- Email: [email protected]
Hearing handicap in Asian patients with dementia
Am J Otolaryngol xxx (xxxx) xxxx
Contents lists available at ScienceDirect
Am J Otolaryngol journal homepage: www.elsevier.com/locate/amjoto
Hearing handicap in Asian patients with dementia Bibek Gyanwalia,b, Saima Hilala,b,c,g, Narayanaswamy Venketasubramaniand, ⁎ Christopher Chena,b, Jenny Hooi Yin Looe,f, a
Memory Aging & Cognition Centre, National University Health System, Singapore Department of Pharmacology, National University of Singapore, Singapore Departments of Epidemiology and Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands d Raffles Neuroscience Centre, Raffles Hospital, Singapore e Department of Otolaryngology, Head and Neck Surgery, National University Hospital, Singapore f Department of Otolaryngology, Head and Neck Surgery, National University Singapore, Singapore g Saw Swee Hock School of Public Health, National University of Singapore, Singapore b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Dementia Hearing handicap Hearing loss Memory clinic
Background: Hearing loss and hearing handicap may contribute to cognitive impairment and dementia. The purpose of this study was to analyze the association between hearing loss and hearing handicap with dementia in an Asian memory clinic parents. Methods: This study includes the data obtained from patients with mild dementia who attended the National University hospital memory clinic and non-demented healthy subjects among spouses and caregivers who are non-genetically related to our patients. All participants underwent comprehensive physical, medical, neuropsychological and audiological assessments (i.e. pure tone audiometry - PTA). Disabling hearing loss was defined as a hearing loss of > 40 dB in the better ear on PTA. Amsterdam Inventory for Auditory Disability and Handicap (AIADH) questionnaire was administered through the verbal interview to measure their hearing handicap score. Linear regression models were used to investigate the association between hearing loss and hearing handicap with dementia. Mean differences (β) with 95% confidence intervals (CI) were calculated. Results: 91 participants (65–90 years old) were recruited for this study; 39 of them were patients with dementia and 52 were non-demented healthy controls. 48.7% of the patients with dementia had disabling hearing loss, which is higher than the non-demented controls (25.0%) (p = 0.019). The significant association between hearing handicap (as measured by AIADH) and dementia was observed, which was independent of demographic factors and audiology related history and PTA average (β = −6.40; 95% CI =0.11.99, −0.81, p = 0.025). There was no independent association between hearing loss and dementia (p > 0.05). Conclusion: A significant association between hearing handicap and dementia was found. The mechanism of this association requires further research and may involve higher order central processing disorder.
1. Introduction Dementia has become one of the most important public health concerns [1]. In 2017 the World Health Organization (WHO) estimated that 50 million people worldwide are living with dementia, which is expected to triple by 2050 [2]. Dementia is a chronic progressive syndrome characterized by loss of cognitive functions [2]. In addition to loss of cognitive functions, dementia can also affect perception senses [3,4]. Among them auditory sense is most commonly affected, which manifests as hearing loss [3,4]. Interestingly, hearing loss is one of the most common sensory deficits in the elderly [5]. In 2018, WHO reported that 6.1% of global population had hearing loss, and one- third ⁎
of them were the elderly [6]. Approximately 50% of those cases with hearing loss occur in low economic countries in Asia and Africa, which show an uneven distribution of disease burden across the region [6]. Hearing loss typically begins by affecting the perception of high frequencies sound, which compromise speech understanding comprehension and communication [7]. Furthermore, elderly subjects with hearing loss experiences difficulty in distinction, localization and detection of sound, which may affect their everyday listening [8]. In this way, hearing loss thus, has significant psychological, physical, social and cognitive consequences [9]. Hearing loss is considered as one of the modified risk factor of dementia [9]. Hearing loss can be modified by the use of hearing aid and
Corresponding author at: National University Hospital Medical Centre, Level 15, ENT, Head & Neck Surgery Clinic, Singapore 119074, Singapore. E-mail address: [email protected] (J.H.Y. Loo).
https://doi.org/10.1016/j.amjoto.2019.102377 Received 31 October 2019 0196-0709/ © 2019 Published by Elsevier Inc.
Please cite this article as: Bibek Gyanwali, et al., Am J Otolaryngol, https://doi.org/10.1016/j.amjoto.2019.102377
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
as mild dementia [Global Clinical Dementia Rating (CDR) Score = 1)]. Controls were defined as patients who were cognitively normal on objective neuropsychological assessments and with no functional loss and were classified as non-demented subjects. 39 subjects with mild dementia as clinical convenience sample were recruited from the memory clinic at the National University Hospital, while 52 healthy non-demented subjects were recruited among spouse or caregivers of patients who were not genetically related to our patients. All the subjects underwent comprehensive physical, medical, neuropsychological [which included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA) and CDR interview] and audiological assessments. Assessments were made in a single session which lasted for approximately 1 h. Breaks were introduced if subjects felt tired. None of our subjects were previous and current users of hearing aid or had any hearing implants. Hearing amplification device was not used during the clinical and audiological assessments. Written consent was obtained for each participant prior to the procedures. This study was approved by the National Health Group (Domain D) ethics board with reference number DSRB Ref: 2011/ 01610.
other hearing assistive devices [10]. A recent study by Livingston et al. suggested that mid-life hearing loss is responsible for 9% of dementia cases [11]. In 1996 Gold et al. reported that > 90% of elderly patients with dementia had hearing loss [12]. Moreover, the prevalence reported in this study is probably higher than general age matched population. Another study conducted in Brazilian and American elderly patients with cognitive impairment reported the prevalence of hearing impairment as 68.9% and 60% respectively [13,14]. Prevalence of dementia and hearing loss differs in different studies, which is not surprising given the different genetic composition, risk factors, and environmental exposure in different ethnicities [15–17]. While these studies indicate different prevalence rate across population hence these studies need to be validated with more recent data and across different population such as in Asia. In Asian countries such as Japan, Korea, China and Singapore with the increasing number of elderly population, a higher number of parents with dementia and hearing loss are expected, which will increase the socio-economic and healthcare burden of the country [18]. Singapore is one of the countries in Asia with the most rapidly aging population [18] A study conducted by Lee et al. in a community-based population reported that > 22% of elderly above 65 years old had hearing loss [19]. This problem will grow even more serious given that the number of elderly Singaporeans above 65 years is expected to double from 1 in 8 in 2015 to 1 in 4 in 2030 [18]. Similarly, recent statistics from the Alzheimer's Disease Association predicts an exponential increase in patients with dementia in Singapore from 53,000 dementia patients by 2020, to more than triple to 187,000 by 2050 [20]. This situation is also similar in other Asian countries, thus there is need to investigate the association between hearing loss and dementia and its preventive measures. In investigating the association between hearing loss and dementia previous studies reported significant association between poor hearing dementia [21–24] whereas others did not [7,25,26]. None of these studies reported on the additional handicaping effect of hearing loss in elderly with dementia in their everyday life. In patients with dementia, cognitive impairment and hearing impairment have synergistic effect manifesting as hearing handicap [27,28]. It has been shown that selfreported hearing disability measured by Amsterdam Inventory for Auditory Disability and Handicap (AIADH) is of the appropriate test batteries to measure hearing handicap [27–29]. A simple screening questionnaire such as AIADH would help the memory clinic physician to evaluate the hearing handicapping effect in patients with dementia. To date, no guidelines are provided to mandate hearing screening as part of the routine neurocognitive assessment for patients with cognitive impairment. Therefore, it remains uncertain how many patients diagnosed with dementia in memory clinics also present with hearing loss or hearing handicap, Moreover, the influence of hearing impairment on diagnosis of dementia is still unknown. Hence, it is still unclear if hearing loss or hearing handicap can be considered as a risk factor for dementia. In view of these gaps, we hypothesized that: [1] more number of patients with dementia has hearing loss and hearing handicap compared to non-demented subjects in memory clinic and [2] hearing loss and hearing handicap are associated with dementia. In this study we aim to study the establish the baseline hearing profile of patients with dementia seen at National University Hospital, Memory Clinic and their hearing handicap status. Furthermore, we aim to measure the effect of hearing handicap among the patients with dementia, as compared to a group of controls.
2.2. Demographic and neuropsychological assessment Data on age, gender and education (≥6 years and < 6 years of formal education) were obtained from review of medical records and through clinical interview including. Neuropsychological assessment included MMSE, MOCA and CDR interview, following a standard procedure. 2.3. Hearing assessment The hearing status of the study subjects consists of standardized comprehensive taste battery: 1) audiological relevant history and questionnaire, 2) visual otoscopy and tympanometry examination, 3) pure tone audiometry and 4) AIADH questionnaire. 2.3.1. Audiological relevant history and questionnaire Prior to clinical examination, audiological relevant history (e.g. presence of vertigo and tinnitus, occupation, history of exposure of chemicals, ototoxic drugs, noise exposure and radiation, family history, history of head and neck trauma and injury) was obtained through verbal interview to elicit evidence of hearing impairment. These were also confirmed with the subject's closet caregiver. 2.3.2. Otoscopy and tympanometry Otoscopy and tympanometry was done to exclude external and middle ear pathology. 2.3.3. Pure tone audiometry In order to determine severity of hearing loss a pure tone audiometry was conducted in all participants using the Hughson and Westlake method for each octave frequency within the range of 250 Hz to 4000 Hz. Pure tone average (PTA) of hearing threshold at 500 HZ, 1000 HZ, 2000HZ and 4000HZ was calculated and reported in dB. Higher PTA values indicating poor hearing ability. In this study PTA of the better ear > 40 dB was considered as disabling hearing loss based on WHO criteria elderly [6]. 2.3.4. Amsterdam inventory of auditory disability and handicap In order to determine the severity of hearing handicap, all participants were interviewed verbally using the Amsterdam Inventory of Auditory Disability and Handicap (AIADH) and hearing handicap score was recorded. This interview was conducted together with caregiver to rule out any possibility of inaccurate information about their hearing. The AIADH is a 30-item questionnaire, which looks into five basic disability domains (distinction of sound, auditory localization,
2. Materials and methods 2.1. Study population For the present study, a case-control design was used. Cases were defined as patients with subjective memory complains and impairment on comprehensive neuropsychological assessment and were diagnosed 2
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
intelligibility in noise, and intelligibility in quite, detections of sounds) for everyday listening situations [8]. Subjects rated their daily listening difficulties with the following severity levels: almost never = 3, occasionally = 2, frequently = 1, almost always = 0. Total AIADH score was calculated for each subject, the higher the score, the less hearing handicap effect on the subject.
Table 1 Baseline characteristics of participants. Characteristics
2.4. Diagnosis of dementia The diagnosis of dementia was confirmed in weekly consensus meetings consisting of neurologists, psychologists, and research staffs of patients seen at the Memory Clinic. Diagnostic evaluations involved the patient's past and present medical history, physical examination, blood tests and neuropsychological assessment. Diagnosis of dementia was based the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). The severity of dementia was assessed by the Global Clinical Dementia Rating (CDR) Score (0-none, 0.5-very mild, 1mild, 2-moderate, 3-severe) [30]. Only patients with CDR score of 1 were recruited into this study.
Dementia (n = 39)
Control (n = 52)
p-Value
Demographic factors Age, median (IQR) Gender (female), n (%) Education (≥ 6 years), n (%)
78.4 (10) 23 (59.0) 17 (43.6)
72.8 (8) 23 (44.2) 43 (82.7)
< 0.001 0.164 < 0.001
Cognitive assessment MMSE, median (IQR) MoCA, median (IQR)
17 (14) 12 (6)
27.5 (3) 26 (5)
< 0.001 < 0.001
8 (21.1)
17 (32.7)
0.223
17 (44.7)
13 (25.0)
0.050
1 (2.6)
4 (7.7)
0.392
8 (21.1)
3 (5.8)
0.029
75 (11) 19 (48.7)
80 (10) 13 (25.0)
< 0.001 0.019
40.0 (20)
30.5 (18)
0.011
Audiology relevant history History of noise exposure, (yes), n (%) History of use of ototoxic drug, (yes), n (%) Family history of HL, (yes), n (%) History of trauma and injury, (yes), n (%) Hearing assessment AIADH score, median (IQR) Disabling hearing loss (> 40 dB) (Yes), n (%) PTA average (better ear), median, (IQR)
2.5. Statistical analysis In order to examine the differences between patients with and without dementia, the Mann-Whitney U test was performed for skewed distributed continuous variables (age, PTA, AIADH score) and chisquare test for dichotomous variables (gender and audiology relevant history). For the purpose of this study, PTA in decibels were further grouped into 2 categorical variables (< 40 dB HL and > 40 dB HL) to find out the actual numbers of participants with disabling hearing loss in memory clinic. Linear regression models were constructed with mean differences (β) and 95% confidence intervals (CI) to determine the association between hearing loss measured by PTA and dementia. In the regression model PTA was treated as dependent factor and dementia diagnosis was treated as independent variable. The same regression models were further used to determine the association between hearing handicap measured by AIADH and dementia where AIADH was treated as dependent and dementia as independent variables. As there are potential confounders in this study such as age, gender, education, audiological relevant history multivariate models were constructed to eliminate the effects of these confounders [31]. Multiple linear regression can eliminate the confounding effect and isolate the relationship of interest [31]. All the models were first adjusted for age and gender education (model I). Previous studies have shown the effect of noise exposure, ototoxic drug, family history and trauma on hearing [32,33], additional adjustments were made for audiological relevant history (noise exposure, use of ototoxic drug, family history of hearing loss, history of trauma and injury) (model II). Finally adjusted for AIADH and PTA respectively (model III). To demonstrate the independent effects of hearing loss on dementia and hearing handicap on dementia, on possible outcomes from age, quadratic term (age and age2) was entered in all regression models [34]. The tests were considered significant at p < 0.05. All the data were analyzed using SPSS software package (version 25).
Abbreviations: MMSE, Mini–Mental State Examination; MoCA, Montreal Cognitive Assessment; HL, Hearing loss; AIADH, Amsterdam Inventory for Auditory Disability and Handicap; PTA, pure tone audiometry average. p-Value < 0.05 was considered statistically significant. Bold values represent statistically significant associations.
4000 Hz in left ear and right ear in control and dementia groups. Compared to controls patients with dementia have higher average hearing thresholds at most of the frequencies. Table 2 summarizes the adjusted models using linear regression for association of hearing loss and hearing handicap with dementia. With regards to hearing loss, higher PTA was not associated with dementia after adjusting for age, gender and education in model I (β = 3.18; 95% CI = −2.29, 8.66, p = 0.251) and in model II further adjusting for audiology-relevant history (β = 2.12; 95% CI = −3.77, 8.01, p = 0.476) also did not change the association. However, in age, gender and education adjusted model significantly more patients with dementia had lower AIADH score compared to non-demented controls (β = −8.34; 95% CI = −13.82, −2.85, p = 0.003). This association still remained significant after further adjusting audiology-relevant history in model II (β = −6.94; 95% CI = −12.67, −1.20, p = 0.018) and PTA in model III (β: −6.40; 95% CI: −11.99, −0.81, p = 0.025) (Fig. 2). 4. Discussion The present study demonstrated 48.7% of the patients with dementia from memory clinic and 25.0% of non-demented controls had disabling hearing loss. Significantly more patients with dementia were hearing handicapped (lower AIADH score) as compared to non-demented controls. There was no significant association between the higher PTA and dementia. In our study, 48.7% of patients with dementia had disabling hearing loss, which is higher than the controls and the general elderly population (age > 70 years) in Singapore [19]. Moreover, our result in patients with dementia is comparable to the American and Brazilian cognitively impaired populations: 60% and 68.9% respectively [13,14]. These results show that patients with dementia and subjects with cognitively impairment have more hearing impairment compared to the general population globally. In the present study, However PTA of subjects with dementia is
3. Results Table 1 shows the baseline characteristics of the study subjects. Patients with dementia were significantly older, with lower AIADH scores (p < 0.001) than controls. Patients with dementia had significantly higher MMSE (median score; 27.5 vs 17) and MoCA (median score 26 vs 12) scores compared to controls (p < 0.001). 48.7% of subjects with dementia and 25.0% of non-demented subjects had disabling hearing loss (p = 0.019). With regard to hearing loss subjects with dementia had higher PTA compared to non-demented controls (p = 0.011). Fig. 1 shows the average hearing thresholds at 500 Hz to 3
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
Fig. 1. The average hearing thresholds at 500 Hz to 4000 Hz in left ear (A) and right ear (B) in control and dementia groups. Table 2 Association between hearing loss (PTA average) and hearing handicap (AIADH) with dementia.
Model I Model II Model III
PTA average (better ear) β (95% CI)
AIADH score β (95% CI)
3.18 (−2.29, 8.66) p = .251 2.12 (−3.77, 8.01) p = .476 0.27 (−5.66, 6.20) * p = .928
−8.34 (−13.82–2.85) p = .003 −6.94 (−12.67,−1.20) p = .018 −6.40(−11.99,−0.81) # p = .025
Abbreviations: PTA, pure tone audiometry; AIADH, Amsterdam Inventory for Auditory Disability and Handicap; β, mean difference; CI, confidence interval. Model I: included age, age2, gender and education. Model II: included age, age2, gender, education, history of use of ototoxic drug, history of trauma / injury, history of noise exposure and family history of hearing loss. Model III: *, Model II+ AIADH; #, Model II + PTA average. p-value < 0.05 was considered statistically significant. Bold values represent statistically significant associations.
Fig. 2. Association between AIADH and dementia.
that their memory, attention and judgement should not be severely impaired yet and this interview was conducted together with their personal caregivers. Furthermore, these demented subjects had not demonstrated difficulty following instructions during audiometric assessment. We speculate that, the association between hearing handicap and dementia may instead be due to other age related cognitive disorders and changes in central auditory processing areas, or combination of both [35]. Studies conducted by Gates et al. [7,25,36], and Tuwaig et al. [26,37]. on Alzheimer's dementia patients demonstrated that damage or dysfunction of the central auditory pathways to be
significantly higher than non-demented controls (41.5 dB vs 30.5 dB) but after adjusting for possible confounders such as age, gender, education, audiology-relevant history there was no significant difference in PTA of subjects with dementia and controls. Moreover, patients with dementia were more hearing handicapped compared to the controls, independent of age, gender, audiology-relevant history and peripheral hearing status. This cannot be attributed to the inaccuracy of information provided by the demented subjects during the administration of their AIADH, as their global CDR score was only 1, which indicates 4
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
education, communication strategies, instruction on use and maintenance of an amplification device was found to improve their communication, reduce symptom burden and improve quality of life [53]. The present study has some limitations. First, PTA and neuropsychological examination was done at only one-time point so we are unable to evaluate the longitudinal changes in hearing status and dementia severity. Second, patients with dementia may provide inaccurate information about their hearing history and unable to follow instructions. However, in this study we recruited patients with mild dementia with global CDR score 1, which may imply that memory, attention and judgement of our patients is not severely impaired. Furthermore, our patients did not demonstrate difficulty following instructions during audiometric assessment. Third, detailed central auditory processing test and brain magnetic resonance imaging scan were not part of the outcome measures therefore unable to study the neurodegenerative and vascular changes in both groups of subjects. Fourth, after adjusting for demographics and several risk factors, we cannot ignore the possibility of residual confounding. Fifth, our study sample may likely suffer from selection bias because caregivers and spouses who are recruited as controls are relatively healthier than their similar aged peers. Sixth, most of the tests such as MMSE, MoCA, CDR and AIADH are conducted via oral interview. It may be possible that our patients with dementia had poor hearing hence they would have poor access to teat materials and preform worse. Thus, we cannot ignore the possibility of measurement bias. However, in this study we found that both controls and subjects with dementia had some degree of hearing loss (median PTA average 40 dBHL vs 30.5 dBHL). Lastly, our sample size for this study was relatively small and as this study was conducted in an Asian population; our results may not be generalizable to other ethnicities. Furthermore, the confidence interval for the association between AIADH and dementia is wide this may be just a reflection of small sample size; hence this result should be interpreted with caution. Nonetheless, the present study has consistently showed that patients with dementia are more prevalent for hearing impairment and hearing handicap, similar to those reported in the literature. Thus further studies with larger sample size investigating peripheral and central auditory test and brain MRI scan are required to examine the exact mechanistic link between hearing impairment and dementia.
associated with dementia depending on the severity of disease. Since dementia is a disease of the central nervous system, there might be involvement of central auditory dysfunction in the patients with dementia that contributed to the higher hearing handicapping effect reported in this study, rather than just merely a peripheral hearing deficit. Even though our study did not explicitly investigate the central auditory processing functions in our patients, central auditory processing disorder is commonly reported in dementia, even at its preclinical stage [25,37], so it serves some basis to our speculation. Higher order auditory processing may be affected by dementia-related pathology such as neurodegeneration, deposition of amyloid beta and tau and microvascular changes. Histopathological study in Alzheimer's disease patients showed the evidence of specific pattern of neurodegeneration in the auditory system and deposition of amyloid beta and tau in auditory areas in the brain especially in the medial geniculate body and inferior colliculus [38]. These structures are important relay stations between the cochlea and auditory cortex. Several cross-sectional neuroimaging studies in older adults have demonstrated that hearing loss is related to alterations in gray and white mater especially in the primary auditory cortex [39,40] and variations in central auditory white matter tracks integrity [41,42]. A recent longitudinal neuroimaging study by Lin et al. with > 6.4 years of follow-up showed a faster rate of brain atrophy in older adults (age 56–86 years) with hearing impairment compared to those with normal hearing [43]. Atrophy in the right superior, middle, and inferior temporal gyri was observed in these hearing impaired patients [43]. These regions are found to be involved in preclinical and early stage Alzheimer's disease and are important for spoken language processing, semantic memory and sensory integration [44,45]. Studies have also shown that hearing loss and dementia share common risk factors such as aging, hyperlipedemia, hypertension, diabetes and cerebrovascular diseases [46,47]. Hypertensive microvascular disease may impair function of both the cochlea and central auditory system affecting cochlear homeostasis and ischemic brain changes such as white matter hyperintensities respectively [48]. Hearing impairment in patients with dementia may be due to the combined effect of aging, microvascular and neurodegenerative changes. On the other hand, hearing impairment could adversely affect cognition and thereby increasing the risk of dementia by adding to the previously existing dementia-related brain pathology such as amyloid beta, tau and cerebrovascular disease [49]. Previous studies have shown that peripheral auditory dysfunction is an early manifestation of ARHL and is associated with cognitive impairment and dementia [21–24]. However, in this study we were unable to support those findings. Furthermore, we have not found any histopathological studies reporting the involvement of dementia pathology in peripheral auditory system disease. PTA only determines the quantitative aspect of hearing loss and may not completely reflect the impact of hearing loss on daily activities [50]. In this present study, the dementia patients were completely unware about their hearing problems, and did not seek any medical consultation before. In this study we showed that hearing handicap as measured by AIADH is associated with dementia in memory clinic patients. However, the hearing ability of patients is often ignored during dementia investigation, and most of the older adults do not report hearing loss due to their compromised cognition, instead it is often perceived as an inconsequential process of aging and thus remains undiagnosed. Conducting a diagnostic hearing assessment in the memory clinic is not feasible due to resource constraints. A simple screening questionnaire such as AIADH would give the physician means to evaluate the effect of hearing impairment on these patients' daily life and plan for further management. Studies have reported that the use of hearing aids has been shown to promote social engagement and improve communication, cognition and emotional function of elderly with hearing loss [51,52]. Furthermore, a recent study in persons with dementia has shown that the use of non-interventional approach such as hearing loss
5. Conclusion Our study showed that hearing handicap is more frequent among patients with dementia than healthy controls despite no significant difference in terms of their peripheral hearing acuity level. The mechanism of this association between hearing handicap and dementia requires further research and may involve higher order auditory dysfunction. We emphasize the need for routine hearing assessment in older people who are at risk of hearing impairment and dementia. This is in view that screening for at risk population in its earliest stages might be useful for therapeutic targets aimed at delaying the progression of disease. Declaration of competing interest All authors declare no conflict of interest regarding this manuscript. Acknowledgement We acknowledge all the Memory Aging & Cognition Centre, National University Hospital coordinators for their contribution to recruitment and data acquisition. Author's contribution BG participated in data acquisition, performed analysis, drafted and revised manuscript. SH, NV and CC were responsible for provided 5
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
intellectual advice and revised manuscript. JHYL was responsible for study design and concept, data collection, overall supervision and revised the manuscript.
Gerontol 1986;4(3):3–15. [25] Gates GA, Anderson ML, Feeney MP, McCurry SM, Larson EB. Central auditory dysfunction in older people with memory impairment or Alzheimer’s dementia. Arch Otolaryngol Head Neck Surg 2008;134(7):771–7. [26] Tuwaig M, Savard M, Jutras B, Lamarre-Théroux L, Poirier J, Breitner JCS. Central auditory processing in individuals at risk for Alzheimer's dementia. Alzheimers Dement.11(7):509. [27] Meijer AG, Wit HP, TenVergert EM, Albers FW, Muller Kobold JE. Reliability and validity of the (modified) Amsterdam Inventory for Auditory Disability and Handicap. Int J Audiol 2003;42(4):220–6. [28] Zanchetta S, Simoes HO, Lunardelo PP, Canavezi MO, Reis A, Massuda ET. Crosscultural adaptation of the Amsterdam inventory for auditory disability and handicap to Brazilian Portuguese. (pii: S1808-8694(18)30123-X). Braz J Otorhinolaryngol2018. https://doi.org/10.1016/j.bjorl.2018.07.011. [Epub ahead of print]. [29] Boeschen Hospers JM, Smits N, Smits C, Stam M, Terwee CB, Kramer SE. Reevaluation of the Amsterdam inventory for auditory disability and handicap using item response theory. J Speech Lang Hear Res 2016;59(2):373–83. [30] Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140(6):566–72. [31] Pourhoseingholi MA, Baghestani AR, Vahedi M. How to control confounding effects by statistical analysis. Gastroenterol Hepatol Bed Bench 2012;5(2):79–83. [32] Lee JS, Choi HG, Jang JH, Sim S, Hong SK, Lee H-J, et al. Analysis of predisposing factors for hearing loss in adults. J Korean Med Sci 2015;30(8):1175–82. [33] Lie A, Skogstad M, Johannessen HA, Tynes T, Mehlum IS, Nordby K-C, et al. Occupational noise exposure and hearing: a systematic review. Int Arch Occup Environ Health 2016;89(3):351–72. [34] Hilal S, Ikram MA, Verbeek MM, Franco OH, Stoops E, Vanderstichele H, et al. Creactive protein, plasma amyloid-beta levels, and their interaction with magnetic resonance imaging markers. Stroke 2018;49(11):2692–8. [35] Martin JS, Jerger JF. Some effects of aging on central auditory processing. J Rehabil Res Dev 2005;42(4 Suppl 2):25–44. [36] Gates GA, Beiser A, Rees TS, D’Agostino RB, Wolf PA. Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer’s disease. J Am Geriatr Soc 2002;50(3):482–8. [37] Tuwaig M, Savard M, Jutras B, Poirier J, Collins DL, Rosa-Neto P, et al. Deficit in central auditory processing as a biomarker of pre-clinical Alzheimer’s disease. J Alzheimers Dis 2017;60(4):1589–600. [38] Sinha UK, Hollen KM, Rodriguez R, Miller CA. Auditory system degeneration in Alzheimer’s disease. Neurology 1993;43(4):779–85. [39] Eckert MA, Cute SL, Vaden Jr KI, Kuchinsky SE, Dubno JR. Auditory cortex signs of age-related hearing loss. J Assoc Res Otolaryngol 2012;13(5):703–13. [40] Husain FT, Medina RE, Davis CW, Szymko-Bennett Y, Simonyan K, Pajor NM, et al. Neuroanatomical changes due to hearing loss and chronic tinnitus: a combined VBM and DTI study. Brain Res 2011;1369:74–88. [41] Chang Y, Lee SH, Lee YJ, Hwang MJ, Bae SJ, Kim MN, et al. Auditory neural pathway evaluation on sensorineural hearing loss using diffusion tensor imaging. Neuroreport 2004;15(11):1699–703. [42] Lin Y, Wang J, Wu C, Wai Y, Yu J, Ng S. Diffusion tensor imaging of the auditory pathway in sensorineural hearing loss: changes in radial diffusivity and diffusion anisotropy. J Magn Reson Imaging 2008;28(3):598–603. [43] Lin FR, Ferrucci L, An Y, Goh JO, Doshi J, Metter EJ, et al. Association of hearing impairment with brain volume changes in older adults. Neuroimage 2014;90:84–92. [44] Peelle JE. The hemispheric lateralization of speech processing depends on what “speech” is: a hierarchical perspective. Front Hum Neurosci 2012;6:309. [45] Chetelat G, Landeau B, Eustache F, Mezenge F, Viader F, de la Sayette V, et al. Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage 2005;27(4):934–46. [46] Xipeng L, Ruiyu L, Meng L, Yanzhuo Z, Kaosan G, Liping W. Effects of diabetes on hearing and cochlear structures. J Otol 2013;8(2):82–7. [47] Evans MB, Tonini R, Shope CD, Oghalai JS, Jerger JF, Insull W, et al. Dyslipidemia and auditory function. Otol Neurotol 2006;27(5):609–14. [48] Eckert MA, Kuchinsky SE, Vaden KI, Cute SL, Spampinato MV, Dubno JR. White matter hyperintensities predict low frequency hearing in older adults. J Assoc Res Otolaryngol 2013;14(3):425–33. [49] Bernabei R, Bonuccelli U, Maggi S, Marengoni A, Martini A, Memo M, et al. Hearing loss and cognitive decline in older adults: questions and answers. Aging Clin Exp Res 2014;26(6):567–73. [50] Bagai A, Thavendiranathan P, Detsky AS. Does this patient have hearing impairment? JAMA 2006;295(4):416–28. [51] Maharani A, Dawes P, Nazroo J, Tampubolon G, Pendleton N. Longitudinal relationship between hearing aid use and cognitive function in older Americans. J Am Geriatr Soc 2018;66(6):1130–6. [52] Tsakiropoulou E, Konstantinidis I, Vital I, Konstantinidou S, Kotsani A. Hearing aids: quality of life and socio-economic aspects. Hippokratia 2007;11(4):183–6. [53] Mamo SK, Nirmalasari O, Nieman CL, McNabney MK, Simpson A, Oh ES, et al. Hearing care intervention for persons with dementia: a pilot study. Am J Geriatr Psychiatry 2017;25(1):91–101.
Funding This study was supported by the National Medical Research Council grants; NMRC/CG/NUHS/2010 - R-184-005-184-511, NMRC/CG/013/ 2013, NMRC/CIRG/1446/2016. References [1] Heger I, Deckers K, van Boxtel M, de Vugt M, Hajema K, Verhey F, et al. Dementia awareness and risk perception in middle-aged and older individuals: baseline results of the MijnBreincoach survey on the association between lifestyle and brain health. BMC Public Health 2019;19(1):678. [2] World Health Organization. Dementia Dec [cited 2019 Sept 7]. Available from. http://www.who.int/mediacentre/factsheets/fs362/en/; 2017. [3] Albers MW, Gilmore GC, Kaye J, Murphy C, Wingfield A, Bennett DA, et al. At the interface of sensory and motor dysfunctions and Alzheimer’s disease. Alzheimers Dement 2015;11(1):70–98. [4] Y-m Z, Lu D, L-p L, Zhang H, Y-y Z. Olfactory dysfunction in Alzheimer’s disease. Neuropsychiatr Dis Treat 2016;12:869–75. [5] Huang Q, Tang J. Age-related hearing loss or presbycusis. Eur Arch Otorhinolaryngol 2010;267(8):1179–91. [6] World Health Organization. Prevention of blindness and deafness Geneva [cited 2019 Sept 7]. Avaliable from. http://www.who.int/pbd/deafness/estimates/en/; 2018 Feb. [7] Gates GA, Cobb JL, Linn RT, Rees T, Wolf PA, D’Agostino RB. Central auditory dysfunction, cognitive dysfunction, and dementia in older people. Arch Otolaryngol Head Neck Surg 1996;122(2):161–7. [8] Kramer SE, Kapteyn TS, Festen JM, Tobi H. Factors in subjective hearing disability. Audiology 1995;34(6):311–20. [9] Panza F, Solfrizzi V, Logroscino G. Age-related hearing impairment-a risk factor and frailty marker for dementia and AD. Nat Rev Neurol 2015;11(3):166–75. [10] Adrait A, Perrot X, Nguyen MF, Gueugnon M, Petitot C, Collet L, et al. Do hearing aids influence behavioral and psychological symptoms of dementia and quality of life in hearing impaired Alzheimer’s disease patients and their caregivers? J Alzheimers Dis 2017;58(1):109–21. [11] Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet 2017;390(10113):2673–734. [12] Gold M, Lightfoot L, Hnath-Chisolm T. Hearing loss in a memory disorders clinic: a specially vulnerable population. Arch Neurol 1996;53(9):922–8. [13] Lopes L, Magaldi RM, Gândara MER, Reis AC, Jacob-Filho W. Prevalence of hearing impairment in patients with mild cognitive impairment. Dement Neuropsychol 2007;1(3):253–9. [14] Nirmalasari O, Mamo SK, Nieman CL, Simpson A, Zimmerman J, Nowrangi MA, et al. Age-related hearing loss in older adults with cognitive impairment. Int Psychogeriatr 2017;29(1):115–21. [15] Lin FR, Maas P, Chien W, Carey JP, Ferrucci L, Thorpe R. Association of skin color, race/ethnicity, and hearing loss among adults in the USA. J Assoc Res Otolaryngol 2012;13(1):109–17. [16] Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA. Inequalities in dementia incidence between six racial and ethnic groups over 14 years. Alzheimers Dement 2016;12(3):216–24. [17] Pratt SR, Kuller L, Talbott EO, McHugh-Pemu K, Buhari AM, Xu X. Prevalence of hearing loss in black and white elders: results of the cardiovascular health study. J Speech Lang Hear Res 2009;52(4):973–89. [18] National Population and Talent Division, Strategy Group. Prime Minister's Office Population.sg. Older Singaporeans to double by 2030 Aug 20 [cited 2019 Oct 12] Available from. https://www.population.sg/articles/older-singaporeans-to-doubleby-2030; 2017. [19] Lee JC, Danker AN, Wong YH, Lim MY. Hearing loss amongst the elderly in a Southeast Asian population - a community-based study. Ann Acad Med Singapore 2017;46(4):145–54. [20] Alzhimer'’s Disease International. Dementia in Asia Pacific Region International. Nov [cited 2018 Jul 7] 2014 Available from https://www.alz.co.uk/adi/pdf/ Dementia-Asia-Pacific-2014.pdf. [21] Lin FR, Metter E, O’Brien RJ, Resnick SM, Zonderman AB, Ferrucci L. Hearing loss and incident dementia. Arch Neurol 2011;68(2):214–20. [22] Peters CA, Potter JF, Scholer SG. Hearing impairment as a predictor of cognitive decline in dementia. J Am Geriatr Soc 1988;36(11):981–6. [23] Uhlmann RF, Larson EB, Rees TS, Koepsell TD, Duckert LG. Relationship of hearing impairment to dementia and cognitive dysfunction in older adults. JAMA 1989;261(13):1916–9. [24] Weinstein BE. Hearing loss and senile dementia in the institutionalized elderly. Clin
6
Contents lists available at ScienceDirect
Am J Otolaryngol journal homepage: www.elsevier.com/locate/amjoto
Hearing handicap in Asian patients with dementia Bibek Gyanwalia,b, Saima Hilala,b,c,g, Narayanaswamy Venketasubramaniand, ⁎ Christopher Chena,b, Jenny Hooi Yin Looe,f, a
Memory Aging & Cognition Centre, National University Health System, Singapore Department of Pharmacology, National University of Singapore, Singapore Departments of Epidemiology and Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands d Raffles Neuroscience Centre, Raffles Hospital, Singapore e Department of Otolaryngology, Head and Neck Surgery, National University Hospital, Singapore f Department of Otolaryngology, Head and Neck Surgery, National University Singapore, Singapore g Saw Swee Hock School of Public Health, National University of Singapore, Singapore b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Dementia Hearing handicap Hearing loss Memory clinic
Background: Hearing loss and hearing handicap may contribute to cognitive impairment and dementia. The purpose of this study was to analyze the association between hearing loss and hearing handicap with dementia in an Asian memory clinic parents. Methods: This study includes the data obtained from patients with mild dementia who attended the National University hospital memory clinic and non-demented healthy subjects among spouses and caregivers who are non-genetically related to our patients. All participants underwent comprehensive physical, medical, neuropsychological and audiological assessments (i.e. pure tone audiometry - PTA). Disabling hearing loss was defined as a hearing loss of > 40 dB in the better ear on PTA. Amsterdam Inventory for Auditory Disability and Handicap (AIADH) questionnaire was administered through the verbal interview to measure their hearing handicap score. Linear regression models were used to investigate the association between hearing loss and hearing handicap with dementia. Mean differences (β) with 95% confidence intervals (CI) were calculated. Results: 91 participants (65–90 years old) were recruited for this study; 39 of them were patients with dementia and 52 were non-demented healthy controls. 48.7% of the patients with dementia had disabling hearing loss, which is higher than the non-demented controls (25.0%) (p = 0.019). The significant association between hearing handicap (as measured by AIADH) and dementia was observed, which was independent of demographic factors and audiology related history and PTA average (β = −6.40; 95% CI =0.11.99, −0.81, p = 0.025). There was no independent association between hearing loss and dementia (p > 0.05). Conclusion: A significant association between hearing handicap and dementia was found. The mechanism of this association requires further research and may involve higher order central processing disorder.
1. Introduction Dementia has become one of the most important public health concerns [1]. In 2017 the World Health Organization (WHO) estimated that 50 million people worldwide are living with dementia, which is expected to triple by 2050 [2]. Dementia is a chronic progressive syndrome characterized by loss of cognitive functions [2]. In addition to loss of cognitive functions, dementia can also affect perception senses [3,4]. Among them auditory sense is most commonly affected, which manifests as hearing loss [3,4]. Interestingly, hearing loss is one of the most common sensory deficits in the elderly [5]. In 2018, WHO reported that 6.1% of global population had hearing loss, and one- third ⁎
of them were the elderly [6]. Approximately 50% of those cases with hearing loss occur in low economic countries in Asia and Africa, which show an uneven distribution of disease burden across the region [6]. Hearing loss typically begins by affecting the perception of high frequencies sound, which compromise speech understanding comprehension and communication [7]. Furthermore, elderly subjects with hearing loss experiences difficulty in distinction, localization and detection of sound, which may affect their everyday listening [8]. In this way, hearing loss thus, has significant psychological, physical, social and cognitive consequences [9]. Hearing loss is considered as one of the modified risk factor of dementia [9]. Hearing loss can be modified by the use of hearing aid and
Corresponding author at: National University Hospital Medical Centre, Level 15, ENT, Head & Neck Surgery Clinic, Singapore 119074, Singapore. E-mail address: [email protected] (J.H.Y. Loo).
https://doi.org/10.1016/j.amjoto.2019.102377 Received 31 October 2019 0196-0709/ © 2019 Published by Elsevier Inc.
Please cite this article as: Bibek Gyanwali, et al., Am J Otolaryngol, https://doi.org/10.1016/j.amjoto.2019.102377
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
as mild dementia [Global Clinical Dementia Rating (CDR) Score = 1)]. Controls were defined as patients who were cognitively normal on objective neuropsychological assessments and with no functional loss and were classified as non-demented subjects. 39 subjects with mild dementia as clinical convenience sample were recruited from the memory clinic at the National University Hospital, while 52 healthy non-demented subjects were recruited among spouse or caregivers of patients who were not genetically related to our patients. All the subjects underwent comprehensive physical, medical, neuropsychological [which included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA) and CDR interview] and audiological assessments. Assessments were made in a single session which lasted for approximately 1 h. Breaks were introduced if subjects felt tired. None of our subjects were previous and current users of hearing aid or had any hearing implants. Hearing amplification device was not used during the clinical and audiological assessments. Written consent was obtained for each participant prior to the procedures. This study was approved by the National Health Group (Domain D) ethics board with reference number DSRB Ref: 2011/ 01610.
other hearing assistive devices [10]. A recent study by Livingston et al. suggested that mid-life hearing loss is responsible for 9% of dementia cases [11]. In 1996 Gold et al. reported that > 90% of elderly patients with dementia had hearing loss [12]. Moreover, the prevalence reported in this study is probably higher than general age matched population. Another study conducted in Brazilian and American elderly patients with cognitive impairment reported the prevalence of hearing impairment as 68.9% and 60% respectively [13,14]. Prevalence of dementia and hearing loss differs in different studies, which is not surprising given the different genetic composition, risk factors, and environmental exposure in different ethnicities [15–17]. While these studies indicate different prevalence rate across population hence these studies need to be validated with more recent data and across different population such as in Asia. In Asian countries such as Japan, Korea, China and Singapore with the increasing number of elderly population, a higher number of parents with dementia and hearing loss are expected, which will increase the socio-economic and healthcare burden of the country [18]. Singapore is one of the countries in Asia with the most rapidly aging population [18] A study conducted by Lee et al. in a community-based population reported that > 22% of elderly above 65 years old had hearing loss [19]. This problem will grow even more serious given that the number of elderly Singaporeans above 65 years is expected to double from 1 in 8 in 2015 to 1 in 4 in 2030 [18]. Similarly, recent statistics from the Alzheimer's Disease Association predicts an exponential increase in patients with dementia in Singapore from 53,000 dementia patients by 2020, to more than triple to 187,000 by 2050 [20]. This situation is also similar in other Asian countries, thus there is need to investigate the association between hearing loss and dementia and its preventive measures. In investigating the association between hearing loss and dementia previous studies reported significant association between poor hearing dementia [21–24] whereas others did not [7,25,26]. None of these studies reported on the additional handicaping effect of hearing loss in elderly with dementia in their everyday life. In patients with dementia, cognitive impairment and hearing impairment have synergistic effect manifesting as hearing handicap [27,28]. It has been shown that selfreported hearing disability measured by Amsterdam Inventory for Auditory Disability and Handicap (AIADH) is of the appropriate test batteries to measure hearing handicap [27–29]. A simple screening questionnaire such as AIADH would help the memory clinic physician to evaluate the hearing handicapping effect in patients with dementia. To date, no guidelines are provided to mandate hearing screening as part of the routine neurocognitive assessment for patients with cognitive impairment. Therefore, it remains uncertain how many patients diagnosed with dementia in memory clinics also present with hearing loss or hearing handicap, Moreover, the influence of hearing impairment on diagnosis of dementia is still unknown. Hence, it is still unclear if hearing loss or hearing handicap can be considered as a risk factor for dementia. In view of these gaps, we hypothesized that: [1] more number of patients with dementia has hearing loss and hearing handicap compared to non-demented subjects in memory clinic and [2] hearing loss and hearing handicap are associated with dementia. In this study we aim to study the establish the baseline hearing profile of patients with dementia seen at National University Hospital, Memory Clinic and their hearing handicap status. Furthermore, we aim to measure the effect of hearing handicap among the patients with dementia, as compared to a group of controls.
2.2. Demographic and neuropsychological assessment Data on age, gender and education (≥6 years and < 6 years of formal education) were obtained from review of medical records and through clinical interview including. Neuropsychological assessment included MMSE, MOCA and CDR interview, following a standard procedure. 2.3. Hearing assessment The hearing status of the study subjects consists of standardized comprehensive taste battery: 1) audiological relevant history and questionnaire, 2) visual otoscopy and tympanometry examination, 3) pure tone audiometry and 4) AIADH questionnaire. 2.3.1. Audiological relevant history and questionnaire Prior to clinical examination, audiological relevant history (e.g. presence of vertigo and tinnitus, occupation, history of exposure of chemicals, ototoxic drugs, noise exposure and radiation, family history, history of head and neck trauma and injury) was obtained through verbal interview to elicit evidence of hearing impairment. These were also confirmed with the subject's closet caregiver. 2.3.2. Otoscopy and tympanometry Otoscopy and tympanometry was done to exclude external and middle ear pathology. 2.3.3. Pure tone audiometry In order to determine severity of hearing loss a pure tone audiometry was conducted in all participants using the Hughson and Westlake method for each octave frequency within the range of 250 Hz to 4000 Hz. Pure tone average (PTA) of hearing threshold at 500 HZ, 1000 HZ, 2000HZ and 4000HZ was calculated and reported in dB. Higher PTA values indicating poor hearing ability. In this study PTA of the better ear > 40 dB was considered as disabling hearing loss based on WHO criteria elderly [6]. 2.3.4. Amsterdam inventory of auditory disability and handicap In order to determine the severity of hearing handicap, all participants were interviewed verbally using the Amsterdam Inventory of Auditory Disability and Handicap (AIADH) and hearing handicap score was recorded. This interview was conducted together with caregiver to rule out any possibility of inaccurate information about their hearing. The AIADH is a 30-item questionnaire, which looks into five basic disability domains (distinction of sound, auditory localization,
2. Materials and methods 2.1. Study population For the present study, a case-control design was used. Cases were defined as patients with subjective memory complains and impairment on comprehensive neuropsychological assessment and were diagnosed 2
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
intelligibility in noise, and intelligibility in quite, detections of sounds) for everyday listening situations [8]. Subjects rated their daily listening difficulties with the following severity levels: almost never = 3, occasionally = 2, frequently = 1, almost always = 0. Total AIADH score was calculated for each subject, the higher the score, the less hearing handicap effect on the subject.
Table 1 Baseline characteristics of participants. Characteristics
2.4. Diagnosis of dementia The diagnosis of dementia was confirmed in weekly consensus meetings consisting of neurologists, psychologists, and research staffs of patients seen at the Memory Clinic. Diagnostic evaluations involved the patient's past and present medical history, physical examination, blood tests and neuropsychological assessment. Diagnosis of dementia was based the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). The severity of dementia was assessed by the Global Clinical Dementia Rating (CDR) Score (0-none, 0.5-very mild, 1mild, 2-moderate, 3-severe) [30]. Only patients with CDR score of 1 were recruited into this study.
Dementia (n = 39)
Control (n = 52)
p-Value
Demographic factors Age, median (IQR) Gender (female), n (%) Education (≥ 6 years), n (%)
78.4 (10) 23 (59.0) 17 (43.6)
72.8 (8) 23 (44.2) 43 (82.7)
< 0.001 0.164 < 0.001
Cognitive assessment MMSE, median (IQR) MoCA, median (IQR)
17 (14) 12 (6)
27.5 (3) 26 (5)
< 0.001 < 0.001
8 (21.1)
17 (32.7)
0.223
17 (44.7)
13 (25.0)
0.050
1 (2.6)
4 (7.7)
0.392
8 (21.1)
3 (5.8)
0.029
75 (11) 19 (48.7)
80 (10) 13 (25.0)
< 0.001 0.019
40.0 (20)
30.5 (18)
0.011
Audiology relevant history History of noise exposure, (yes), n (%) History of use of ototoxic drug, (yes), n (%) Family history of HL, (yes), n (%) History of trauma and injury, (yes), n (%) Hearing assessment AIADH score, median (IQR) Disabling hearing loss (> 40 dB) (Yes), n (%) PTA average (better ear), median, (IQR)
2.5. Statistical analysis In order to examine the differences between patients with and without dementia, the Mann-Whitney U test was performed for skewed distributed continuous variables (age, PTA, AIADH score) and chisquare test for dichotomous variables (gender and audiology relevant history). For the purpose of this study, PTA in decibels were further grouped into 2 categorical variables (< 40 dB HL and > 40 dB HL) to find out the actual numbers of participants with disabling hearing loss in memory clinic. Linear regression models were constructed with mean differences (β) and 95% confidence intervals (CI) to determine the association between hearing loss measured by PTA and dementia. In the regression model PTA was treated as dependent factor and dementia diagnosis was treated as independent variable. The same regression models were further used to determine the association between hearing handicap measured by AIADH and dementia where AIADH was treated as dependent and dementia as independent variables. As there are potential confounders in this study such as age, gender, education, audiological relevant history multivariate models were constructed to eliminate the effects of these confounders [31]. Multiple linear regression can eliminate the confounding effect and isolate the relationship of interest [31]. All the models were first adjusted for age and gender education (model I). Previous studies have shown the effect of noise exposure, ototoxic drug, family history and trauma on hearing [32,33], additional adjustments were made for audiological relevant history (noise exposure, use of ototoxic drug, family history of hearing loss, history of trauma and injury) (model II). Finally adjusted for AIADH and PTA respectively (model III). To demonstrate the independent effects of hearing loss on dementia and hearing handicap on dementia, on possible outcomes from age, quadratic term (age and age2) was entered in all regression models [34]. The tests were considered significant at p < 0.05. All the data were analyzed using SPSS software package (version 25).
Abbreviations: MMSE, Mini–Mental State Examination; MoCA, Montreal Cognitive Assessment; HL, Hearing loss; AIADH, Amsterdam Inventory for Auditory Disability and Handicap; PTA, pure tone audiometry average. p-Value < 0.05 was considered statistically significant. Bold values represent statistically significant associations.
4000 Hz in left ear and right ear in control and dementia groups. Compared to controls patients with dementia have higher average hearing thresholds at most of the frequencies. Table 2 summarizes the adjusted models using linear regression for association of hearing loss and hearing handicap with dementia. With regards to hearing loss, higher PTA was not associated with dementia after adjusting for age, gender and education in model I (β = 3.18; 95% CI = −2.29, 8.66, p = 0.251) and in model II further adjusting for audiology-relevant history (β = 2.12; 95% CI = −3.77, 8.01, p = 0.476) also did not change the association. However, in age, gender and education adjusted model significantly more patients with dementia had lower AIADH score compared to non-demented controls (β = −8.34; 95% CI = −13.82, −2.85, p = 0.003). This association still remained significant after further adjusting audiology-relevant history in model II (β = −6.94; 95% CI = −12.67, −1.20, p = 0.018) and PTA in model III (β: −6.40; 95% CI: −11.99, −0.81, p = 0.025) (Fig. 2). 4. Discussion The present study demonstrated 48.7% of the patients with dementia from memory clinic and 25.0% of non-demented controls had disabling hearing loss. Significantly more patients with dementia were hearing handicapped (lower AIADH score) as compared to non-demented controls. There was no significant association between the higher PTA and dementia. In our study, 48.7% of patients with dementia had disabling hearing loss, which is higher than the controls and the general elderly population (age > 70 years) in Singapore [19]. Moreover, our result in patients with dementia is comparable to the American and Brazilian cognitively impaired populations: 60% and 68.9% respectively [13,14]. These results show that patients with dementia and subjects with cognitively impairment have more hearing impairment compared to the general population globally. In the present study, However PTA of subjects with dementia is
3. Results Table 1 shows the baseline characteristics of the study subjects. Patients with dementia were significantly older, with lower AIADH scores (p < 0.001) than controls. Patients with dementia had significantly higher MMSE (median score; 27.5 vs 17) and MoCA (median score 26 vs 12) scores compared to controls (p < 0.001). 48.7% of subjects with dementia and 25.0% of non-demented subjects had disabling hearing loss (p = 0.019). With regard to hearing loss subjects with dementia had higher PTA compared to non-demented controls (p = 0.011). Fig. 1 shows the average hearing thresholds at 500 Hz to 3
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
Fig. 1. The average hearing thresholds at 500 Hz to 4000 Hz in left ear (A) and right ear (B) in control and dementia groups. Table 2 Association between hearing loss (PTA average) and hearing handicap (AIADH) with dementia.
Model I Model II Model III
PTA average (better ear) β (95% CI)
AIADH score β (95% CI)
3.18 (−2.29, 8.66) p = .251 2.12 (−3.77, 8.01) p = .476 0.27 (−5.66, 6.20) * p = .928
−8.34 (−13.82–2.85) p = .003 −6.94 (−12.67,−1.20) p = .018 −6.40(−11.99,−0.81) # p = .025
Abbreviations: PTA, pure tone audiometry; AIADH, Amsterdam Inventory for Auditory Disability and Handicap; β, mean difference; CI, confidence interval. Model I: included age, age2, gender and education. Model II: included age, age2, gender, education, history of use of ototoxic drug, history of trauma / injury, history of noise exposure and family history of hearing loss. Model III: *, Model II+ AIADH; #, Model II + PTA average. p-value < 0.05 was considered statistically significant. Bold values represent statistically significant associations.
Fig. 2. Association between AIADH and dementia.
that their memory, attention and judgement should not be severely impaired yet and this interview was conducted together with their personal caregivers. Furthermore, these demented subjects had not demonstrated difficulty following instructions during audiometric assessment. We speculate that, the association between hearing handicap and dementia may instead be due to other age related cognitive disorders and changes in central auditory processing areas, or combination of both [35]. Studies conducted by Gates et al. [7,25,36], and Tuwaig et al. [26,37]. on Alzheimer's dementia patients demonstrated that damage or dysfunction of the central auditory pathways to be
significantly higher than non-demented controls (41.5 dB vs 30.5 dB) but after adjusting for possible confounders such as age, gender, education, audiology-relevant history there was no significant difference in PTA of subjects with dementia and controls. Moreover, patients with dementia were more hearing handicapped compared to the controls, independent of age, gender, audiology-relevant history and peripheral hearing status. This cannot be attributed to the inaccuracy of information provided by the demented subjects during the administration of their AIADH, as their global CDR score was only 1, which indicates 4
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
education, communication strategies, instruction on use and maintenance of an amplification device was found to improve their communication, reduce symptom burden and improve quality of life [53]. The present study has some limitations. First, PTA and neuropsychological examination was done at only one-time point so we are unable to evaluate the longitudinal changes in hearing status and dementia severity. Second, patients with dementia may provide inaccurate information about their hearing history and unable to follow instructions. However, in this study we recruited patients with mild dementia with global CDR score 1, which may imply that memory, attention and judgement of our patients is not severely impaired. Furthermore, our patients did not demonstrate difficulty following instructions during audiometric assessment. Third, detailed central auditory processing test and brain magnetic resonance imaging scan were not part of the outcome measures therefore unable to study the neurodegenerative and vascular changes in both groups of subjects. Fourth, after adjusting for demographics and several risk factors, we cannot ignore the possibility of residual confounding. Fifth, our study sample may likely suffer from selection bias because caregivers and spouses who are recruited as controls are relatively healthier than their similar aged peers. Sixth, most of the tests such as MMSE, MoCA, CDR and AIADH are conducted via oral interview. It may be possible that our patients with dementia had poor hearing hence they would have poor access to teat materials and preform worse. Thus, we cannot ignore the possibility of measurement bias. However, in this study we found that both controls and subjects with dementia had some degree of hearing loss (median PTA average 40 dBHL vs 30.5 dBHL). Lastly, our sample size for this study was relatively small and as this study was conducted in an Asian population; our results may not be generalizable to other ethnicities. Furthermore, the confidence interval for the association between AIADH and dementia is wide this may be just a reflection of small sample size; hence this result should be interpreted with caution. Nonetheless, the present study has consistently showed that patients with dementia are more prevalent for hearing impairment and hearing handicap, similar to those reported in the literature. Thus further studies with larger sample size investigating peripheral and central auditory test and brain MRI scan are required to examine the exact mechanistic link between hearing impairment and dementia.
associated with dementia depending on the severity of disease. Since dementia is a disease of the central nervous system, there might be involvement of central auditory dysfunction in the patients with dementia that contributed to the higher hearing handicapping effect reported in this study, rather than just merely a peripheral hearing deficit. Even though our study did not explicitly investigate the central auditory processing functions in our patients, central auditory processing disorder is commonly reported in dementia, even at its preclinical stage [25,37], so it serves some basis to our speculation. Higher order auditory processing may be affected by dementia-related pathology such as neurodegeneration, deposition of amyloid beta and tau and microvascular changes. Histopathological study in Alzheimer's disease patients showed the evidence of specific pattern of neurodegeneration in the auditory system and deposition of amyloid beta and tau in auditory areas in the brain especially in the medial geniculate body and inferior colliculus [38]. These structures are important relay stations between the cochlea and auditory cortex. Several cross-sectional neuroimaging studies in older adults have demonstrated that hearing loss is related to alterations in gray and white mater especially in the primary auditory cortex [39,40] and variations in central auditory white matter tracks integrity [41,42]. A recent longitudinal neuroimaging study by Lin et al. with > 6.4 years of follow-up showed a faster rate of brain atrophy in older adults (age 56–86 years) with hearing impairment compared to those with normal hearing [43]. Atrophy in the right superior, middle, and inferior temporal gyri was observed in these hearing impaired patients [43]. These regions are found to be involved in preclinical and early stage Alzheimer's disease and are important for spoken language processing, semantic memory and sensory integration [44,45]. Studies have also shown that hearing loss and dementia share common risk factors such as aging, hyperlipedemia, hypertension, diabetes and cerebrovascular diseases [46,47]. Hypertensive microvascular disease may impair function of both the cochlea and central auditory system affecting cochlear homeostasis and ischemic brain changes such as white matter hyperintensities respectively [48]. Hearing impairment in patients with dementia may be due to the combined effect of aging, microvascular and neurodegenerative changes. On the other hand, hearing impairment could adversely affect cognition and thereby increasing the risk of dementia by adding to the previously existing dementia-related brain pathology such as amyloid beta, tau and cerebrovascular disease [49]. Previous studies have shown that peripheral auditory dysfunction is an early manifestation of ARHL and is associated with cognitive impairment and dementia [21–24]. However, in this study we were unable to support those findings. Furthermore, we have not found any histopathological studies reporting the involvement of dementia pathology in peripheral auditory system disease. PTA only determines the quantitative aspect of hearing loss and may not completely reflect the impact of hearing loss on daily activities [50]. In this present study, the dementia patients were completely unware about their hearing problems, and did not seek any medical consultation before. In this study we showed that hearing handicap as measured by AIADH is associated with dementia in memory clinic patients. However, the hearing ability of patients is often ignored during dementia investigation, and most of the older adults do not report hearing loss due to their compromised cognition, instead it is often perceived as an inconsequential process of aging and thus remains undiagnosed. Conducting a diagnostic hearing assessment in the memory clinic is not feasible due to resource constraints. A simple screening questionnaire such as AIADH would give the physician means to evaluate the effect of hearing impairment on these patients' daily life and plan for further management. Studies have reported that the use of hearing aids has been shown to promote social engagement and improve communication, cognition and emotional function of elderly with hearing loss [51,52]. Furthermore, a recent study in persons with dementia has shown that the use of non-interventional approach such as hearing loss
5. Conclusion Our study showed that hearing handicap is more frequent among patients with dementia than healthy controls despite no significant difference in terms of their peripheral hearing acuity level. The mechanism of this association between hearing handicap and dementia requires further research and may involve higher order auditory dysfunction. We emphasize the need for routine hearing assessment in older people who are at risk of hearing impairment and dementia. This is in view that screening for at risk population in its earliest stages might be useful for therapeutic targets aimed at delaying the progression of disease. Declaration of competing interest All authors declare no conflict of interest regarding this manuscript. Acknowledgement We acknowledge all the Memory Aging & Cognition Centre, National University Hospital coordinators for their contribution to recruitment and data acquisition. Author's contribution BG participated in data acquisition, performed analysis, drafted and revised manuscript. SH, NV and CC were responsible for provided 5
Am J Otolaryngol xxx (xxxx) xxxx
B. Gyanwali, et al.
intellectual advice and revised manuscript. JHYL was responsible for study design and concept, data collection, overall supervision and revised the manuscript.
Gerontol 1986;4(3):3–15. [25] Gates GA, Anderson ML, Feeney MP, McCurry SM, Larson EB. Central auditory dysfunction in older people with memory impairment or Alzheimer’s dementia. Arch Otolaryngol Head Neck Surg 2008;134(7):771–7. [26] Tuwaig M, Savard M, Jutras B, Lamarre-Théroux L, Poirier J, Breitner JCS. Central auditory processing in individuals at risk for Alzheimer's dementia. Alzheimers Dement.11(7):509. [27] Meijer AG, Wit HP, TenVergert EM, Albers FW, Muller Kobold JE. Reliability and validity of the (modified) Amsterdam Inventory for Auditory Disability and Handicap. Int J Audiol 2003;42(4):220–6. [28] Zanchetta S, Simoes HO, Lunardelo PP, Canavezi MO, Reis A, Massuda ET. Crosscultural adaptation of the Amsterdam inventory for auditory disability and handicap to Brazilian Portuguese. (pii: S1808-8694(18)30123-X). Braz J Otorhinolaryngol2018. https://doi.org/10.1016/j.bjorl.2018.07.011. [Epub ahead of print]. [29] Boeschen Hospers JM, Smits N, Smits C, Stam M, Terwee CB, Kramer SE. Reevaluation of the Amsterdam inventory for auditory disability and handicap using item response theory. J Speech Lang Hear Res 2016;59(2):373–83. [30] Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140(6):566–72. [31] Pourhoseingholi MA, Baghestani AR, Vahedi M. How to control confounding effects by statistical analysis. Gastroenterol Hepatol Bed Bench 2012;5(2):79–83. [32] Lee JS, Choi HG, Jang JH, Sim S, Hong SK, Lee H-J, et al. Analysis of predisposing factors for hearing loss in adults. J Korean Med Sci 2015;30(8):1175–82. [33] Lie A, Skogstad M, Johannessen HA, Tynes T, Mehlum IS, Nordby K-C, et al. Occupational noise exposure and hearing: a systematic review. Int Arch Occup Environ Health 2016;89(3):351–72. [34] Hilal S, Ikram MA, Verbeek MM, Franco OH, Stoops E, Vanderstichele H, et al. Creactive protein, plasma amyloid-beta levels, and their interaction with magnetic resonance imaging markers. Stroke 2018;49(11):2692–8. [35] Martin JS, Jerger JF. Some effects of aging on central auditory processing. J Rehabil Res Dev 2005;42(4 Suppl 2):25–44. [36] Gates GA, Beiser A, Rees TS, D’Agostino RB, Wolf PA. Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer’s disease. J Am Geriatr Soc 2002;50(3):482–8. [37] Tuwaig M, Savard M, Jutras B, Poirier J, Collins DL, Rosa-Neto P, et al. Deficit in central auditory processing as a biomarker of pre-clinical Alzheimer’s disease. J Alzheimers Dis 2017;60(4):1589–600. [38] Sinha UK, Hollen KM, Rodriguez R, Miller CA. Auditory system degeneration in Alzheimer’s disease. Neurology 1993;43(4):779–85. [39] Eckert MA, Cute SL, Vaden Jr KI, Kuchinsky SE, Dubno JR. Auditory cortex signs of age-related hearing loss. J Assoc Res Otolaryngol 2012;13(5):703–13. [40] Husain FT, Medina RE, Davis CW, Szymko-Bennett Y, Simonyan K, Pajor NM, et al. Neuroanatomical changes due to hearing loss and chronic tinnitus: a combined VBM and DTI study. Brain Res 2011;1369:74–88. [41] Chang Y, Lee SH, Lee YJ, Hwang MJ, Bae SJ, Kim MN, et al. Auditory neural pathway evaluation on sensorineural hearing loss using diffusion tensor imaging. Neuroreport 2004;15(11):1699–703. [42] Lin Y, Wang J, Wu C, Wai Y, Yu J, Ng S. Diffusion tensor imaging of the auditory pathway in sensorineural hearing loss: changes in radial diffusivity and diffusion anisotropy. J Magn Reson Imaging 2008;28(3):598–603. [43] Lin FR, Ferrucci L, An Y, Goh JO, Doshi J, Metter EJ, et al. Association of hearing impairment with brain volume changes in older adults. Neuroimage 2014;90:84–92. [44] Peelle JE. The hemispheric lateralization of speech processing depends on what “speech” is: a hierarchical perspective. Front Hum Neurosci 2012;6:309. [45] Chetelat G, Landeau B, Eustache F, Mezenge F, Viader F, de la Sayette V, et al. Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage 2005;27(4):934–46. [46] Xipeng L, Ruiyu L, Meng L, Yanzhuo Z, Kaosan G, Liping W. Effects of diabetes on hearing and cochlear structures. J Otol 2013;8(2):82–7. [47] Evans MB, Tonini R, Shope CD, Oghalai JS, Jerger JF, Insull W, et al. Dyslipidemia and auditory function. Otol Neurotol 2006;27(5):609–14. [48] Eckert MA, Kuchinsky SE, Vaden KI, Cute SL, Spampinato MV, Dubno JR. White matter hyperintensities predict low frequency hearing in older adults. J Assoc Res Otolaryngol 2013;14(3):425–33. [49] Bernabei R, Bonuccelli U, Maggi S, Marengoni A, Martini A, Memo M, et al. Hearing loss and cognitive decline in older adults: questions and answers. Aging Clin Exp Res 2014;26(6):567–73. [50] Bagai A, Thavendiranathan P, Detsky AS. Does this patient have hearing impairment? JAMA 2006;295(4):416–28. [51] Maharani A, Dawes P, Nazroo J, Tampubolon G, Pendleton N. Longitudinal relationship between hearing aid use and cognitive function in older Americans. J Am Geriatr Soc 2018;66(6):1130–6. [52] Tsakiropoulou E, Konstantinidis I, Vital I, Konstantinidou S, Kotsani A. Hearing aids: quality of life and socio-economic aspects. Hippokratia 2007;11(4):183–6. [53] Mamo SK, Nirmalasari O, Nieman CL, McNabney MK, Simpson A, Oh ES, et al. Hearing care intervention for persons with dementia: a pilot study. Am J Geriatr Psychiatry 2017;25(1):91–101.
Funding This study was supported by the National Medical Research Council grants; NMRC/CG/NUHS/2010 - R-184-005-184-511, NMRC/CG/013/ 2013, NMRC/CIRG/1446/2016. References [1] Heger I, Deckers K, van Boxtel M, de Vugt M, Hajema K, Verhey F, et al. Dementia awareness and risk perception in middle-aged and older individuals: baseline results of the MijnBreincoach survey on the association between lifestyle and brain health. BMC Public Health 2019;19(1):678. [2] World Health Organization. Dementia Dec [cited 2019 Sept 7]. Available from. http://www.who.int/mediacentre/factsheets/fs362/en/; 2017. [3] Albers MW, Gilmore GC, Kaye J, Murphy C, Wingfield A, Bennett DA, et al. At the interface of sensory and motor dysfunctions and Alzheimer’s disease. Alzheimers Dement 2015;11(1):70–98. [4] Y-m Z, Lu D, L-p L, Zhang H, Y-y Z. Olfactory dysfunction in Alzheimer’s disease. Neuropsychiatr Dis Treat 2016;12:869–75. [5] Huang Q, Tang J. Age-related hearing loss or presbycusis. Eur Arch Otorhinolaryngol 2010;267(8):1179–91. [6] World Health Organization. Prevention of blindness and deafness Geneva [cited 2019 Sept 7]. Avaliable from. http://www.who.int/pbd/deafness/estimates/en/; 2018 Feb. [7] Gates GA, Cobb JL, Linn RT, Rees T, Wolf PA, D’Agostino RB. Central auditory dysfunction, cognitive dysfunction, and dementia in older people. Arch Otolaryngol Head Neck Surg 1996;122(2):161–7. [8] Kramer SE, Kapteyn TS, Festen JM, Tobi H. Factors in subjective hearing disability. Audiology 1995;34(6):311–20. [9] Panza F, Solfrizzi V, Logroscino G. Age-related hearing impairment-a risk factor and frailty marker for dementia and AD. Nat Rev Neurol 2015;11(3):166–75. [10] Adrait A, Perrot X, Nguyen MF, Gueugnon M, Petitot C, Collet L, et al. Do hearing aids influence behavioral and psychological symptoms of dementia and quality of life in hearing impaired Alzheimer’s disease patients and their caregivers? J Alzheimers Dis 2017;58(1):109–21. [11] Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet 2017;390(10113):2673–734. [12] Gold M, Lightfoot L, Hnath-Chisolm T. Hearing loss in a memory disorders clinic: a specially vulnerable population. Arch Neurol 1996;53(9):922–8. [13] Lopes L, Magaldi RM, Gândara MER, Reis AC, Jacob-Filho W. Prevalence of hearing impairment in patients with mild cognitive impairment. Dement Neuropsychol 2007;1(3):253–9. [14] Nirmalasari O, Mamo SK, Nieman CL, Simpson A, Zimmerman J, Nowrangi MA, et al. Age-related hearing loss in older adults with cognitive impairment. Int Psychogeriatr 2017;29(1):115–21. [15] Lin FR, Maas P, Chien W, Carey JP, Ferrucci L, Thorpe R. Association of skin color, race/ethnicity, and hearing loss among adults in the USA. J Assoc Res Otolaryngol 2012;13(1):109–17. [16] Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA. Inequalities in dementia incidence between six racial and ethnic groups over 14 years. Alzheimers Dement 2016;12(3):216–24. [17] Pratt SR, Kuller L, Talbott EO, McHugh-Pemu K, Buhari AM, Xu X. Prevalence of hearing loss in black and white elders: results of the cardiovascular health study. J Speech Lang Hear Res 2009;52(4):973–89. [18] National Population and Talent Division, Strategy Group. Prime Minister's Office Population.sg. Older Singaporeans to double by 2030 Aug 20 [cited 2019 Oct 12] Available from. https://www.population.sg/articles/older-singaporeans-to-doubleby-2030; 2017. [19] Lee JC, Danker AN, Wong YH, Lim MY. Hearing loss amongst the elderly in a Southeast Asian population - a community-based study. Ann Acad Med Singapore 2017;46(4):145–54. [20] Alzhimer'’s Disease International. Dementia in Asia Pacific Region International. Nov [cited 2018 Jul 7] 2014 Available from https://www.alz.co.uk/adi/pdf/ Dementia-Asia-Pacific-2014.pdf. [21] Lin FR, Metter E, O’Brien RJ, Resnick SM, Zonderman AB, Ferrucci L. Hearing loss and incident dementia. Arch Neurol 2011;68(2):214–20. [22] Peters CA, Potter JF, Scholer SG. Hearing impairment as a predictor of cognitive decline in dementia. J Am Geriatr Soc 1988;36(11):981–6. [23] Uhlmann RF, Larson EB, Rees TS, Koepsell TD, Duckert LG. Relationship of hearing impairment to dementia and cognitive dysfunction in older adults. JAMA 1989;261(13):1916–9. [24] Weinstein BE. Hearing loss and senile dementia in the institutionalized elderly. Clin
6