderly male subjects was significantly higher in the pre-intervention period compared to females; this difference in means disappeared in the post-intervention period. The decrease between the pre-and post-intervention period was larger in males than in females, which showed that elderly male subjects perceived more their restrictions to participation before the intervention.The mean post-intervention score in the emotional scale was significantly lower compared to the pre-intervention period in the two age groups (60 to 74 years and 75 years or more). The mean decrease between the pre- and post-intervention periods was larger in elderly subjects aged 75 years or more, showing that this group perceived better their restrictions before the intervention, and therefore benefitted more from it.The mean scores in the social/situational scale in both periods were significant; they were lower after the intervention in males and females. The mean scores in elderly male subjects were higher compared to females. Thus, the mean decrease between the pre- and post-intervention periods was significantly higher in males, who once again perceived more their restrictions to participation, and therefore benefitted more after the phonological intervention.Other studies have shown that elderly males perceive more their restrictions than elderly females, which is similar to our findings in the present study.It is thought that elderly males have a better perception of their restrictions because this group - culturally in our society - is often the family provider even when aged; thus, restrictions to participation are perceived as a handicap.A few authors have found that benefits of hearing aids use may be evaluated after six months of effective use.It is thought that adaptation time could have an influence on benefits; the reevaluation interval in the present study was one year, which was considered sufficient time to reapply the questionnaire.Our findings showed that self-awareness of restrictions to participation in elderly subjects decreases after one year of hearing aid use. Such improvement may be attributed only to hearing aid fitting, as reported in several papers. On the other hand, it is important to underline that we monitored our subjects every two months in meetings in which they were able to clear their doubts about hearing aids, receive instructions about communication strategies, and mainly generate affective bonds - a relationship of trust - with the researcher. This procedure undoubtedly influenced the positive outcome of this study.Among the results of the SF 36 questionnaire, in which higher scores equate with better quality of life, the mean functional ability scores after the intervention were significantly higher irrespective of sex and age, compared to the pre-intervention period.It should be pointed out that the number (N) of elderly subjects was about half of the total N (50) when the analyses were made according to the variables sex and age group. This reduction may have contributed to the observed lack of significance.The SF 36 questionnaire showed that the highest number of clinical correlations and statistically significant results among the data was found in the functional ability aspectThe mean physical aspect scores after the intervention were significantly higher compared to the pre-intervention scores. Our analysis showed that the activities included in the physical aspect improved significantly in the context of general data; they were not affected by the variables sex and age group. This was also observed in the functional ability aspect.The worse scores in a study that applied the WHOQOL-bref questionnaire were found in the physical domain irrespective of sex. The authors concluded that there were no relationships between hearing loss and the quality of life of elderly subjects in their sample. They found a correlation between age and social relationships, in which more advanced age correlated with less participation in social activitiesThe lowest scores in the present study were found in the physical aspect, which was associated with the ability of subjects to perform physical activities such as climbing stairs, walking, and carrying out household chores.The results of the pain aspect revealed no differences in the mean scores before and after the intervention, irrespective of sex and age group. The mean scores for the age group aged 75 years or more were significantly higher, showing that their quality of life was better compared to the 60 to 74 year age group irrespective of sex and pre-and post-intervention periods. The elderly subjects in the more advanced age group were more active; their energy and well-being were probably the result of better physical status and less pain, which could explain these findings.The results according to age revealed that subjects at more advanced age had the best scores. According to the authors, this showed that older subjects had a better quality of life. These results also showed that the SF 36 questionnaire was an adequate tool for assessing the quality of life of retired individuals in the studyThe mean pre- and post-intervention scores of the general health status did not differ; these results were independent of sex and age group. This was expected, as elderly subjects are undergoing a natural aging process.The results of the physical aspect, pain, and general health status were the worst. In the variable sex, male elderly subjects had better scores in nearly all aspects except for general health status and emotional aspect. In our study, elderly female subjects considered their health worse compared to elderly male subjectsThe vitality aspect scores were significantly higher in the post-intervention period compared to the pre-intervention period irrespective of sex and age group. This is evidence that effective hearing aid use helped improve the quality of life, which was evidenced as better vitality. How do we explain increased vitality associated with hearing amplification? Amplification may foster interaction and better communication, which translates into more energy for activities of daily life.The elderly subjects performed better in the social aspect after the intervention. The mean post-intervention scores were significantly higher than before the intervention; this result was independent of sex. The difference in mean scores before and after the intervention was age-dependent; it was significantly higher in the 60 to 74 year age group. In the 75 year age group there were no differences in the means of both periods.Several studies have investigated the relationship between hearing loss and quality of life by using the WHOQOL-bref self-assessment tool; the physical, psychological, social and environmental relationships were assessed. The best scores were seen in the social relationship domain. This was a surprise for researchers, who thought that aging would be a time for social withdrawal, and that the elderly subjects presented hearing lossThe mean emotional aspect scores were significantly higher after the intervention compared to the pre-intervention period irrespective of sex and age group. Our results showed that the mean score was higher in females aged 75 years or more compared to those aged 60 to 74 years; this result indicated that females are more sensitive to emotional issues. There were no age-related differences in self-awareness of quality of life among male subjects.Effective use of hearing aids improved communication, which made it possible for elderly individuals to reassume their family and social interactions, thereby improving their quality of life. The author found that the quality of life improved after hearing aids were fitted, especially in the psychological domain, which underlines the importance of hearing - and interventions on hearing - for quality of life and general health in the elderly. The results in the psychological domain improved significantly in both males and females; thus, the variable sex did not affect the resultsThe emotional aspect scored low in the present study; the worse results were seen in elderly females, indicating that these individuals were more susceptible to emotional issues.The mean scores for the mental health aspect were significantly higher after the intervention compared to the pre-intervention period irrespective of sex and age group.The mean scores in the post-intervention period were higher than in the pre-intervention period in six of eight aspects in the general population , which shows that quality of life improved after the phonoaudiological intervention. Sex and age group differences were in general not seen, which may be explained by the small sample size. On the other hand, analysis of the quality of life by the SF 36 showed that this type of study is relevant for elderly subjects with hearing loss; although it did not include specific questions on communication and hearing, it was sensitive enough to identify an improvement in the quality of life because of amplification. Only two of eight aspects did not improve after one year of hearing aid use and monitoring, namely pain and general health status. This may be explained by the fact that elderly persons experience a chronic condition that gradually restricts their activities of daily life. The aspect vitality improved significantly after one year of hearing aid amplification. This improvement may be attributed to an increased will to participate in activities, as elderly individuals feel safer and become more confident simply by being able to listen and understand speech.Because the study sample comprised elderly aging subjects with hearing loss and some degree of awareness of their restrictions, the results were both important and expected. The subjects underwent a phonoaudiological intervention - fitting hearing aids - and were monitored during one year.In the present study, the assessment protocol consisted of self-assessment questionnaires; the results showed that these questionnaires adequately measured changes in quality of life and restrictions to participation in daily life. The HHIE questionnaire, which specifically evaluates hearing, has been used frequently by researchers in this area of study. We found no references in the literature about the use of the SF 36 questionnaire - which evaluates health in general - for assessing the quality of life of individuals with hearing loss. Thus, the results were both surprising and expected; it was possible to measure quality of life improvements and a reduction in restrictions to participation because of a phonoaudiological intervention.A critical analysis of the results yielded the following conclusions: there is less self-awareness of restrictions to participation after the phonoaudiological intervention in the social and emotional scales in the HHIE questionnaire. Elderly male subjects were more self-aware of restrictions to participation in the emotional and social scales before the phonological intervention. Elderly subjects in the older age group were more self-aware about restrictions to participation in the emotional scale before the phonoaudiological intervention.The quality of life was shown to improve after the phonoaudiological intervention in the functional ability, physical ability, vitality, emotional, social, and mental health aspects of the SF36 questionnaire irrespective of sex and age.