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Hearing impairment in Parkinson's disease: Expanding the nonmotor phenotype
Abstract
The objective of this study was to evaluate hearing impairment in patients affected by Parkinson's disease compared with hearing scores observed in normal age- and sex-matched controls. One hundred eighteen consecutive patients with a clinical diagnosis of Parkinson's disease were screened. Severity of motor symptoms and staging were measured with the Unified Parkinson's Disease Rating Scale (section III) and the Hoehn and Yahr scale. Audiometric evaluation consisted of a comprehensive audiologic case history and questionnaire, visual otoscopic examination, acoustic immittance measures (tympanogram and acoustic reflexes), pure tone audiometry, and measurement of brain stem auditory-evoked potentials. Healthy age- and sex-matched subjects were selected as the control group. One hundred six of 118 patients were enrolled. Pure tone audiometry revealed age-dependent high-frequency hearing loss in patients with Parkinson's disease compared with both normative values and values for healthy age- and sex-matched controls (75/106 [71%], χ2 = 5.959, P = .02; 92/106 [86.8%] vs 60/106 [56.6%], χ2 = 23.804, P < .001, respectively). Pure tone audiometry scores correlated with Hoehn and Yahr scale scores (P < .05). Brain stem auditory-evoked potentials were normal in all patients. Our patients with Parkinson's disease showed age-dependent peripheral, unilateral, or bilateral hearing impairment. Whether these auditory deficits are intrinsic to Parkinson's disease or secondary to a more complex impaired processing of sensorial inputs occurring over the course of illness remains to be determined. Because α-synuclein is located predominately in the efferent neuronal system within the inner ear, it could affect susceptibility to noise-induced hearing loss or presbycusis. It is feasible that the natural aging process combined with neurodegenerative changes intrinsic to Parkinson's disease might interfere with cochlear transduction mechanisms, thus anticipating presbycusis.
... Indeed, essentially all studies have reported an age-related high-frequency hearing impairment in patients with PD based on puretone audiometry. Interestingly, many research groups have demonstrated a further decline of auditory thresholds in patients with PD compared to age-matched healthy controls (HCs), especially in the high-frequency range (e.g., Pisani et al., 2015;Vitale et al., 2012). However, it should be noted that non-differences between patients with PD and HCs regarding auditory thresholds have also been reported (e.g., De Keyser et al., 2019;Richardson and Sussman, information (Figure 2.4). ...
... On the one hand, a number of studies did not find significant differences between patients with PD and agematched healthy controls (HCs) regarding auditory thresholds (Al Jaja et al., 2020;De Keyser et al., 2019;Di Mauro et al., 2017;Lopes et al., 2018;Richardson and Sussman, 2019). On the other hand, several studies have reported significantly increased auditory thresholds or a higher prevalence of hearing impairment in patients with PD compared to age-matched HCs, primarily in the high-frequency range (Al Zarea et al., 2016;Folmer et al., 2017;Hussein and Koura, 2019;Pisani et al., 2015;Scarpa et al., 2020;Shalash et al., 2017;Shetty et al., 2019;Vitale et al., 2012;Yýlmaz et al., 2009). The most generally accepted theory suggests that increased high-frequency auditory thresholds in PD represent the combined effect of agerelated processes (i.e., presbycusis) and the pathophysiological changes intrinsic to PD (Vitale et al., 2012). ...
... On the other hand, several studies have reported significantly increased auditory thresholds or a higher prevalence of hearing impairment in patients with PD compared to age-matched HCs, primarily in the high-frequency range (Al Zarea et al., 2016;Folmer et al., 2017;Hussein and Koura, 2019;Pisani et al., 2015;Scarpa et al., 2020;Shalash et al., 2017;Shetty et al., 2019;Vitale et al., 2012;Yýlmaz et al., 2009). The most generally accepted theory suggests that increased high-frequency auditory thresholds in PD represent the combined effect of agerelated processes (i.e., presbycusis) and the pathophysiological changes intrinsic to PD (Vitale et al., 2012). However, the exact pathophysiological mechanisms underlying this seemingly sensorineural hearing impairment in PD remain elusive. ...
... On the one hand, a number of studies did not find significant differences between patients with PD and age-matched healthy controls (HCs) regarding auditory thresholds (Al Jaja et al., 2020;De Keyser et al., 2019;Di Mauro et al., 2017;Lopes et al., 2018;Richardson & Sussman, 2019). On the other hand, studies have reported significantly higher auditory thresholds or a higher prevalence of hearing impairment in patients with PD compared to age-matched HCs, primarily in the high-frequency range (Al Zarea et al., 2016;Folmer et al., 2017;Hussein & Koura, 2019;Pisani et al., 2015;Scarpa et al., 2020;Shalash et al., 2017;Shetty et al., 2019;Vitale et al., 2016Vitale et al., , 2012Yýlmaz et al., 2009). The most generally accepted theory suggests that increased highfrequency auditory thresholds in PD represent the combined effect of age-related processes (i.e., presbycusis) and the pathophysiological changes intrinsic to PD (Vitale et al., 2012). ...
... On the other hand, studies have reported significantly higher auditory thresholds or a higher prevalence of hearing impairment in patients with PD compared to age-matched HCs, primarily in the high-frequency range (Al Zarea et al., 2016;Folmer et al., 2017;Hussein & Koura, 2019;Pisani et al., 2015;Scarpa et al., 2020;Shalash et al., 2017;Shetty et al., 2019;Vitale et al., 2016Vitale et al., , 2012Yýlmaz et al., 2009). The most generally accepted theory suggests that increased highfrequency auditory thresholds in PD represent the combined effect of age-related processes (i.e., presbycusis) and the pathophysiological changes intrinsic to PD (Vitale et al., 2012). However, the exact pathophysiological mechanisms underlying this seemingly sensorineural hearing impairment in PD remain elusive. ...
... By analogy with motor symptoms in PD, the effect of patients' clinical characteristics on auditory function has also been evaluated. For example, a positive correlation has been reported between measures of disease progression on the one hand and auditory thresholds (Al Zarea et al., 2016;Pisani et al., 2015;Vitale et al., 2016Vitale et al., , 2012 and OAEs on the other hand (Di Mauro et al., 2017). In contrast, other studies did not find significant correlations between disease progression and auditory thresholds (Hussein & Koura, 2019) or OAE signal amplitudes (Pisani et al., 2015). ...
Purpose
Several studies have demonstrated increased auditory thresholds in patients with Parkinson's disease (PD) based on subjective tonal audiometry. However, the pathophysiological mechanisms underlying auditory dysfunction in PD remain elusive. The primary aim of this study was to investigate cochlear and olivocochlear function in PD using objective measurements and to assess the effect of dopaminergic medication on auditory function.
Method
Eighteen patients with PD and 18 gender- and age-matched healthy controls (HCs) were included. Patients with PD participated in medication on and off conditions. Linear mixed models were used to determine the effect of PD on tonal audiometry, transient evoked and distortion product otoacoustic emissions (OAEs), and efferent suppression (ES).
Results
Tonal audiometry revealed normal auditory thresholds in patients with PD for their age across all frequencies. OAE signal amplitudes demonstrated a significant interaction effect between group (PD vs. HC) and frequency, indicating decreased OAEs at low frequencies and increased OAEs at high frequencies in patients with PD. No significant differences were found between patients with PD and HCs regarding ES. In addition, no significant effect of medication status was found on auditory measurements in patients with PD.
Conclusions
Altered OAEs support the hypothesis of cochlear alterations in PD. No evidence was found for the involvement of the medial olivocochlear system. Altogether, OAEs may provide an objective early indicator of auditory alterations in PD and should complement subjective tonal audiometry when assessing and monitoring auditory function in PD.
... In the field of hearing research, alterations in patients with Parkinson's disease were observed in different frequency ranges, although the association with disease features has not been fully defined (Pisani et al., 2015;Folmer et al., 2017;Fradis et al., 1988;Gawel et al., 1981;Shetty et al., 2019;Vitale et al., 2012). Recent studies have also demonstrated impairment in central auditory processing (Folmer et al., 2017) and reduction of distortion-product otoacoustic emission (DPOAE) levels (Pisani et al., 2015), which reflect cochlear outer hair cell (OHC) function. ...
... The difference in audiometric thresholds between patients with Parkinson's disease and controls, by means of PTA testing, is in agreement with previous clinical results (Vitale et al., 2012(Vitale et al., , 2016Shetty et al., 2019, Scarpa et al., 2020. Our results extend previous observations by tackling a large cohort of patients. ...
... Our results extend previous observations by tackling a large cohort of patients. In our study, PTA impairment seems to be present along multiple frequency bands, while in previous studies the extent of frequency involvement varied, possibly due to different sample sizes, experimental settings and patients' clinical and demographic characteristics (Pisani et al., 2015;Vitale et al., 2012Vitale et al., , 2016Shetty et al., 2019). ...
In the last decade, animal studies highlighted the sensitivity of hearing function to lack of specific cochlear dopamine receptors, while several studies on humans reported association between hearing loss and Parkinson’s disease, partially recovered after levodopa administration in de novo patients. Taken together, these observations suggest investigating the possible use of cochlear function outcome variables, particularly, otoacoustic emissions, as sensitive biomarkers of Parkinson’s disease. Any lateralization of hearing dysfunction correlated with Parkinson’s disease lateralization would 1) further confirm their association, and 2) provide a disease-specific differential outcome variable. Differential indicators are particularly useful for diagnostic purposes, because their effectiveness is not limited by physiological inter-subject fluctuations of the outcome variable. Recent advances in the acquisition and analysis techniques of otoacoustic emissions suggest using them for evaluating differential cochlear damage in the two ears.
In this study, we quantitatively evaluated hearing function in a population of subjects with Parkinson’s disease, to investigate the occurrence of hearing loss, and, particularly, whether hearing dysfunction shows lateralization correlated to motor symptoms. Pure tone audiometry and distortion product otoacoustic emissions were used as outcome variables in eighty patients (mean age 65 ± 9 years) and forty-one controls (mean age 64 ± 10 years). An advanced customized acquisition and analysis system was developed and used for otoacoustic testing, which guarantees response stability independent of probe insertion depth, and has the sensitivity necessary to accurately assess the low levels of otoacoustic response typical of elderly subjects.
To our knowledge, this is the first study introducing the distinction between ipsilateral and contralateral ear, with respect to the body side more affected by Parkinson’s disease motor symptoms. Significant asymmetry was found in the auditory function, as both otoacoustic responses and audiometric hearing levels were worse in the ipsilateral ear. Significantly worse hearing function was also observed in patients with Parkinson’s disease compared to controls, confirming previous studies. Several pathophysiological mechanisms may be hypothesized to explain asymmetric cochlear damage in Parkinson's disease, including the impairment of dopamine release and the involvement of extra-dopaminergic circuits, with the cholinergic pathway as a likely candidate.
The observed asymmetry in the audiological response of patients with Parkinson’s disease suggests that lateralization of hearing dysfunction could represent a specific non-motor signature of the disease. The possible diagnostic use of cochlear dysfunction asymmetry as a specific biomarker of Parkinson’s disease deserves further investigation, needing a more precise quantitative assessment, which would require a larger sample size.
... Vertigo (the subjective illusion of environmental motion) and disequilibrium (a disturbance in balance or coordination such that confident ambulation is impaired) are common symptoms in idiopathic Parkinson's disease (PD) and in atypical parkinsonisms such as Multiple System Atrophy (MSA) [1][2][3]. In patients with PD, hearing loss has recently been recognized as an additional non-motor feature [4,5], and vestibular dysfunction has been suggested by a number of studies [6][7][8][9][10]. Conversely, auditory and vestibular functions have been poorly investigated in MSA. ...
... Previous studies have described age-related changes in cVEMP and vHIT characteristics in healthy subjects above 60 years of age [27][28][29][30][31][32]. In the present study, auditory findings in PD patients substantially confirm previous reports of high-frequency age-dependent hearing impairment compared to HC [4,5]. Moreover, we found that disease duration was related to hearing impairment at 2000 and 4000 Hz in patients with PD, suggesting that such dysfunction may worsen with disease progression in addition to age. ...
... Dopamine, which is released from lateral olivocochlear efferent fibers below inner hair cells, plays a significant modulating function on afferent dendrites, thus counteracting glutamate-excitotoxic effects [34,35]. Hence, we could hypothesize that aging in combination with widespread alpha-synuclein neuropathologic changes might interfere with processing of auditory stimuli, thereby contributing to auditory dysfunction [4,5,36]. As a consequence, hearing impairment in PD can be attributed to both peripheral [5,37] and central abnormal auditory processing, including impairment of basal ganglia modulation of auditory inputs [4]. ...
Introduction:
Vertigo and disequilibrium are common symptoms in idiopathic Parkinson's disease (PD) and in Multiple System Atrophy (MSA). Hearing loss has been recently recognized as an additional non-motor feature in PD. The aim of this study is to evaluate audio-vestibular function in patients affected by PD and MSA.
Methods:
Fifteen patients with PD, 16 patients with MSA and 20 age-matched healthy controls (HC) were enrolled. Audio-vestibular examination included pure-tone audiometry (PTA), vestibular bed-side examination, video Head Impulse Test (vHIT), and cervical Vestibular-Evoked Myogenic Potentials (cVEMPs).
Results:
PD and MSA patients showed worse PTA thresholds compared to HC at high frequencies. MSA patients showed worse PTA thresholds at 125 Hz compared to HC. In patients with PD, a direct correlation between disease duration and PTA thresholds was found at 2000 Hz and 4000 Hz. In patients with MSA, disease duration was directly related to PTA thresholds at 125 Hz and 250 Hz. Among PD patients, cVEMPs were absent bilaterally in 46.7% and unilaterally in 13.3% of the subjects. Among MSA patients, cVEMPs were absent bilaterally in 26.7% and unilaterally in 40% of the subjects; p13 latency was significantly increased in PD patients as compared to HC. A significant inverse relationship was found between disease duration and cVEMP amplitude in MSA patients.
Conclusion:
We found that high-frequency hearing loss and cVEMP abnormalities are frequent features of both MSA and PD, suggesting that an audio-vestibular dysfunction may be present in these patients even in the absence of self-reported auditory or vestibular symptoms.
... O estudo mais antigo localizado foi publicado em 1981, 11 havendo mais seis publicações na década de 80 12,13,14,15,16,17, uma na década de 90 18 e três após 2002. 19,20,21 Quanto ao desenho de estudo, em nenhuma das publicações analisadas houve a indicação do tipo de estudo realizado e as informações contidas no item métodos não permitiram a classificação do mesmo. ...
... Entre os critérios de exclusão para a seleção dos sujeitos, a maioria dos estudos consideraram o diagnóstico de outras doenças neurológicas 11,13,14,15,16,17,18,20,21 , doença cardiovascular 11,13,20,21 e doenças do metabolismo 13,14,16,20,21 . ...
... Entre os critérios de exclusão para a seleção dos sujeitos, a maioria dos estudos consideraram o diagnóstico de outras doenças neurológicas 11,13,14,15,16,17,18,20,21 , doença cardiovascular 11,13,20,21 e doenças do metabolismo 13,14,16,20,21 . ...
p class="Normal1" style="text-align: justify;"> Introdução : A doença de Parkinson (DP) é uma enfermidade neurodegenerativa associada ao envelhecimento. Os comprometimentos auditivos, embora frequentes em idosos, não são claramente estabelecidos na doença. Objetivo : Identificar a presença de processos fisiopatológicos na condução neural das vias auditivas aferentes na DP. Método : Trata-se de uma revisão sistemática, conduzida a partir da identificação de estudos nas bases de dados PUBMED, Web of Science, SCOOPUS, MEDLINE, LILACS, SciELO e Cochrane, utilizando a combinação dos termos Parkinson’s disease , hearing , auditory perception , hearing disorders , hearing tests , auditory processing e auditory evoked potentials . Foram incluídos artigos em inglês, português ou espanhol que investigaram os Potenciais Evocados Auditivos do Tronco Encefálico (PEATE) em sujeitos com DP. Realizou-se a descrição dos resultados e análise da qualidade metodológica dos estudos. Resultados : Dos 622 artigos identificados, foram selecionados 11 estudos publicados entre 1981 e 2012. Em sete estudos foi verificado prolongamento das latências do PEATE nos sujeitos com DP em relação aos controles. Por outro lado, em quatro investigações as respostas dos sujeitos com DP foram classificadas como normais. Verificou-se fragilidades no delineamento metodológico dos estudos analisados quanto à seleção dos sujeitos, acurácia da exposição, determinação do desfecho principal e controle de variáveis confundidoras. Conclusão : A presença de alterações na condução neuroeletrofisiológica na DP é controversa, havendo necessidade de estudos conduzidos com maior rigor metodológico quanto ao desfecho de análise, seleção dos sujeitos e controle de variáveis confundidoras. O presente estudo contribui com informações que podem favorecer decisões metodológicas para o desenvolvimento de investigações futuras sobre o tema. </p
... However, a better comprehension of the underling mechanisms is crucial to conceive novel therapeutic options for patients. Recent evidence included hearing loss into the wide spectrum of PD NMS [4]. The origin of hearing loss in PD has not been clarified yet; indeed it may be related to the physiological hypoacusis of aging, reaching 62% of population at the age of 85 [5]. ...
... The PD group, by history, showed a mean disease duration of 8.7 ± 1.1 years and, on clinical examination, a mean UPDRS III score of 9.64 ± 5.6 (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], H&Y staging ranged from 1.5 to 3 (mean 2.4 ± 1.2). ...
... The ART group showed a mean disease duration of 8.4 ± 1.3 years and a mean UPDRS III score of 9.25 ± 6.2 (range, [4][5][6][7][8][9][10][11][12][13][14] with an H&Y staging ranged from 1 to 2 (mean 1.2 ± 1.1). ...
Background and objective: Non-motor symptoms (NMS) of Parkinson's disease (PD) are still underestimated and causative of disability and poor quality of life. Recently, it has been suggested that hearing impairment could be included into the spectrum of NMS, although both mechanisms and phenomenology are unclear. In this study we investigated the peripheral auditory pathway of PD, in patients with asymmetric rest tremor (ART) without dopaminergic denervation, and comparison with healthy controls (HC), aiming to detect differential alterations of cochlear functioning and medial olivocochlear system (MOC).Methods: 23 PD patients, 9 with ART and 19 HC were assessed for auditory functions with clinical examination and Transient-evoked otoacoustic emissions (TEOAEs). PD and ART groups were also evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) II-III and Hoehn and Yahr scale. One-way ANOVA analysis and Pearson's test were performed to measure differences between groups and correlations.Results: TEOAE responses in PD patients were significantly lower compared to HC at 3 and 4 kHz, bilaterally. PD patients showed statistically significant lower TEOAEs at the same frequencies compared to ARTs. In addition, a MOC dysfunction in PD patients was observed. Conversely, no difference was found between ART and HC in all tests performed.Conclusion: PD patients, differently from both ART patients and HC, show abnormalities of basal TEOAEs at the highest frequencies. Auditory dysfunction correlates to motor disturbances, suggesting an underlying dopaminergic pathogenic mechanism. Early recognition of hearing impairment may represent a tool for patient assessment and help in the differential diagnosis in ART patients.
... Previous studies by Yýlmaz et al. [14], Vitale et al. [15], Lai et al. [16], and Pisani et al. [17] reported greater hearing loss in PD patients compared to control groups without PD. ...
... In this study, PD patients and control subjects both exhibited a pattern of high-frequency hearing loss which is typical for their age [3,4]. These results are similar to those reported by Vitale et al. [15] in a study of 106 PD patients. ...
... Results of the current study and those reported by Guehl et al. [18], Lewald et al. [19], and Vitale et al. [20] indicate impaired neural processing of auditory stimuli by PD patients. Several factors probably contribute to these central auditory processing (CAP) deficits, including aging, hearing loss, and degeneration/dysfunction of neural structures and pathways related to the pathophysiology of PD [15]. While these factors cannot yet be stopped or reversed, their negative effects on central auditory processing might be minimized or slowed by implementing effective and appropriate aural rehabilitation strategies, which may include the following: ...
Since Parkinson’s Disease (PD) primarily affects older people, a majority of PD patients have age-related hearing loss (HL) that will worsen over time.The goal of this study was to assess peripheral and central auditory functions in a population of PD patients and compare the results with a group of age-matched control subjects. Study participants included 35 adults with PD (mean age = 66.9 ± 11.2 years) and a group of 35 healthy control subjects (mean age = 65.4 ± 12.3 years). Assessments included questionnaires, neuropsychological tests, audiometric testing, and a battery of central auditory processing tests. Both study groups exhibited patterns of sensorineural hearing loss (slightly worse in the PD group) which were typical for their age and would contribute to difficulties in communication for many participants. Compared to the control group, PD patients reported greater difficulty in hearing words people are speaking. Although 27 PD patients (77%) were good candidates for amplification, only 7 (26%) of these hearing aid candidates used the devices. Because it is important for PD patients to optimize communication with their family members, caregivers, friends, and clinicians, it is vital to identify and remediate auditory dysfunction in this population as early as possible.
... Alterations in auditory processing have been especially frequently described in PD patients (for a recent review, see [24]). Patients with PD have been demonstrated to suffer from impaired hearing compared with age-matched healthy control subjects (e.g., [25]), and a previous MEG study suggested changes in the cortical processing of auditory information in PD patients without DBS [26]. DBS was subsequently shown to enhance the strength of the most prominent auditory evoked fields (AEFs) at~100 ms after stimulus onset (N100m) [18], but the possible long-term modulation of auditory cortical responses by DBS has not been reported before. ...
... Earlier AEF studies have suggested a direct auditory cortical disruption by PD (e.g., [26]), possibly related to basal ganglia dysfunction together with the emphasized sensorineural hearing loss in PD [25]. Furthermore, local field potentials recorded from the STN are correlated with spontaneous~10-Hz oscillatory activity over the auditory temporal cortices [45,46]. ...
Deep brain stimulation (DBS) has proven its clinical efficacy in Parkinson’s disease (PD), but its exact mechanisms and cortical effects continue to be unclear. Subthalamic (STN) DBS acutely modifies auditory evoked responses, but its long-term effect on auditory cortical processing remains ambiguous. We studied with magnetoencephalography the effect of long-term STN DBS on auditory processing in patients with advanced PD. DBS resulted in significantly increased contra-ipsilateral auditory response latency difference at ~100 ms after stimulus onset compared with preoperative state. The effect is likely due to normalization of neuronal asynchrony in the auditory pathways. The present results indicate that STN DBS in advanced PD patients has long-lasting effects on cortical areas outside those confined to motor processing. Whole-head magnetoencephalography provides a feasible tool to study motor and non-motor neural networks in PD, and to track possible changes related to cortical reorganization or plasticity induced by DBS.
... Several previous studies have assessed the diagnostic utility of BAER in PD, reporting contradictory results. Some studies have shown normal BAER latencies [25,34], while others have demonstrated prolonged latencies of BAER in PD [2,5,18,[27][28][29]33,35].The accumulation of alpha-synuclein in different parts of the brain, mainly the brainstem, with disease progression in PD leads to neuronal dysfunction and subsequent neuronal death [14].Although clinical manifestations of DIP are similar to PD to a large extent, the two conditions have distinct pathophysiological mechanisms [19].We hypothesized that BAER latencies, particularly those related to brain stem function, will therefore be normal in patients with DIP, and prolonged in those with PD, and that BAER could therefore be a valuable diagnostic tool for differentiating DIP from PD. ...
... We demonstrated that wave V latencies and I-V and III-V IPLs were significantly prolonged in PD patients compared to normal individuals and the DIP group. Our findings were consistent with the results of previous studies [2,5,18,27À29,33,35], although other shave reported normal BAER latencies in PD [25,34].The clinical heterogeneity of patients with PD may explain these differences [29]. Jellinger [14]suggested progressive accumulation of alpha-synuclein in both dopaminergic and non-dopaminergic neurons in the brain stem of PD patients, leading to neurodegeneration/inflammation and loss of functionality of these neurons, with a positive correlation between disease duration and severity of neurodegeneration. ...
Objectives
Brainstem auditory evoked response (BAER) is a non-invasive modality that can be used to investigate brainstem neuronal function in movement disorders. The differentiation between drug-induced parkinsonism (DIP) and Parkinson's disease (PD) can be very challenging. Although PD and DIP to some extent display similar clinical symptoms, the underlying pathophysiologic mechanisms are entirely different. Given these differences in pathogenesis, and the diagnostic utility of BAER for detecting brainstem function, BAER may help to distinguish between PD and DIP. This study aimed to assess the accuracy and predictive values of BAER parameters in differentiating DIP from PD.
Methods
We prospectively studied143 participants classified within three groups, including 50 controls, 57 PD, and 36 DIP. BAER was performed on all patients in the study. Patients in the DIP group were followed up for at least one year after discontinuation of the causative drug and examined for final diagnosis. We compared BAER latencies of the three groups and measured sensitivity, specificity, predictive values, likelihood ratios, and accuracy of BAER in diagnosing DIP.
Result
Waves V, I-V, and III-V latencies were significantly prolonged among the PD patients compared to the DIP and the control group; however, there were no significant differences in BAER latencies between the DIP and the control group. Waves V and I-V latencies revealed the highest accuracy (86% and 79%, respectively) in distinguishing DIP from PD with high negative predictive value(89% and 83%, respectively) as well as a high negative likelihood ratio (0.2and 0.3, respectively).
Conclusion
This study showed that waves V and I-V latencies are significantly prolonged in PD patients compared to those with DIP, consistent with the proposed mechanisms of neurodegeneration in PD, particularly in the midbrain and pons. Consequently, BAER could be used as a useful diagnostic tool for differentiating DIP from PD.
... Guehl et al. [8], Lewald et al. [9], and Vitale et al. [10] reported that PD patients exhibited poorer performance on behavioral assessments of auditory processing compared to groups of age-matched, healthy control subjects. Therefore, the neuropathological mechanisms of PD appear to contribute to central auditory processing (CAP) deficits in this population [11]. A previous study by our research group also reported abnormal performance by a group of PD patients on behavioral CAP tests [12]. ...
... Red: control group response to nontarget digits; Green: PD group response to nontarget digits; Blue: PD group response to target digits; Yellow: control group response to target digits. [11] in a study of 106 PD patients. In that study, the PTA threshold for audiometric frequencies 0.5, 1, 2, and 4 kHz was 26 dB HL for the entire patient group, with greater degrees of hearing loss exhibited by older subgroups of participants. ...
Background. Parkinson’s disease (PD) patients are at increased risk for central auditory processing (CAP) deficits and cognitive dysfunction. However, behavioral assessments of CAP and cognitive processing used in a previous study by our research team found few significant differences in performance between early-stage PD patients and age-matched control subjects. The objective of this study is to use auditory event-related potentials (AERPs) to compare CAP and cognitive functions in a population of PD patients with a group of age-matched control subjects. Methods. AERPs in response to tonal and speech stimuli were recorded from 35 adults who had a medical diagnosis of PD (23 males and 12 females; ), and 35 age-matched control subjects who did not have PD or any other neurological disorders (31 males and 4 females; ). Auditory stimuli included pure tones (500 and 1000 Hz) to elicit the P300 response and a dichotic digits paradigm to elicit the N200 processing negativity. Results. Compared to control subjects, PD patients exhibited significantly longer latencies of P300 and N200 components and smaller amplitude N200 components. Latency and amplitude of the N200 component were significantly correlated with participants’ age. N200 amplitude was correlated with results from the Rey Auditory Verbal Learning Test (RAVLT) of cognitive ability. Latency of the P300 and amplitude of the N200 components were significantly correlated with results from the Spatial Release From Masking (SRM) behavioral CAP assessment. Conclusions. AERP assessments used in this study appear to be sensitive indicators of CAP and cognitive deficits exhibited by early-stage PD patients. While few significant differences in performance on behavioral CAP and cognitive tests were previously observed between this population of PD patients and age-matched control subjects, N200 and P300 components recorded in the present study revealed impaired neural processing by the PD group.
1. Introduction
Aging and hearing loss both contribute to declines in one’s ability to process auditory information. For example, older people and those with hearing loss often have difficulty understanding conversational speech when background noise is present [1–3]. The average patient age for Parkinson’s disease (PD) onset is approximately 60 years, and the prevalence of PD increases with age [4]. Since the majority of people 60 years old and older have significant hearing loss (HL), and the prevalence of HL increases with age [5, 6], a majority of PD patients have significant HL that will worsen over time. Patients with untreated hearing loss dedicate more of their resources to auditory perceptual processing to the detriment of other cognitive processes. Therefore, hearing loss may contribute to dementia through exhaustion of cognitive reserves, social isolation, sensory deafferentation, or a combination of these mechanisms [7]. Since cognitive decline and dysfunction are common sequelae of PD [4], untreated hearing loss is likely to exacerbate cognitive deficits that are experienced by many PD patients.
Guehl et al. [8], Lewald et al. [9], and Vitale et al. [10] reported that PD patients exhibited poorer performance on behavioral assessments of auditory processing compared to groups of age-matched, healthy control subjects. Therefore, the neuropathological mechanisms of PD appear to contribute to central auditory processing (CAP) deficits in this population [11]. A previous study by our research group also reported abnormal performance by a group of PD patients on behavioral CAP tests [12]. However, because most of these PD patients were in the early and less severe stages of disease, their performance on many CAP assessments did not differ significantly from that exhibited by a group of age-matched healthy control subjects.
The goal of the present study was to use auditory event-related potentials (AERPs) to assess CAP and cognitive functions in a population of PD patients and compare the results with a group of age-matched control subjects without PD or other neurological disorders. We hypothesized that electrophysiological recordings are more sensitive detectors of auditory and cognitive processing deficits exhibited by PD patients than are the behavioral assessments used in our previous study [12].
2. Methods
All procedures for the conduct of the study adhered to the requirements of the Institutional Review Board at VA Portland Medical Center, where the study was conducted.
Participants included 35 adults who had a medical diagnosis of PD and 35 age-matched control subjects who did not have PD or any other neurological disorders. All of the participants in this study were the same as those in our 2017 publication [12]. Also, the electrophysiological data reported in this article were collected around the same time as behavioral data previously reported for this population [12].
After written informed consent was obtained, participants underwent the procedures and assessments described below over the course of three sessions.
2.1. Assessments of PD Severity
The Hoehn and Yahr [13] and Schwab and England [14] scales were used to assess the stage and severity of PD for individuals in the patient group.
Parkinson patients were also asked to rate their abilities “during the past week” for 12 activities such as swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (these questions were taken from Part II of the Unified Parkinson’s Disease Rating Scale [15]).
2.2. Neuropsychological Evaluation
The Rey Auditory Verbal Learning Test (RAVLT) [16] was administered to all study participants. This test evaluates a variety of functions: short-term auditory-verbal memory, rate of learning, learning strategies, retroactive and proactive interference, presence of confabulation or confusion in memory processes, retention of information, and differences between learning and retrieval. Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat them. Another list of 15 unrelated words is given, and the subject must then repeat the original list of 15 words; this process is repeated again 30 minutes later.
2.3. Comprehensive Audiometric Evaluation
Pure tone air and bone conduction thresholds were measured in each ear using procedures recommended by the American Speech-Language-Hearing Association [17].
2.4. Assessments of Central Auditory Processing (CAP)
Several different CAP evaluations were administered to study participants: Staggered-Spondaic-Word (SSW) test [18], Masking-Level Difference (MLD) Test [19, 20], Gap in Noise (GIN) Detection Test [21], Dichotic Digits Test [22], Spatial Release From Masking (SRM) tests [23], and Speech Intelligibility in Noise was assessed using the Words in Noise (WIN) test [24]. These tests are described in our previous publication involving this study population [12].
2.5. Electrophysiological Recordings of Auditory Event-Related Potentials (AERPs)
Long-latency AERPs were recorded from 15 Ag/AgCl scalp electrodes using a Quik Cap and a Neuroscan EEG/EP system (Compumedics, Charlotte, NC) according to parameters described in Papesh et al. [25]. Responses to 50 repetitions of each stimulus were averaged to create individual responses within each condition. Grand average responses were created for each condition and group.
Latency and amplitude values of N100, P200, N200, and P300 components were determined by the agreement of the three judges. Long-latency AERPs were recorded from each subject in response to the following stimuli which were presented via Etymotic ER-3 insert earphones (Etymotic Research, Inc.; Elk Grove Village, IL).
2.5.1. “Oddball” Paradigm (Tones) to Elicit P300 Responses
Stimuli: 50 1000-Hz tones (100 msec duration) and 200 500-Hz tones (100 msec duration) were presented in a randomized sequence at 85 dB SPL to each ear monaurally; . Task: subjects counted higher-pitched (1000 Hz) tones silently to themselves. This electrophysiological protocol provides an objective measure of central auditory processing and cognitive function.
2.5.2. Dichotic Digits
Stimuli: an assortment of 300 spoken digits (50 each: 1, 2, 3, 4, 5, or 6) delivered dichotically and presented randomly. Task: subjects pushed a button with their right index finger when they heard the target “four” in either ear. Because a study by Lewald et al. [9] reported that PD patients exhibited deficits in behavioral dichotic listening tasks, this electrophysiological protocol was included to provide an objective measure of neural processing and cognitive function during such a task.
2.6. Data Analysis
Mean and standard deviation values were calculated for each assessment, AERP component, and study group. Between-group comparisons were conducted using 2-tailed -tests and applying appropriate Bonferroni corrections as needed. Pearson correlation calculations were also made in certain instances as indicated in the Results section. Tests of normality and homogeneity of variances confirmed the statistical appropriateness of these analyses for the data collected.
3. Results
3.1. Participant Characteristics
The PD group consisted of 35 adults (23 males and 12 females; ). The control group also consisted of 35 adults (31 males and 4 females; ) who had no history of PD or other neurological disorders. The difference in the proportion of males vs. females in each of the study groups was statistically significant (). Levodopa use by PD patients: all PD patients except one used levodopa medication daily—he had not yet started using this medication. Of 105 total appointments, PD patients reported that they were “on” the effects of levodopa for 95 appointments, “off” for 7 appointments, and “in-between” for 3 appointments.
For additional details about participant characteristics, see our previous publication involving this study population [12].
3.1.1. Ratings of Daily Activity Abilities
For PD patients in this study, the total score on these 12 questions ranged from 3 to 27 (), with higher scores indicating greater difficulty on the collection of tasks. These data, combined with Hoehn and Yahr and Schwab and England results, suggest that the majority of PD patients in this study were in the early—or less severe—stages of the disease.
3.2. Neuropsychological Evaluation
Mean RAVLT scores (total of trials 1 through 5) were for PD patients and for control subjects, which indicates normal performance for the age and education level of study participants [26]. The difference in mean scores between study groups was not statistically significant. Also, there was no statistically significant difference in the number of intrusions or repetitions made by the two study groups on this test.
3.3. Pure Tone Audiometry
Pure-tone audiometry indicated that both the control and PD groups had sloping, high-frequency sensorineural hearing loss which is typical for their age range (see Figure 1 in Folmer et al. [12]). Compared to age-matched healthy control subjects, PD patients exhibited worse hearing sensitivity for 1500 and 2000 Hz test frequencies. Pure tone average (PTA) threshold was HL for the control group and HL for the PD group.
We subdivided study participants into younger (≤65 years) and older (>65 years) groups according to age criteria used by da Silva Lopes et al. [27]. This grouping resulted in 19 younger () and 16 older () control subjects; 17 younger () and 18 older () PD patients. In general, hearing sensitivity for older participants (older controls = OC; older Parkinson = OP) was worse compared to younger participants (younger controls = YC; younger Parkinson = YP), especially for higher frequencies. Pure tone hearing thresholds did not differ significantly between the OC and OP groups. However, the younger PD group exhibited worse hearing between 1500 and 2000 Hz compared to the younger control group. This difference was the major contributor to overall differences in hearing sensitivity between the entire PD and control groups.
3.4. Assessments of Central Auditory Processing
As reported in our previous publication involving this study population [12], both study groups exhibited deficits in many assessments of central auditory processing (CAP), with PD patients performing significantly worse than the control group on the Spatial Release from Masking (SRM) 45° test condition only. Compared to the control group performance on the SRM test, the PD group had greater difficulty understanding sentences in a background of competing speech, and they also showed less improvement on this task when the target and competing sentences were separated in space (the 45° condition).
3.5. Electrophysiological (AERP) Results
3.5.1. “Oddball” Protocol to Elicit the P300 Response
As shown in Figure 1, AERP grand averaged responses to the “nontarget” 500 Hz tones (recorded at electrode Cz) were basically the same for PD patients and control subjects. The latency and amplitude of the N100 component are not significantly different between the study groups. However, the mean latency of the P300 component in response to the “target” 1000 Hz tones was significantly delayed () for PD patients () compared to control subjects (). There was no statistically significant difference in P300 amplitude between the PD and control groups.
... Since this was not the case in the visual modality, in which patients responded as quickly as controls, this slowness responding to auditory stimuli suggests that patients have hearing loss, compared with age-matched controls. Specific hearing loss has recently been recognized as an additional nonmotor feature in patients with PD (Vitale et al., 2012), even in de novo patients (Pisani et al., 2015). From a pathophysiological point of view, the natural aging process, combined with the intrinsic neurodegenerative changes in PD, could interfere with cochlear transduction mechanisms, contributing to presbycusis (Vitale et al., 2012). ...
... Specific hearing loss has recently been recognized as an additional nonmotor feature in patients with PD (Vitale et al., 2012), even in de novo patients (Pisani et al., 2015). From a pathophysiological point of view, the natural aging process, combined with the intrinsic neurodegenerative changes in PD, could interfere with cochlear transduction mechanisms, contributing to presbycusis (Vitale et al., 2012). However, we did not specifically measure participants' hearing acuity, and further research is required to elucidate the involvement of an auditory perceptual deficit in PD in higher-order language processes. ...
Introduction:
Although the motor signs of Parkinson's disease (PD) are well defined, nonmotor symptoms, including higher-level language deficits, have also been shown to be frequent in patients with PD. In the present study, we used a lexical decision task (LDT) to find out whether access to the mental lexicon is impaired in patients with PD, and whether task performance is affected by bradykinesia.
Materials and methods:
Participants were 34 nondemented patients with PD, either without (off) medication (n = 16) or under optimum (on) medication (n = 18). A total of 19 age-matched control volunteers were also recruited. We recorded reaction times (RTs) to the LDT and a simple RT (control) task. In each task, stimuli were either visual or auditory. Statistical analyses consisted of repeated-measures analyses of variance and Tukey's HSD post hoc tests.
Results:
In the LDT, participants with PD both off and on medication exhibited intact access to the mental lexicon in both modalities. In the visual modality, patients off medication were just as fast as controls when identifying real words, but slower when identifying pseudowords. In the visual modality of the control task, RTs for pseudowords were significantly longer for PD patients off medication than for controls, revealing an unexpected but significant lexicality effect in patients that was not observed in the auditory modality. Performances of patients on medication did not differ from those of age-matched controls.
Discussion:
Motor execution was not slowed in patients with PD either off or on medication, in comparison with controls. Regarding lexical access, patients off medication seemed to (1) have difficulty inhibiting a cognitive-linguistic process (i.e., reading) when it was not required (simple reaction time task), and (2) exhibit a specific pseudoword processing deficit in the LDT, which may have been related to impaired lateral word inhibition within the mental lexicon. These deficits seemed to be compensated by medication.
... Our results regarding the association between peripheral HL (based on the PTA) and pure LBCI are consistent with previous studies showing that patients with PD have peripheral HL. 29,30 A previous study suggested that α-synuclein located in the cochlea and stria vascularis 31 is related to and plays a role in susceptibility to noise-induced peripheral HL. 29 Another study found that cochlear function was restored after dopamine treatment, and suggested that the depletion of dopamine in the olivocochlear system could expose primary auditory neurons to excessive glutamate release from inner hair cells that results in peripheral HL. 30 Future studies of the correlation between the severities of nigrostriatal dopamine depletion and HL are warranted to determine if there is further support for this hypothesis. ...
... Our results regarding the association between peripheral HL (based on the PTA) and pure LBCI are consistent with previous studies showing that patients with PD have peripheral HL. 29,30 A previous study suggested that α-synuclein located in the cochlea and stria vascularis 31 is related to and plays a role in susceptibility to noise-induced peripheral HL. 29 Another study found that cochlear function was restored after dopamine treatment, and suggested that the depletion of dopamine in the olivocochlear system could expose primary auditory neurons to excessive glutamate release from inner hair cells that results in peripheral HL. 30 Future studies of the correlation between the severities of nigrostriatal dopamine depletion and HL are warranted to determine if there is further support for this hypothesis. ...
Background and purpose:
The associations between hearing loss (HL) and the mechanisms underlying cognitive impairment (CI) remain unclear. We evaluated the effects of clinical factors, vascular magnetic resonance imaging (MRI) markers, and CI mechanisms on HL.
Methods:
In total, 112 patients with CI (59% demented) and subjective HL prospectively underwent MRI, amyloid positron-emission tomography (PET), hearing evaluations, and neuropsychological tests including a language comprehension test. Patients were categorized into pure-Alzheimer's disease-related CI (ADCI), pure-Lewy-body disease-related CI (LBCI), mixed-ADCI/LBCI, and non-ADCI/LBCI groups based on clinical features and PET biomarkers.
Results:
The risk of peripheral HL [defined as a pure-tone average (PTA) threshold >40 dB] was higher in the pure-LBCI group than in the pure-ADCI and mixed-ADCI/LBCI groups, and lower in the presence of ADCI. The non-ADCI/LBCI group had the most-severe vascular MRI markers and showed a higher risk of peripheral HL than did the pure-ADCI and mixed-ADCI/LBCI groups. While the pure-LBCI group had a higher risk of comprehension dysfunction than the pure-ADCI group regardless of the PTA and the score on the Korean version of the Mini Mental State Examination (K-MMSE), those in the pure-LBCI group even with a better K-MMSE score had a risk of comprehension dysfunction comparable to that in the mixed-ADCI/LBCI group due to a worse PTA.
Conclusions:
Peripheral HL could be associated with the absence of significant β-amyloid deposition in patients with CI and characteristic of the pure-LBCI and non-ADCI/LBCI groups.
... These studies did not find significant differences between patients with PD and HCs regarding pure-tone hearing thresholds. On the other hand, higher pure-tone hearing thresholds in patients with PD have been reported by other research groups in the middle to high frequency range (1.5-8 kHz) (21)(22)(23)(24)(25)(26)(27)(28). The differences between study results may be influenced by the approach chosen to analyze the data (e.g., categorical vs. continuous data-analysis, consideration of confounding variables, correction for multiple comparisons). ...
... The involvement of the peripheral auditory system in PD has generally been regarded as an age-dependent sensorineural dysfunction (i.e., presbycusis) (23,27). Structural changes underlying presbycusis include loss of cochlear hair cells, which in turn, affects afferent transmission of auditory information to higher auditory structures (145). ...
Research on auditory processing in Parkinson's disease (PD) has recently made substantial progress. At present, evidence has been found for altered auditory processing in the clinical stage of PD. The auditory alterations in PD have been demonstrated with low-cost and non-invasive assessments that are already used in routine clinical practice. Since auditory alterations have been reported early in disease progression, it would be highly relevant to investigate whether auditory markers could be provided in the prodromal stage of PD. In addition, auditory alterations in early stage PD might be modulated by dopaminergic medication. Therefore, the aim of this review is (1) to summarize the literature on auditory processing in PD with a specific focus on the early disease stages, (2) to give future perspectives on which audiological and electrophysiological measurements could be useful in the prodromal stage of PD and (3) to assess the effect of dopaminergic medication on potential auditory markers in the prodromal stage of PD.
... A large number of studies have demonstrated an association between hearing loss and neurodegenerative diseases [21][22][23][24][25][26][27][28][29][30][31][32][33]. Hearing loss is a risk marker for cognitive decline and dementia [23]. ...
... The reverse causality might be possible between dementia and hearing impairment [25,26]. Previous studies also reported greater hearing loss and impaired auditory processing in PD patients [27,28]. However, according to another approach, similar patterns of sensorineural hearing loss (slightly worse in the PD group) were observed when comparing the control group and PD patients, which were typical for their age [29]. ...
Background: Essential tremor (ET) is the most common adult movement disorder, characterized by several
motor and increasingly well recognized non-motor symptoms. Sensory deficits, such as hearing impairment
and olfactory dysfunction, are amongst them. This review analyzes the available evidence of these sensory
deficits and their possible mechanistic basis in patients with ET.
Method: A PubMed literature search on the topic was performed in the May 2019 database.
Results: Nineteen articles on hearing impairment and olfactory dysfunction in ET patients were identified.
The prevalence of hearing impairment is higher in ET patients than healthy controls or Parkinson disease.
Cochlear pathologies are suggested as the underlying cause, but there is still a lack of information about
retrocochlear pathologies and central auditory processing. Reports on olfactory dysfunction have conflicting
results. The presence of mild olfactory dysfunction in ET was suggested. Conflicting results may be due to
the lack of consideration of the disease’s heterogeneity, but according to recent data, most studies do not
find prominent evidence of olfactory loss in ET.
Conclusion: Although there is increasing interest in studies on non-motor symptoms in ET, there are few
studies on sensory deficits, which are of particularly high prevalence. More studies are needed on to investigate the basis of non-motor symptoms, including sensory deficits.
Keywords: essential tremor; non-motor features; sensory deficit; hearing impairment; olfactory dysfunction;
neurodegenerative disease
... Evidence for a peripheral involvement primarily comes from studies using subjective pure tone audiometry. In PD, a greater worsening of high-frequency auditory thresholds based on age has been reported (Folmer et al., 2017;Pisani et al., 2015;Scarpa et al., 2020;Shalash et al., 2017;Vitale et al., 2012Vitale et al., , 2016Yýlmaz et al., 2009). In contrast, other authors found normal auditory thresholds in patients with PD for their age (De Keyser et al., 2019;Di Mauro et al., 2017). ...
... All studies used a monaurally presented click stimulus at a presentation rate of approximately 10/ second. Three of these studies reported no significant differences between patients with PD and HCs regarding ABR peak latencies and/or interpeak latencies (IPLs) (Karayanidis et al., 1995;Muthane et al., 1993;Vitale et al., 2012). ...
Altered auditory processing has been increasingly recognized as a non-motor feature in parkinsonian disorders. This systematic review provides an overview of behavioral and electrophysiological literature on central auditory processing in patients with Parkinson’s disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A systematic database search was conducted and yielded 88 studies that met the intelligibility criteria. The collected data revealed distinct impairments in a range of central auditory processes in PD, including altered deviance detection of basic auditory features, auditory brainstem processing, auditory gating and selective auditory attention. In contrast to PD, literature on central auditory processing in MSA and PSP was relatively scarce, but provided some evidence for impaired central auditory processing in MSA and PSP. The interpretation of these findings is discussed and suggestions for further research are offered.
... 14,15 In recent decades, there is also extensive evidence that supports a general dysfunction of the auditory system in PD. Studies indicate a broad spectrum of auditory impairments in PD, ranging from peripheral hearing impairments at the cochlear level [16][17][18] through the low 19,20 and high auditory brainstem (BS) [21][22][23][24][25][26] to cortical auditory areas. 11,[27][28][29][30][31] A few studies also demonstrate improvement in auditory behavioral findings 32,33 or electrophysiological results 18,[34][35][36] following dopaminergic therapy, which implicates similarities in neurotransmitters of the auditory system and basal ganglia. ...
... These findings suggest that hearing loss in PD is, at least partly, independent of presbycusis. There are multiple studies in PD that show the increase of audiometric hearing thresholds (after adjustment for the effect of ARHL), 17,18,22,40,41 abnormality of acoustic startle reflex (ASR), 19,20,42 and prolongation of auditory reaction time [43][44][45] as various indications of impairment in the peripheral auditory system (PAS; i.e., the cochlea and auditory nerve). There are also several psychoacoustic studies in PD that account for disorders of auditory temporal processing, 33,43,[46][47][48][49] which are ameliorated with dopaminergic treatment 33 or DBS of the STN. ...
PD is a progressive and complex neurological disorder with heterogeneous symptomatology. PD is characterized by classical motor features of parkinsonism and nonmotor symptoms and involves extensive regions of the nervous system, various neurotransmitters, and protein aggregates. Extensive evidence supports auditory dysfunction as an additional nonmotor feature of PD. Studies indicate a broad range of auditory impairments in PD, from the peripheral hearing system to the auditory brainstem and cortical areas. For instance, research demonstrates a higher occurrence of hearing loss in early‐onset PD and evidence of abnormal auditory evoked potentials, event‐related potentials, and habituation to novel stimuli. Electrophysiological data, such as auditory P3a, also is suggested as a sensitive measure of illness duration and severity. Improvement in auditory responses following dopaminergic therapies also indicates the presence of similar neurotransmitters (i.e., glutamate and dopamine) in the auditory system and basal ganglia. Nonetheless, hearing impairments in PD have received little attention in clinical practice so far. This review summarizes evidence of peripheral and central auditory impairments in PD and provides conclusions and directions for future empirical and clinical research. © 2020 International Parkinson and Movement Disorder Society
... A small number of studies have implicated peripheral and central auditory involvement in persons with PD, which extend beyond the age-related changes in audition reported for healthy older adults (Lai, Liao, Lin, Lin, & Sung, 2014;Pisani et al., 2015;Vitale, Marcelli, Allocca, & Barone, 2012). While focal deficits in pitch variability (Miranda, Pereira, Bommarito, & Silva, 2004) and temporal processing (Merchant, Luciana, Hooper, Majestic, & Tuite, 2008;Pastor, Artieda, Jahanshahi, & Obeso, 1992) have been identified for persons with PD, disease-related changes in loudness perception are not well understood. ...
... There is evidence to suggest that persons with PD experience sensory limitations in the areas of olfaction (Doty, 2012;Shah et al., 2009), vision (Armstrong, 2011;M. Price, Feldman, Adelberg, & Kayne, 1992), proprioception (Rabin, Muratori, Svokos, & Gordon, 2010), and peripheral and central auditory function (Lai et al., 2014;Pisani et al., 2015;Vitale et al., 2012). It is unknown, however, if sensory disturbances are similarly observed in the processing of acoustic features embedded in the auditory signal. ...
Purpose
The purpose of the current study was to examine sensory and auditory memory limitations on intensity resolution in individuals with Parkinson's disease as compared to healthy older and younger adults.
Method
Nineteen individuals with Parkinson's disease, 10 healthy age- and hearing-matched adults, and 10 healthy young adults were studied. The listeners participated in 2 intensity discrimination tasks: a lower memory load 4IAX task (sensory limitations) and a higher memory load ABX task (auditory memory limitations). Intensity resolution was examined across groups and tasks using a bias-free measurement of signal detectability known as d ′ ( d -prime). Listeners also participated in a loudness scaling task where they were instructed to rate the loudness level of each signal intensity along the experimental continuum using a computerized 150-mm visual analog scale.
Results
Intensity discrimination sensitivity ( d ′) was significantly poorer in the 4IAX and ABX conditions for the individuals with Parkinson's disease, as compared to the older and younger controls. Furthermore, a significant age-related difference was identified for the loudness scaling condition. The younger controls rated most stimuli along the experimental continuum significantly louder as compared to the older controls and the individuals with Parkinson's disease.
Conclusions
The present discrimination data suggest sensory and auditory memory limitations may contribute to the intensity resolution issues associated with Parkinson's disease. Age-related differences in loudness scaling will be reviewed.
... The natural aging process together with neurodegenerative changes occurring in PD might hinder cochlear transduction mechanisms, thus anticipating presbycusis. α-Synuclein is present predominately in the efferent neuronal system within the inner ear, and it could affect susceptibility to noiseinduced hearing loss or presbycusis as explained by Vitale et al. [14]. Furthermore, Lai et al. [15] stated that as dopamine is a useful neurotransmitter that provides protection of the cochlea from noise exposure, its deficiency in PD can lead to damage to the cochlea and result in hearing loss. ...
... It is possible that the neurodegenerative process in PD affects the functionality of central auditory pathway, leading to a prolongation of wave latencies and peak intervals of auditory evoked potentials [14]. ...
Abstract Background Motor dysfunction in patients with Parkinson disease (PD) is just the tip of the iceberg. Auditory and vestibular dysfunction in patients with PD gained much attention owing to them being one of the nonmotor symptoms. Aim To explore abnormalities of pure tone audiometry (PTA), brainstem auditory evoked potentials (BAEPs), vestibular evoked myogenic potential (VEMP), and videonystagmography (VNG) in patients with PD and their correlation with motor and cognitive dysfunction. Patients and methods The study was conducted on 20 patients with PD and 15 controls. Selected patients were subjected to evaluation of motor symptoms using Unified Parkinson’s Disease Rating Scale (UPDRS) and cognitive function using Parkinson disease-Cognitive Rating Scale (PD-CRS). PTA, BAEPs, cervical VEMPs, and VNG were carried out for all patients and controls. Results Patients with PD show higher mean hearing thresholds at all PTA frequencies in both ears than controls. Analysis of BAEP demonstrated that patients with PD have significantly prolonged absolute latencies of wave III and wave V and interpeak latencies of I–III and I–V in both ears than controls. VEMP findings revealed that patients have significantly delayed P13 and N23 latencies and smaller P13–N23 amplitude in both ears than controls. VNG findings showed canal paresis in 60% of patients with PD and nystagmus in 60% of patients with PD. Correlative results revealed statistically significant correlations between VEMP parameters and UPDRS as well as PD-CRS, but there were no statistically significant correlations between PTA frequencies or BAEP latencies and UPDRS or PD-CRS. Conclusion Auditory and vestibular dysfunction is common in PD but cannot be totally correlated with the motor and cognitive symptoms.
... In Parkinson's disease, hearing impairment has been neglected as a non-motor symptom, partially because it is seen as a consequence of aging, despite recommendations to include it in the nonmotor symptom complex 1,2 ; with some studies suggesting it might even precede the onset of Parkinson's disease 3 . ...
... We found a high prevalence of hearing impairment for higher frequencies among Parkinson's disease patients, results that are congruent with previous studies 1,4 ; with severity increasing with frequency. Interestingly, we found lower motor and nonmotor scores among patients with hearing loss at higher frequencies, with lower scores on quality of life and self-efficacy measures, and no differences in cognition measures. ...
... Hearing dysfunction as a manifestation of PD has received little attention from researchers, probably because hearing impairment is not a common complaint of PD patients (Vitale et al., 2012). There is evidence for altered detection of auditory deviations in a number of tasks, frequency discrimination tasks, for example, have suggested that PD patients have more difficulty in discriminating small threshold frequency differences compared to healthy controls (De Groote et al., 2020). ...
Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.
... The participants reported no previous history of speech or language disorders. Occurrence of hearing impairment and use of hearing aids was explored through self-report but was not an exclusion criterion for this study, since hearing loss is common among the elderly [40] and often cooccurs with Parkinson's disease [41]. Overall disease severity was rated with the Hoehn and Yahr-scale [42], which has a range from stage 1 or very mild symptoms to stage 5 or severe symptoms with constant need of nursing care. ...
Introduction:
Assessment of intelligibility in dysarthria tends to rely on oral reading of sentences or words. However, self-generated utterances are closer to a clients' natural speech. This study investigated how transcription of utterances elicited by picture description can be used in the assessment of intelligibility in speakers with Parkinson's disease.
Methods:
Speech samples from eleven speakers with Parkinson's disease and six neurologically healthy persons were audio-recorded. Forty-two naive listeners completed transcriptions of self-generated sentences from a picture description task and orally read sentences from the Swedish Test of Intelligibility, as well as scaled ratings of narrative speech samples.
Results:
Intelligibility was higher in orally read than self-generated sentences and higher for content words than for the whole sentence in self-generated sentences for most of the speakers, although these within-group differences were not statistically significant at group level. Adding contextual leads for the listeners increased intelligibility in self-generated utterances significantly, but with individual variation. Although correlations between the intelligibility measures were at least moderate or strong, there was a considerable inter- and intra-speaker variability in intelligibility scores between tasks for the speakers with Parkinson's disease, indicating individual variation of factors that impact intelligibility. Intelligibility scores from neurologically healthy speakers were generally high across tasks with no significant differences between the conditions.
Discussion/conclusion:
Within-speaker variability support literature recommendations to use multiple methods and tasks when assessing intelligibility. The inclusion of transcription of self-generated utterances elicited by picture description to the intelligibility assessment has the potential to provide additional information to assessment methods based on oral reading of pre-scripted sentences, and to inform the planning of interventions.
... Natural aging processes and specific neurodegenerations in PD may adversely affect cochlear transduction mechanisms (Vitale et al., 2012). Therefore, investigating the function of cochlear mechanisms and assessment of hearing-related quality of life in individuals with PD is vital in following treatments. ...
Purpose
The effects of neurological diseases on the auditory system have been a notable issue for investigators because the auditory pathway is closely associated with neural systems. The purposes of this study are to evaluate the efferent auditory system function and hearing quality in Parkinson's disease (PD) and to compare the findings with age-matched individuals without PD to present a perspective on aging.
Method
The study included 35 individuals with PD (mean age of 48.50 ± 8.00 years) and 35 normal-hearing peers (mean age of 49 ± 10 years). The following tests were administered for all participants: the first section of the Speech, Spatial and Qualities of Hearing Scale; pure-tone audiometry, speech audiometry, tympanometry, and acoustic reflexes; and distortion product otoacoustic emissions (DPOAEs) and contralateral suppression of DPOAEs. SPSS Version 25 was used for statistical analyses, and values of p < .05 were considered statistically significant.
Results
There were no statistically significant differences in the pure-tone audiometry thresholds and DPOAE responses between the individuals with PD and their normal-hearing peers (p = .732). However, statistically significant differences were found between the groups in suppression levels of DPOAEs and hearing quality (p < .05). In addition, a statistically significant and positive correlation was found between the amount of suppression at some frequencies and the Speech, Spatial and Qualities of Hearing Scale scores.
Conclusions
This study indicates that medial olivocochlear efferent system function and the hearing quality of individuals with PD were affected adversely due to the results of PD pathophysiology on the hearing system. For optimal intervention and follow-up, tasks related to hearing quality in daily life can also be added to therapies for PD.
... These motor symptoms are reportedly correlated with the neural degeneration of the dopaminergic nigrostriatal pathway [2]. In addition to movement impairments, patients with Parkinson's disease may be affected by several nonmovement symptoms, such as sensorimotor deficits, which affect the voice and swallowing ability [3,4], and sensory impairments, which affect hearing function [5]. ...
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can damage dopaminergic neurons in the substantia nigra in many mammals with biochemical and cellular changes that are relatively similar to those observed in Parkinson's disease. Our study examined whether MPTP-treated echolocation bats can cause changes in bat echolocation system. By considering ultrasound spectrums, auditory brainstem-evoked potentials and flight trajectories of normal bats, we observed that the vocal, auditory, orientation and movement functions of MPTP-treated bats were significantly impaired, and they exhibited various symptoms resembling those in patients with Parkinson's disease. Our immunohistochemistry and western blot analyses further indicated that expression of vocal-related FOXP2 in the superior colliculus, auditory-related otoferlin in the inferior colliculus, dopamine synthesis-related aromatic l-amino acid decarboxylase in the substantia nigra and dopamine receptor in the striatum was significantly decreased. Furthermore, protein expression related to inflammation, oxidative stress and apoptosis in the substantia nigra was significantly increased in MPTP-treated bats. These results indicate that inflammation, oxidative stress and apoptosis may be instrumental in dopaminergic neurodegeneration in the substantia nigra. The vocal, auditory and orientation and movement dysfunctions of MPTP-treated bats are relatively consistent with symptoms of Parkinson's disease.
... Several genetic alterations to Otoferlin are found to be associated to the pathogenicity of hearing-related disorders (Varga et al., 2006), and PD patients are found prone to hearing loss or having difficulties in processing auditory inputs (Folmer et al., 2017). Therefore, Rab8b enrichment in EVs stimulated by high FGF2 levels (reported for the first time in our study) and its interactions supports a novel possibility of explaining molecular basis of non-motor symptoms like hearing loss in PD pathology (Vitale et al., 2012). Furthermore, hearing loss is associated to dementia as reported in Lin et al. (2011), and the relevance of the hippocampus in DLB is known (Liu et al., 2019). ...
Ras-associated binding (Rab) proteins are small GTPases that regulate the trafficking of membrane components during endocytosis and exocytosis including the release of extracellular vesicles (EVs). Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorder in the elderly population, where pathological proteins such as alpha-synuclein (α-Syn) are transmitted in EVs from one neuron to another neuron and ultimately across brain regions, thereby facilitating the spreading of pathology. We recently demonstrated fibroblast growth factor-2 (FGF2) to enhance the release of EVs and delineated the proteomic signature of FGF2-triggered EVs in cultured primary hippocampal neurons. Out of 235 significantly upregulated proteins, we found that FGF2 specifically enriched EVs for the two Rab family members Rab8b and Rab31. Consequently, we investigated the interactions of Rab8b and Rab31 using a network analysis approach in order to estimate the global influence of their enrichment in EVs. To achieve this, we have demarcated a protein-protein interaction network (PPiN) for these Rabs and identified the proteins associated with PD in various cellular components of the central nervous system (CNS), in different brain regions, and in the enteric nervous system (ENS). A total of 126 direct or indirect interactions were reported for two Rab candidates, out of which 114 are Rab8b interactions and 54 are Rab31 interactions, ultimately resulting in an individual interaction score (IS) of 90.48 and 42.86%, respectively. Conclusively, these results for the first time demonstrate the relevance of FGF2-induced Rab-enrichment in EVs and its potential to regulate PD pathophysiology.
... Thus, from these findings, individuals with PD would be expected to present higher frequency of complaints and auditory alterations as a consequence of dopaminergic deficit. However, previous clinical studies have revealed controversial findings regarding the perception of hearing difficulties and the audiometric profile in the disease (11,12) . ...
Purpose:
To evaluate the effect of levodopa on cochlear dynamics and on the medial olivocochlear efferent pathway of idiopathic Parkinson's disease (PD) individuals.
Methods:
Individuals with and without PD, followed at a University Hospital, were submitted to Distortion Product Otoacoustic Emissions (DPOAE) and DPOAE Inhibitory Effect (OAEIE) in the presence of contralateral noise. Correlation measures between DPOAE and OAEIE results with Hoehn&Yahr (H&Y) stage, daily dose of levodopa and PD diagnosis period were established. Furthermore, electroacoustic measures were compared between individuals without and those with PD, stratified by dose of levodopa daily administered.
Results:
Weak negative correlation between DPOAE amplitude and daily dose of levodopa was found, as well positive correlations between EIEOA with daily dose of levodopa and time of PD diagnosis, respectively. Higher DPOAE amplitude was found in individuals with PD using daily doses of levodopa ≤ 600 milligrams when compared to individuals without PD and those with PD using higher doses. EIEOA was lower in individuals using doses ≤ 600 milligrams, when compared to the other groups.
Conclusion:
Daily doses of levodopa up to 600 mg / day increase the cochlear mechanical-transducer responses in 2 and 3 kHz frequencies, while the action of olivocochlear efferent systems is reduced in this region.
... One study linked peripheral hearing impairment to general disability (i.e. not specifically cognitive dysfunction) in patients with Parkinson's disease (Vitale et al., 2012), but to my knowledge, no studies have systematically explored peripheral hearing alongside central auditory processing in PPA. ...
The primary progressive aphasias (PPA) are a diverse group of neurodegenerative disorders that selectively target brain networks mediating language. The pathophysiology of PPA remains poorly understood, but emerging evidence suggests that deficits in auditory processing accompany and may precede language symptoms in these patients. In four studies, I have probed the pathophysiology of auditory signal decoding in patient cohorts representing all major PPA syndromes – nonfluent variant PPA (nfvPPA), semantic variant PPA (svPPA), and logopenic variant PPA (lvPPA) – in relation to healthy age-matched controls. In my first experiment, I presented sequences of spoken syllables manipulated for temporal regularity, spectrotemporal structure and entropy. I used voxel-based morphometry to define critical brain substrates for the processing of these attributes, identifying correlates of behavioural performance within a cortico-subcortical network extending beyond canonical language areas. In my second experiment, I used activation functional magnetic resonance imaging (fMRI) with the same stimuli. I identified network signatures of particular signal attributes: nfvPPA was associated with reduced activity in anterior cingulate for processing temporal irregularity; lvPPA with reduced activation of posterior superior temporal cortex for processing spectrotemporal structure; and svPPA with reduced activation of caudate and anterior cingulate for processing signal entropy. In my third experiment, I manipulated the auditory feedback via which participants heard their own voices during speech production. Healthy control participants spoke significantly less fluently under delayed auditory feedback, but patients with nfvPPA and lvPPA were affected significantly less. In my final experiment, I probed residual capacity for dynamic auditory signal processing and perceptual learning in PPA, using sinewave speech. Patients with nfvPPA and lvPPA showed severely attenuated learning to the degraded stimuli, while patients with svPPA showed intact early perceptual processing, but deficient integration of semantic knowledge. Together, these experiments represent the most concerted and comprehensive attempt to date to define the pathophysiology of auditory signal decoding in PPA.
... is finding partially disagrees with evidence by Vitale and colleagues [24,25], instead demonstrating the occurrence of neurosensory hearing impairment in PD patients. e exclusion, in our study, of subjects with hearing thresholds over 50 dBHL even at a single frequency and additionally the smaller sample size and the different clinical-demographic features of the cohorts may account for this discrepancy. ...
Introduction:
Pisa syndrome (PS) is a postural complication of Parkinson's disease (PD). Yet, its pathophysiology remains unclear, although a multifactorial component is probable. Cervical vestibular evoked myogenic potentials (cVEMPs) explore vestibulospinal pathway, but they have not been measured yet in PD patients with PS (PDPS) to assess a potential vestibular impairment.
Materials and methods:
We enrolled 15 PD patients, 15 PDPS patients, and 30 healthy controls (HCs). They underwent neurological examination and were examined with Unified Parkinson's Disease Rating Scale II-III (UPDRSII-III), audiovestibular workup, and cVEMP recordings. Data were analysed with Chi-square, one-way ANOVA, multinomial regression, nonparametric, and Spearman's tests.
Results:
cVEMPs were significantly impaired in both PD and PDPS compared with HCs. PDPS exhibited more severe cVEMP abnormalities with prevalent bilateral loss of potentials, compared with the PD group, in which a prevalent unilateral loss was instead observed. No clinical-neurophysiological correlations emerged.
Conclusions:
Differently from HC, cVEMPs are altered in PD. Severity of cVEMPs alterations increases from PD without PS to PDPS, suggesting an involvement of vestibulospinal pathway in the pathophysiology of PS. Our results provide evidence for a significant impairment of cVEMPs in PDPS patients and encourage further studies to test validity of cVEMPs as diagnostic and prognostic biomarkers of PD progression.
... This, in turn, would induce oxidative damage and loss of hair cells, supporting cells, ganglion cells, and fibrocytes in the stria vascularis (Bielefeld et al., 2010;Huang and Tang, 2010;Fetoni et al., 2011;Yamasoba et al., 2013;Fujimoto and Yamasoba, 2014;Alvarado et al., 2015b;Melgar-Rojas et al., 2015b). Excess free radical formation seems to be part of a common pathogenic pathway ( Alvarado et al., 2015b;Tavanai and Mohammadkhani, 2017) which is involved in other forms of hearing loss such as NIHL and DIHL ( Henderson et al., 2006;Le Prell et al., 2007a,b;Bielefeld et al., 2010;Fetoni et al., 2011) as weel as in many neurodegenerative pathologies (Ames et al., 1993;Lin and Beal, 2006;Gardiner et al., 2009) that present high incidence of hearing loss (Lin Y.S. et al., 2011;Vitale et al., 2012;Hung et al., 2015;Hardy et al., 2016;Folmer et al., 2017;Profant et al., 2017;Zheng et al., 2017). Age-related degeneration or atrophy of the stria vascularis, including the accompanying microvasculature, affects the EP and therefore, the amplification of acoustic signals, leading to an increase in auditory thresholds ( Mills and Schmiedt, 2004;Bielefeld et al., 2010;Huang and Tang, 2010;Schmiedt, 2010;Fetoni et al., 2011;Shi, 2011;Lee, 2013;Melgar-Rojas et al., 2015b). ...
The increasing rate of age-related hearing loss (ARHL), with its subsequent reduction in quality of life and increase in health care costs, requires new therapeutic strategies to reduce and delay its impact. The goal of this study was to determine if ARHL could be reduced in a rat model by administering a combination of antioxidant vitamins A, C, and E acting as free radical scavengers along with Mg++, a known powerful cochlear vasodilator (ACEMg). Toward this goal, young adult, 3 month-old Wistar rats were divided into two groups: one was fed with a diet composed of regular chow (“normal diet,” ND); the other received a diet based on chow enriched in ACEMg (“enhanced diet,” ED). The ED feeding began 10 days before the noise stimulation. Auditory brainstem recordings (ABR) were performed at 0.5, 1, 2, 4, 8, 16, and 32 kHz at 3, 6–8, and 12–14 months of age. No differences were observed at 3 months of age, in both ND and ED animals. At 6–8 and 12–14 months of age there were significant increases in auditory thresholds and a reduction in the wave amplitudes at all frequencies tested, compatible with progressive development of ARHL. However, at 6–8 months threshold shifts in ED rats were significantly lower in low and medium frequencies, and wave amplitudes were significantly larger at all frequencies when compared to ND rats. In the oldest animals, differences in the threshold shift persisted, as well as in the amplitude of the wave II, suggesting a protective effect of ACEMg on auditory function during aging. These findings indicate that oral ACEMg may provide an effective adjuvant therapeutic intervention for the treatment of ARHL, delaying the progression of hearing impairment associated with age.
... We found a high prevalence of hearing impairment for higher frequencies among Parkinson's disease patients, results that are congruent with previous studies 1,4 ; with severity increasing with frequency. Interestingly, we found lower motor and nonmotor scores among patients with hearing loss at higher frequencies, with lower scores on quality of life and self-efficacy measures, and no differences in cognition measures. ...
Objective. To evaluate the presence of sensorineural hearing loss in a mexican population of Parkinson’s disease (PD) patients, and describe the clinical characteristics of such population.
Background. Despite being a common consequence of aging, hearing loss has not been thoroughly studied in Parkinson’s disease patients[1], and could represent part of the non-motor symptom conundrum[2].
Methods. We designed a transversal study to evaluate the presence of sensorineural hearing loss in a Mexican population of Parkinson’s disease patients. We recruited 16 patients whose baseline characteristics are described in table 1. Bilateral pure tone audiometry, through frequencies ranging from 125kHz to 8000kHz was used to evaluate hearing loss, and was defined as present when above 21 dB in any given frequency. We evaluated PD severity by motor subtype, MDS-UPDRS motor score, and non-motor symptom scale (NMSS).
Results. Prevalence of sensorineural hearing loss was 87%; with prevalence increasing with age and higher frequencies. Laterality and symmetry of hearing loss are shown in figure 1, and severity is shown in Figure 2. Tremor-dominant was the most common subtype across all frequencies, and no difference was seen in years with Parkinson’s Disease. MDS-UPDRS and NMSS Scores showed a tendency to decrease in patients with hearing loss at higher frequencies, as shown in table 2.
Conclusion. Hearing loss is common in PD. As expected, hearing loss was more prevalent (and at higher frequencies) as age increased; interestingly we found lower motor and non-motor scores among patients with hearing loss at higher frequencies. Further and larger studies are required to clarify the relationship between these two entities.
References
1. Vitale C, Marcelli V, Allocca R, Santangelo G, Riccardi P, Erro R, et al. Hearing impairment in Parkinson’s disease: Expanding the nonmotor phenotype. Mov Disord. 2012;27(12):1530–5.
2. Lai SW, Liao KF, Lin CL, Lin CC, Sung FC. Hearing loss may be a non-motor feature of Parkinson’s disease in older people in Taiwan. Eur J Neurol. 2014;21(5):752–7.
... Para tal, a classificação da força de associação estatística foi considerada de 0 a < 0,1 (ausência de associação); 0,1 a < 0,3 (fraca associação); 0,3 a < 0,5 (moderada associação); e 0,5 a 1,0 (forte associação). Foi calculado ainda o índice h de Cohen 26 , para verificar se houve diferença estatística entre os grupos com e sem percepção do handicap auditivo nos testes de PA (C). Para fins desta análise, foi considerado sem efeito h < 0,2; efeito fraco h entre 0,2 -0,49; efeito moderado h entre 0,5 -0,79 e; efeito forte h>= 0,8. ...
Purpose:
to investigate the relationship between the perception of self-reported hearing impairment and the handicap with peripheral and central hearing alterations, in individuals with Parkinson's disease.
Methods:
individuals with Parkinson's disease were seen and evaluated at a reference outpatient clinic for the treatment of movement disorders, between April and August 2015. All of them underwent basic audiological evaluation and hearing processing tests. The hearing handicap assessment was performed using the Hearing Handicap Inventory for the Elderly. As for the analysis of the relationship between hearing handicap perception and audiological, clinical and demographic variables, individuals were considered with or without perception, according to their score.
Results:
thirty-three individuals, mostly males, with a mean age of 63.7 years, took part in the study. There was a high frequency (n = 31) of peripheral or central hearing alterations in the study population. However, only 14 reported some difficulty in hearing, eight not presenting hearing handicap perception, two having mild-moderate perception and four showing a significant perception.
Conclusion:
the perceptions of hearing difficulties and the handicap are not related to audiological alterations in individuals presented with Parkinson's disease.
... [17] Brainstem Auditory Potentials and Parkinson's disease: Studies of Brainstem Auditory Potentials in Parkinson's disease auditory function were variable. Carmine Vitale et al [18] found normal latencies but M.J. Gawel et al. [19] , Süleyman Yýlmaz et al. [20] , Fradis et al. [21] and Daniel et al [22] have reported prolonged Brainstem Auditory Response whereas Prasher et al [23] found no significant difference between PD with healthy controls. The aim of this study was to evaluate the Brainstem Auditory Evoked Response in patients with Parkinson's disease. ...
... This means that it cannot be inferred that interactions with few occurrences of repair are always functional, at least not if the transmission of information is more important than the social interaction in the conversation. Impaired hearing is common in older age [50], and particular in relation to PD [51]. Impaired hearing may of course have impacts on the need for repair in conversational interaction and was an exclusion criterion for both the PwPDs and the CPs in this study. ...
It is known that Parkinson's disease is often accompanied by a motor speech disorder, which results in impaired communication. However, people with Parkinson's disease may also have impaired word retrieval (anomia) and other communicative problems, which have a negative impact on their ability to participate in conversations with family as well as healthcare staff. The aim of the present study was to explore effects of impaired speech and language on communication and how this is managed by people with Parkinson's disease and their spouses. Using a qualitative method based on Conversation Analysis, in-depth analyses were performed on natural conversational interaction in five dyads including elderly men who were at different stages of Parkinson's disease. The findings showed that the motor speech disorder in combination with word retrieval difficulties and adaptations, such as using communication strategies, may result in atypical utterances that are difficult for communication partners to understand. The coexistence of several communication problems compounds the difficulties faced in conversations and individuals with Parkinson's disease are often dependent on cooperation with their communication partner to make themselves understood.
... Interestingly, a loss of hearing was recently described as a non-motor symptom in Parkinson's disease (Vitale et al., 2012;Lai et al., 2014). In detail, auditory impairment in parkinsonian patients, measured through oto-acoustic emission recording and pure-tone audiometry, are improved by L-DOPA treatment. ...
Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum) of Wistar rats. Rats were exposed to loud noise (100 dBA) for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay. In parallel studies, brain monoamine levels and morphology of nigrostriatal pathways, hippocampus and cerebellum were analyzed at different time intervals (24 h and 7 days) after noise exposure. Loud noise produced a sudden increase in DNA damage in all the brain areas under investigation. Monoamine levels detected at 7 days following exposure were differently affected depending on the specific brain area. Namely, striatal but not hippocampal dopamine (DA) significantly decreased, whereas hippocampal and cerebellar noradrenaline (NA) was significantly reduced. This is in line with pathological findings within striatum and hippocampus consisting of a decrease in striatal tyrosine hydroxylase (TH) combined with increased Bax and glial fibrillary acidic protein (GFAP). Loud noise exposure lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune-histochemical alterations within specific brain areas of the rat. These alterations may suggest an anatomical and functional link to explain the neurobiology of diseases which prevail in human subjects exposed to environmental noise. © 2017 Frenzilli, Ryskalin, Ferrucci, Cantafora, Chelazzi, Giorgi, Lenzi, Scarcelli, Frati, Biagioni, Gambardella, Falleni and Fornai.
Objective
To investigate the implications of Parkinson’s disease (PD) in the peripheral auditory system, a systematic survey of the scientific literature was conducted.
Design
Systematic review.
Study sample
An electronic search of the non-gray literature in the last decade was conducted using the digital databases MEDLINE® (PubMed interface), LILACS® (Virtual Health Library), Web of Science® (CAPES publications portal), and SciELO®. Studies addressing peripheral auditory function as part of the range of nonmotor PD symptoms were selected for analysis.
Results
Pure tone audiometry data suggested that sensorineural hearing loss was more severe in the PD population than in the control groups. The effects of PD on cochlear function were evidenced by a decrease in the levels of otoacoustic emissions.
Conclusions
Sensorineural hearing loss and cochlear impairment are more severe in the PD population than in the control groups. Additional studies are recommended to further understand the characteristics of the peripheral auditory system in PD patients, which constitutes an emerging subject in the scientific literature.
Extracellular vesicles (EVs) are small lipid bilayer particles ubiquitously released by almost every cell type. A specific and selective constituents of EVs loaded with variety of proteins, lipids, small noncoding RNAs, and long non-coding RNAs are reflective of cellular events, type, and physiologic/pathophysiologic status of the cell of origin. Moreover, these molecular contents carry information from the cell of origin to recipient cells, modulating intercellular communication. Recent studies demonstrated that EVs not only play a neuroprotective role by mediating the removal of toxic proteins, but also emerge as an important player in various neurodegenerative disease onset and progression through facilitating of misfolded proteins propagation. For this reason, neurodegenerative disease-associated differences in EV proteome relative to normal EVs can be used to fulfil diagnostic, prognostic, and therapeutic purposes. Nonetheless, characterizing EV proteome obtained from biological samples (brain tissue and body fluids, including urea, blood, saliva, and CSF) is a challenging task. Herein, we review the status of EV proteome profiling and the updated discovery of potential biomarkers for the diagnosis of neurodegenerative disease with an emphasis on the integration of high-throughput advanced mass spectrometry (MS) technologies for both qualitative and quantitative analysis of EVs in different clinical tissue/body fluid samples in past five years.
Several causative factors are associated with hearing loss (HL) and brain disorders. However, there are many unidentified disease modifiers in these conditions. Our study summarised the most common brain disorders associated with HL and highlighted mechanisms of pathologies. We searched the literature for published articles on HL and brain disorders. Alzheimer’s disease/dementia, Parkinson’s disease, cognitive impairment, autism spectrum disorder, ataxia, epilepsy, stroke, and hypoxic-ischaemic encephalopathy majorly co-interact with HL. The estimated incidence rate was 113 per 10,000 person-years. Genetic, epigenetic, early life/neonatal stress, hypoxia, inflammation, nitric oxide infiltration, endoplasmic reticulum stress, and excess glutamate were the distinguished modifiers identified. Various mechanisms like adhesion molecules, transport proteins, hair cell apoptosis, and neurodegeneration have been implicated in these conditions and are serving as potential targets for therapies. To improve the quality of life of patients, these understandings will improve clinical diagnoses and management of HL and brain disorders.
Purpose
A retrospective analysis was conducted to explore how tinnitus, one or more neurologic conditions, unaided speech intelligibility index, and other comorbidities impact the average number of hours hearing aids are worn each day by U.S. Military Veterans.
Method
Medical records and a hearing aid database were queried to obtain information regarding active medical problems and average daily hearing aid wear time. Multiple linear regression was used to explore these relationships for 215 male Veterans whose records were available from 2009 to 2020. To be analyzed, Veterans must have possessed their hearing aid(s) for at least 3 consecutive months.
Results
An active problem of subjective tinnitus was associated with increased hearing aid wear time (positive association) and one or more active neurologic conditions were associated with decreased hearing aid wear time (negative association). A high unaided speech intelligibility index (greater access to speech sounds without hearing aids) was also associated with decreased hearing aid wear time (negative association).
Conclusions
There are many complex audiologic and medical concerns that may affect hearing aid wear time in U.S. Military Veterans. Therefore, the information from this study should be expanded on prospectively by further exploring these associations, and their severity, on hearing aid wear time. The information from this and future studies may lead to clinical recommendations with the goal of increasing daily hearing aid use in this and other populations.
The result of the actions of the telomere-subtelomere-telomerase system, in our species and in many similar species, is the atrophic syndrome, already briefly outlined in the preceding Chapter 5 – Subtelomere-Telomere aging theory, which manifests itself progressively and in relation to age in all tissues and organs. The characteristics of the atrophic syndrome are now discussed with more details.
Dose-limiting toxicities for cisplatin administration, including ototoxicity and nephrotoxicity, impact the clinical utility of this effective chemotherapy agent and lead to lifelong complications, particularly in pediatric cancer survivors. Using a two-pronged drug screen employing the zebrafish lateral line as an in vivo readout for ototoxicity and kidney cell-based nephrotoxicity assay, we screened 1280 compounds and identified 22 that were both oto- and nephroprotective. Of these, dopamine and L-mimosine, a plant-based amino acid active in the dopamine pathway, were further investigated. Dopamine and L-mimosine protected the hair cells in the zebrafish otic vesicle from cisplatin-induced damage and preserved zebrafish larval glomerular filtration. Importantly, these compounds did not abrogate the cytotoxic effects of cisplatin on human cancer cells. This study provides insights into the mechanisms underlying cisplatin-induced oto- and nephrotoxicity and compelling preclinical evidence for the potential utility of dopamine and L-mimosine in the safer administration of cisplatin.
This study aimed to assess hearing loss and speech recognition impairment in patients with Parkinson disease (PD) based on Mandarin through pure-tone audiometry and speech audiometry. In total, 32 PD patients and 32 age-matched normal controls were enrolled for pure-tone audiometry and speech audiometry using a GSI arrow audiometer together with the BOSCH Chinese speech audiometry system. The results of pure-tone audiometry showed that PD patients exhibited more severe low-, medium-, or high-frequency hearing loss than normal controls, especially at higher frequencies, and there were significant differences in gender. In addition, the results of speech audiometry showed that the speech recognition threshold of PD patients was significantly higher than that of normal controls. Furthermore, at any of the 3 hearing levels of 70, 50, and 30 dB HL, the recognition rates of initials, finals, and tones were successively decreased in PD patients, especially initials. PD patients exhibited significant hearing loss and speech recognition impairment. The initial recognition was more dependent on the hearing levels.
Purpose
Alterations in primary auditory functioning have been reported in patients with Parkinson's disease (PD). Despite the current findings, the pathophysiological mechanisms underlying these alterations remain unclear, and the effect of dopaminergic medication on auditory functioning in PD has been explored insufficiently. Therefore, this study aimed to systematically investigate primary auditory functioning in patients with PD by using both subjective and objective audiological measurements.
Method
In this case–control study, 25 patients with PD and 25 age-, gender-, and education-matched healthy controls underwent an audiological test battery consisting of tonal audiometry, short increment sensitivity index, otoacoustic emissions (OAEs), and speech audiometry. Patients with PD were tested in the on- and off-medication states.
Results
Increased OAE amplitudes were found when patients with PD were tested without dopaminergic medication. In addition, speech audiometry in silence and multitalker babble noise demonstrated higher phoneme scores for patients with PD in the off-medication condition. The results showed no differences in auditory functioning between patients with PD in the on-medication condition and healthy controls. No effect of disease stage or motor score was evident.
Conclusions
This study provides evidence for a top-down involvement in auditory processing in PD at both central and peripheral levels. Most important, the increase in OAE amplitude in the off-medication condition in PD is hypothesized to be linked to a dysfunction of the olivocochlear efferent system, which is known to have an inhibitory effect on outer hair cell functioning. Future studies may clarify whether OAEs may facilitate an early diagnosis of PD.
Objective:
Recent reports of hearing impairment in Parkinson's disease (PD) have suggested that auditory dysfunction could be a non-motor manifestation of PD. These reports were based on observations of elderly patients for whom presbycusis may, to some extent, have contributed to hearing dysfunction. Therefore, we aimed to explore the auditory functions in younger patients with PD.
Methods:
We conducted a case-control study in a relatively younger (< 55 years of age at study time) population of PD patients and healthy volunteers to test whether auditory dysfunction is a significant non-motor dysfunction in PD. Pure tone audiometry (PTA) and brainstem evoked response audiometry (BERA) were performed in all participants.
Results:
None of the patients or controls reported hearing deficits. Fifty-one patients with PD and 50 healthy volunteers who were age- and gender-matched to the patients participated. PTA-detected hearing impairment was found in 64.7% of patients and 28% of controls (p < 0.001) for both low-mid and/or high frequencies. Hearing impairment was more frequent in the younger subgroups of patients than age-matched controls, while the frequency of hearing impairment was similar in older groups of subjects. BERA was not different between patients and controls.
Conclusion:
Asymptomatic auditory dysfunction is a common non-motor manifestation of early-onset PD and more frequent in younger patients, indicating that it may be independent of aging. The mechanism underlying this dysfunction appears to be peripheral, although a central dysfunction cannot be ruled out based on the findings of this study.
Neurodegeneratieve aandoeningen worden gekenmerkt door een prodromale fase waarin het pathologische proces reeds is ingezet, maar de dominante klinische symptomen zich nog niet hebben gemanifesteerd. Het identificeren van diagnostische biomerkers voor de vroegdetectie van deze aandoeningen biedt de mogelijkheid tot het plannen van vroegtijdige interventies en het afremmen van het pathologisch proces en geassocieerde klinische symptomen. Een biomerker is idealiter objectief, non-invasief en voldoende beschikbaar. Elektro-encefalografie (EEG) is een techniek die voldoet aan deze criteria en is mogelijk in staat subtiele veranderingen in de prodromale fase te detecteren. Ook de ziekte van Parkinson (PD) en Primair Progressieve Afasie (PPA) worden doorgaans pas laattijdig gediagnosticeerd op basis van de dominante motorische en talige symptomen, respectievelijk. In wat volgt geven wij een systematisch overzicht van potentiële elektrofysiologische biomerkers in het logopedische en audiologische onderzoeksdomein. Talige en auditieve elektrofysiologische biomerkers lijken veelbelovend voor de vroegdetectie van respectievelijk PPA en PD.
Background
Increased depression, hearing loss, dementia, alcoholism, and mortality in essential tremor patients remain unexplained. We investigated whether conditions associated with tremor are linked to chronic stress.
Methods
The FY2013 Veterans Affairs database was queried for 38 selected dual diagnosis combinations in 5,854,223 veterans aged 21–95 years.
Results
Post-traumatic stress disorder, anxiety, and depression were the most common psychiatric diagnoses in tremor patients, with the odds ratio exceeding 2 in all 15-year cohorts. Depending on age, patients with essential tremor were more likely than those without to have obsessive–compulsive disorder, bipolar illness, schizophrenia, use tobacco and abuse alcohol, have hypertension, obesity, hyperlipidemia, diabetes, vitamin D deficiency, coronary and cerebrovascular diseases, congestive heart failure, stroke, asthma, hypothyroidism, irritable bowel syndrome, renal insufficiency, alcoholic liver disease, hearing loss, glaucoma, macular degeneration, migraine, epilepsy, idiopathic polyneuropathy, history of head trauma, and ‘Alzheimer’s dementia. In contrast, lung and colorectal cancer, amyotrophic lateral sclerosis, psychostimulant abuse, and rheumatoid arthritis were not more common.
Discussion
Post-traumatic stress disorder, anxiety, and depression, strongly associated with essential tremor, are known risk factors for poor health habits, tobacco use and alcohol abuse; collectively these are risk factors for vascular disease, with further negative health consequences for multiple organ systems. As essential tremor is associated with all these conditions, we propose that chronic stress is not only responsible for the conditions associated with tremor but in some cases itself directly and indirectly induces essential tremor, so that tremor and poor health share a common cause.
Anterograde tracing methods were used to examine the topographic organization and interrelationship of projections to the neostriatum arising from various areas of association cortex. In contrast to the currently accepted topographic schema, all cortical areas examined project to longitudinal territories that occupy restricted medial-lateral domains of the neostriatum. The posterior parietal and superior arcuate cortices project to dorsolateral portions of the neostriatum; the dorsolateral and dorsomedial frontal cortices project centrally; and the orbitofrontal, anterior cingulate, and superior temporal projections are distributed to ventromedial regions of the caudate nucleus and putamen. In coronal section, cortical terminal fields form a diagonal strip, extending from the dorsal, ventricular border of the caudate nucleus, through the fiber bundles of the internal capsule, to the ventral margin of the putamen. Double labeling studies, in which two cortical areas were injected in the same animal, indicated that convergence of input within neostriatal domains is not governed by reciprocity of corticocortical connectivity. Thus, the interrelationship of projections arising from connectionally linked cortical areas ranged from nearly complete segregation of terminal fields (e.g., from dorsolateral prefrontal and orbital cortices) to extensive overlap of terminal domains (e.g., from frontal and temporal cortices). In the latter case, detailed analysis revealed that frontal and temporal terminals actually were interdigitated rather than intermixed within the zone of overlap. The present findings suggest a new conceptualization of corticostriatal topography in the primate which emphasizes the longitudinal arrangement of cortical terminal domains. Additionally, these findings provide a map for functional parcellation of the neostriatum on the basis of its cortical innervation which may prove useful to understanding normal striatal function, as well as the symptomatology associated with neostriatal injury and disease.
To determine whether hearing loss is associated with incident all-cause dementia and Alzheimer disease (AD).
Prospective study of 639 individuals who underwent audiometric testing and were dementia free in 1990 to 1994. Hearing loss was defined by a pure-tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear (normal, <25 dB [n = 455]; mild loss, 25-40 dB [n = 125]; moderate loss, 41-70 dB [n = 53]; and severe loss, >70 dB [n = 6]). Diagnosis of incident dementia was made by consensus diagnostic conference. Cox proportional hazards models were used to model time to incident dementia according to severity of hearing loss and were adjusted for age, sex, race, education, diabetes mellitus, smoking, and hypertension.
Baltimore Longitudinal Study of Aging.
Six hundred thirty-nine individuals aged 36 to 90 years.
Incident cases of all-cause dementia and AD until May 31, 2008.
During a median follow-up of 11.9 years, 58 cases of incident all-cause dementia were diagnosed, of which 37 cases were AD. The risk of incident all-cause dementia increased log linearly with the severity of baseline hearing loss (1.27 per 10-dB loss; 95% confidence interval, 1.06-1.50). Compared with normal hearing, the hazard ratio (95% confidence interval) for incident all-cause dementia was 1.89 (1.00-3.58) for mild hearing loss, 3.00 (1.43-6.30) for moderate hearing loss, and 4.94 (1.09-22.40) for severe hearing loss. The risk of incident AD also increased with baseline hearing loss (1.20 per 10 dB of hearing loss) but with a wider confidence interval (0.94-1.53).
Hearing loss is independently associated with incident all-cause dementia. Whether hearing loss is a marker for early-stage dementia or is actually a modifiable risk factor for dementia deserves further study.
We aimed to determine the value of the paired-pulse inhibition (PPI) in the auditory cortex in patients with Parkinson's disease (PD) and analyze its dependence on clinical characteristics of the patients. The central (Cz) auditory evoked potentials were recorded in 58 patients with PD and 22 age-matched healthy subjects. PPI of the N1/P2 component was significantly (P < .001) reduced for interstimulus intervals 500, 700, and 900 ms in patients with PD compared to control subjects. The value of PPI correlated negatively with the age of the PD patients (P < .05), age of disease onset (P < .05), body bradykinesia score (P < .01), and positively with the Mini Mental State Examination (MMSE) cognitive score (P < .01). Negative correlation between value of PPI and the age of the healthy subjects (P < .05) was also observed. Thus, results show that cortical inhibitory processes are deficient in PD patients and that the brain's ability to carry out the postexcitatory inhibition is age-dependent.
Synucleins are widely expressed synaptic proteins within the central nervous system that have been implicated in such neurodegenerative disorders as Parkinson's disease. In this study, an initial characterization of all three synucleins, alpha-, beta-, and gamma-synuclein, within the cochlea was undertaken. Reverse transcriptase-polymerase chain reaction (PCR) demonstrated all three synuclein mRNA species within microdissected cochlear tissue. Quantitative PCR suggests that beta-synuclein is the most abundantly expressed form, followed by gamma- and then alpha-synuclein. Western blot analysis similarly demonstrates all three synuclein proteins within microdissected cochlear tissue. Immunofluorescence localizes the three synucleins predominantly to the efferent neuronal system at the efferent outer hair cell synapse, with some additional localization within the efferent tunnel-crossing fibers (alpha- and gamma-synuclein), spiral ganglion (beta-synuclein), inner spiral bundle (gamma-synuclein), and stria vascularis (alpha- > beta-synuclein). Developmentally, gamma-synuclein can be seen in the region of the outer hair cells by E19, while alpha- and beta-synuclein do not clearly appear there until approximately P10. Additional studies in a null-mutant gamma-synuclein mouse show no histological changes in the organ of Corti with normal hair cell and spiral ganglion cell counts, and normal ABR and DPOAE thresholds in wild-type vs mutant littermates. Together, these results localize synucleins to the efferent cholinergic neuronal auditory system, pointing to a role in normal auditory function, and raising the potential implications for their role in auditory neurodegenerative disorders. However, gamma-synuclein alone is not required for the development and maintenance of normal hearing through P21. Whether overlapping roles of the other synucleins help compensate for the loss of gamma-synuclein remains to be determined.
Brain stem potentials from three groups of patients, namely those with pure progressive autonomic failure, Parkinson's disease and multisystem atrophy with progressive autonomic failure (Shy-Drager syndrome) were compared with each other and a group of normal subjects. In virtually all the patients with multisystem atrophy with progressive autonomic failure the brain stem potentials were abnormal in contrast to normal findings with Parkinson's disease. The closely associated group of patients with progressive autonomic failure alone also revealed no abnormalities of the BAEP. This separation of the two groups, Parkinson's disease and progressive autonomic failure from multisystem atrophy with progressive autonomic failure is important clinically as multiple system atrophy of the Shy-Drager type has extra-pyramidal features closely resembling Parkinsonism or a late onset cerebellar degeneration. From the abnormalities of the brain stem response in multisystem atrophy with progressive autonomic failure, it is clear that some disruption of the auditory pathway occurs in the ponto-medullary region as in nearly all patients there is a significant delay or reduction in the amplitude of components of the response generated beyond this region. The most likely area involved is the superior olivary complex.
Corticostriatal connections of auditory areas within the supratemporal plane and in rostral and caudal portions of the superior temporal gyrus were studied by the autoradiographic anterograde tracing technique. The results show that the primary auditory cortex has limited projections to the caudoventral putamen and to the tail of the caudate nucleus. In contrast, the second auditory area within the circular sulcus has connections to the rostral and the caudal putamen and to the body of the caudate nucleus and the tail. The association areas of the superior temporal gyrus collectively have widespread corticostriatal projections characterized by differential topographic distributions. The rostral part of the gyrus projects to ventral portions of the head of the caudate nucleus and of the body and to the tail. In addition, there are connections to rostroventral and caudoventral portions of the putamen. The mid-portion of the gyrus projects to similar striatal regions, but the connections to the head of the caudate nucleus are less extensive. Compared with the rostral and middle parts of the superior temporal gyrus, the caudal portion has little connectivity to the tail of the caudate nucleus. It projects more dorsally within the head and the body and also more dorsally within the caudal putamen. These differential patterns of corticostriatal connectivity are consistent with functional specialization at the cortical level.
Summary There is conjoining experimental and clinical evidence supporting a fundamental role of the basal ganglia as a sensory analyser engaged in central somatosensory control. This study was aimed at investigating the functional anatomy of sensory processing in two clinical conditions characterized by basal ganglia dysfunction, i.e. Parkinson's and Huntington's disease. Based on previously recorded data of somatosensory evoked potentials, we expected deficient sensory-evoked activation in cortical areas that receive modulatory somatosensory input via the basal ganglia. Eight Parkinson's disease patients, eight Huntington's disease patients and eight healthy controls underwent repetitive H215O-PET activation scans during two experimental conditions in random order: (i) continuous unilateral high-frequency vibratory stimulation applied to the immobilized metacarpal joint of the index finger and (ii) rest (no vibratory stimulus). In the control cohort, the activation pattern was lateralized to the side opposite to stimulus presentation, including cortical (primary sensory cortex (S1); secondary sensory cortex (S2)) and subcortical (globus pallidus, ventrolateral thalamus) regional cerebral blood flow (rCBF) increases ( P < 0.001). Between-group comparisons (P < 0.01) of vibration-induced rCBF changes
Non-motor symptoms (NMS) are common in Parkinson's disease (PD), affecting up to 90% of patients during their illness, and include neuropsychiatric complications, autonomic disorders, sleep disturbances and sensory symptoms. Although NMS correlate strongly with advancing disease, they may precede the onset of motor symptoms by a number of years. It is increasingly recognised that NMS result in a significant burden for people with PD and affect quality of life (QoL) to a greater extent than motor features. However, NMS often remain undiagnosed and untreated. Herein we review the impact of common NMS on QoL for patients with PD.
Objectives:
To determine the prevalence and characteristics of hearing loss in patients undergoing examination because of a memory disorder, to determine whether currently used screening tools were adequate for use in this specific population, and to determine if patients with Alzheimer disease reliably report hearing problems.Design:
Case-control study.Patients:
A consecutive sample of 52 patients: 30 patients who met the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease (group 1) and 22 patients with other forms of cognitive impairment (group 2).Methods:
Patients underwent a hearing screening that included a case history, a visual inspection of the external ear canal and tympanic membrane, and pure tone audiometry. Patients and their caregivers completed a questionnaire intended to assess hearing impairment and perceived disability.Outcome Measures:
Pass or fail on pure tone audiometry and pass or fail on a hearing impairment questionnaire.Results:
Of the 52 patients, 49 had significant hearing loss. No difference was found in the failure rate between patients in groups 1 and 2. In group 1, a significant discrepancy was found between the patient's self-report and that of their caregivers, whereas in group 2, the self-report was reliable. The prevalence of hearing loss in this population greatly exceeds the prevalence in healthy aged controls.Conclusion:
The extraordinarily high prevalence of hearing loss in this selected population suggests that a hearing evaluation should be part of any assessment of cognitive function.
Many studies have documented the decline in auditory function with age. We broaden that data base in this the first of a series of reports emanating from the auditory testing of the Framingham cohort during biennial exam 18. The results of the auditory questionnaire, hearing sensitivity, acoustic compliance measures, and word recognition tests obtained from 1662 men and women in their 60th through 90th decades are presented. Pure-tone thresholds increased with age but the rate of change with age did not differ by gender even though men had poorer threshold sensitivity. Maximum word recognition ability declined with age more rapidly in men than in women and was poorer in men than in women at all ages. Acoustic compliance and middle ear pressure did not vary with gender or age. Acoustic reflex thresholds to a contralat-era1 stimulus at 1 kHz increased slightly with age, more in women than in men; ipsilateral acoustic reflex thresholds did not vary with age or gender. Hearing aids were being used in only 10% of subjects likely to benefit from amplification.
Our observations support the concept of bilateral cortical activation with monaural and binaural auditory stimulation. The observation that most of the significantly activated areas were the same with monaural or binaural stimulation suggests that the differences in auditory perception with binaural stimulation are not due to the involvement of significantly different processing centers but, more likely, to the type of information that reaches these centers for processing. The observation that the degree of stimulation was less intense in binaural than in monaural stimulation supports the concept that a richer binaural auditory stimulation compared with monaural stimulation does not mean summation of stimuli but integration and better processing of the information. For normal bilateral hearing subjects, a monaural stimulus is an uncommon event and may thus explain the more intense response. The repeatability of the results for monaural and binaural stimulation with pure tones in the same subjects confirms the consistency of the testing method.
(1) To determine which areas of the cerebral cortex and basal ganglia are activated by binaural stimulation with pure tones (left and right ear simultaneously) and what type of response occurs (e.g. excitatory or inhibitory) in these different areas. (2) To determine the degree of ipsilateral and/or contralateral cortical activation and/or inhibition. (3) To compare the data with our previous reports of monaural stimulation using the same technique and the same subjects. (4) To evaluate the consistency of our testing method.
Brain perfusion single photon emission computed tomography (SPECT) evaluation was conducted using auditory binaural stimulation with pure tones in six normal volunteers. Both ears were stimulated simultaneously. Tc99m HMPAO was injected while pure tones were delivered and the SPECT imaging was done 1 h later.
After delivering pure tones there was bilateral activation in Brodmann areas 7 (somatosensory association cortex), 9 and 10 (executive frontal areas), 17, 18, and 19 (associative visual cortex). There was also activation in temporal areas 21, 22 (auditory association areas), and parietal areas 39 and 40 (Wernicke). There was also marked activation in both thalami. These activated areas were the same as those in our previous reports with monaural stimulation in the same subjects. However, except for areas 17, 18, 23, 31, and 32 (which remained over 4 SD above the normal maximum), the degree of activation was less intense in binaural compared with monaural stimulation. Inhibition was also less intense in binaural stimulation.
In the course of Parkinson disease (PD), apart from motor symptoms, presence of mental disturbances such as dementia and depression is common. The aims of this study were to assess the auditory system involvement in patients with PD using electrophysiological and neuropsychological tests and to correlate the cognitive impairment and the auditory evoked potentials tests results. The auditory and cognitive functions were studied in 53 patients with idiopathic PD, mean age 65.8 +/- 9.1 years; mean disease duration 7.8 +/- 5.0 years; mean motor disability score 2.5 +/- 0.8 points in Hoehn-Yahr scale compared with a control group matched for age and sex. In patients and controls, cognitive functions were analyzed electrophysiologically using middle latency auditory evoked potentials (MLAEP) and long latency (event-related potentials, P300) auditory evoked potentials. Neuropsychological testing consisted of Wisconsin Card Sorting Test (WCST). According to WCST results, patients with PD were divided into 2 subgroups: patients with normal and abnormal WCST performance (WCST(-) and WCST(+) subgroups, respectively). Sixteen of 46 patients (34.8%) showed cognitive impairment when evaluated with WCST. Statistically significant differences in middle latency auditory evoked potentials and P300 results between WCST(-) and WCST(+) groups were found consisting of P300 abnormalities in 93.8% patients in WCST(+) and 57.7% in WCST(-) group. Middle latency auditory evoked potentials were abnormal in 71.4% and 63% patients in WCST(+) and WCST(-) group, respectively. P300 was absent significantly more often (P < 0.01) in the subgroup with cognitive impairment. The difference in middle latency auditory evoked potentials results between these subgroups was statistically insignificant. The auditory evoked potentials changes were more common among patients with abnormal WCST performance. According to our results, the auditory evoked potentials of different latencies are helpful in the assessment of cognitive changes accompanying PD.
Perception of musical rhythms is culturally universal. Despite this special status, relatively little is known about the neurobiology of rhythm perception, particularly with respect to beat processing. Findings are presented here from a series of studies that have specifically examined the neural basis of beat perception, using functional magnetic resonance imaging (fMRI) and studying patients with Parkinson's disease. fMRI data indicate that novel beat-based sequences robustly activate the basal ganglia when compared to irregular, nonbeat sequences. Furthermore, although most healthy participants find it much easier to discriminate changes in beat-based sequences compared to irregular sequences, Parkinson's disease patients fail to show the same degree of benefit. Taken together, these data suggest that the basal ganglia are performing a crucial function in beat processing. The results of an additional fMRI study indicate that the role of the basal ganglia is strongly linked to internal generation of the beat. Basal ganglia activity is greater when participants listen to rhythms in which internal generation of the beat is required, as opposed to rhythms with strongly externally cued beats. Functional connectivity between part of the basal ganglia (the putamen) and cortical motor areas (premotor and supplementary motor areas) is also higher during perception of beat rhythms compared to nonbeat rhythms. Increased connectivity between cortical motor and auditory areas is found in those with musical training. The findings from these converging methods strongly implicate the basal ganglia in processing a regular beat, particularly when internal generation of the beat is required.
Several studies, including work from the Parkinson's disease (PD) non-motor group and others, have established that the non-motor symptoms of PD are common, occur across all stages of PD, are under-reported, and are a key determinant of quality of life. Research suggests that the non-motor symptoms of the disease are frequently unrecognised by clinicians and remain untreated. Even when identified, there is a common perception that many of these symptoms are untreatable. The role of dopaminergic drugs in treating the various non-motor problems of PD, although clinically recognised, has received little attention. In this Review, we investigate the dopaminergic basis of the range of non-motor symptoms that occur in PD such as depression, apathy, sleep disorders (including rapid-eye movement sleep behaviour disorder), and erectile dysfunction. We discuss the evidence that these symptoms are treatable, at least in part, with various dopaminergic strategies and, where relevant, we also refer to the use of deep-brain stimulation of appropriate targets in the brain. This Review provides a comprehensive overview of the management of this challenging aspect of PD.
Twenty Parkinson's disease (PD) patients (mean age 69.9 years) and 24 normal individuals' (mean age 63.8) both ears were investigated by brainstem auditory evoked potentials (BAEPs) and pure tone audiometry (PTA). There were no statistically significant age differences between the patients and control subjects. PTA results were significantly elevated for PD patients in 4,000 and 8,000 Hz (P < 0.05). Parkinsonian patients showed significantly increased latencies in wave V and I-V interpeak latencies (P < 0.05). The results of this study suggest that PTA and BAEPs could be affected in parkinson disease.
Numerical data from the literature on presbyacusis, in the form of pure-tone hearing threshold levels as a function of age, are subjected to critical evaluation and analysis. A formula is derived for predicting the age effect for otologically screened groups of males and females. Further, the complete distribution of hearing levels for each audiometric frequency in the range 0.125-12 kHz and at any age can be estimated with the aid of tabulated coefficients and some simple rules. The study was undertaken in connection with the work of ISO on standardization of normative audiometric data.
Rabbits were used for the long-term study of auditory function associated with experimental hypertension and hypercholesterolemia. Auditory dysfunction (threshold changes of sound evoked responses) was monitored with an electrode, chronically implanted into the contralateral inferior colliculus. Hypertension was created using the renal encapsulation technique. Auditory function in the hypertension trial demonstrated a dip at higher frequencies as well as improvement at lower frequencies. One gram of cholesterol fed daily for three months was capable of making rabbits atherosclerotic. Cholesterol-fed rabbits showed increasing auditory dysfunction over time at all frequencies. When experimental hypertension was combined with hypercholesterolemia, the auditory changes appeared additive. This work, although in preliminary stages, seems to provide experimental evidence that auditory dysfunction is associated with cholesterol diet.
The relation between central auditory processing disorders (CAPD) and age has been described in selected subjects. However, the prevalence of CAPD in the general population has not been established. We tested 1026, 64- to 93-yr-old members of the Framingham Heart Study cohort with Central Institute for the Deaf W-22 lists (CID W-22) in quiet, the Synthetic Sentence Identification test with ipsilateral competing message (SSI-ICM), and the Staggered Spondaic Word test. The presence or absence of CAPD could be established with at least one of three indices in 1018 subjects. The CID W-22 performance-intensity function rollover index was greater than 0.20 in 1.4% of 1009 subjects. The difference between maximum CID W-22 and SSI-ICM (0 dB message-to-competition ratio) scores was greater than 20% in 18.2% of 816 subjects. The Staggered Spondaic Word category was moderately, severely, over-corrected moderately, or over-corrected severely abnormal in 10.7% of 941 subjects (using 12-59-yr-olds' norms and adjusting scores when appropriate). Abnormal results on any one index occurred in 22.6% of the subjects. Thus, we conclude that the prevalence of CAPD in the elderly is less common than previous studies would suggest. Furthermore, although the rate of CAPD increased with age, age accounted for no more than 15% of the variability of any of the three indices. Therefore, its presence is dominated by factors other than chronological age.
Many studies have documented the decline in auditory function with age. We broaden that data base in this the first of a series of reports emanating from the auditory testing of the Framingham cohort during biennial exam 18. The results of the auditory questionnaire, hearing sensitivity, acoustic compliance measures, and word recognition tests obtained from 1662 men and women in their 60th through 90th decades are presented. Pure-tone thresholds increased with age but the rate of change with age did not differ by gender even though men had poorer threshold sensitivity. Maximum word recognition ability declined with age more rapidly in men than in women and was poorer in men than in women at all ages. Acoustic compliance and middle ear pressure did not vary with gender or age. Acoustic reflex thresholds to a contralateral stimulus at 1 kHz increased slightly with age, more in women than in men; ipsilateral acoustic reflex thresholds did not vary with age or gender. Hearing aids were being used in only 10% of subjects likely to benefit from amplification.
The Lewy body is a distinctive neuronal inclusion that is always found in the substantia nigra and other specific brain regions in Parkinson's disease. It is mainly composed of structurally altered neurofilament, and occurs wherever there is excessive loss of neurons. It occurs in some elderly individuals and rarely in other degenerative diseases of the central nervous system. In 273 brains of patients dying from disorders other than Parkinson's disease, the age-specific prevalence of Lewy bodies increased from 3.8% to 12.8% between the sixth and ninth decades. Associated pathological findings suggest that these cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease. In view of the common and widespread occurrence of this disorder we propose that endogenous mechanisms operating in early life may be more important than environmental agents in the pathogenesis of Lewy bodies and Parkinson's disease.
Thresholds of hearing as a function of age and sex for screened, or 'otologically normal', persons have been standardised (ISO 7029) on the basis of a study by Robinson and Sutton (1978). For purposes such as the evaluation of hearing loss due to noise exposure in industrial populations, it is not generally realistic to compare the hearing thresholds to an age-matched 'otologically normal' baseline, since the difference will include adventitious hearing loss as well as the noise-related components. This paper presents typical data for an unscreened population, in a companion form to ISO 7029. The results are derived from a critical analysis of published material and are shown to converge closely to ISO 7029 at the extremity of the distributions. Striking uniformity in the form of the distributions is revealed among apparently discordant data from different studies, showing that the adventitious hearing loss, or so-called 'pathological overlay', is essentially equivalent to accelerated ageing.
Twenty-five Parkinson's disease (PD) patients were studied by brainstem auditory evoked potentials (BAEP) with increased stimulus rate (ISR) and compared to a control age and hearing matched group. A second comparison was made between L-dopa-treated and untreated PD patients. The results of the study suggest that there is subclinical involvement of the auditory brainstem in PD patients, possibly due to the dopamine influence upon the blood vessels. Our results also indicate that dopamine is probably not involved in the synaptic transmission along the auditory pathway of the brainstem.
Anatomical studies utilizing wheat germ lectin-bound horseradish peroxidase demonstrated direct connections between the pontine parabrachial region and the substantia nigra pars reticulata and to a lesser extent, the entopeduncular nucleus as well as a number of other forebrain regions including the amygdala, hypothalamus, thalamus, bed nucleus stria terminalis and substantia innominata. The pontine parabrachial region was also shown to receive direct inputs from the spinal trigeminal system and to send axons to areas surrounding trigeminal and hypoglossal motor areas. Once the anatomical connections were determined, electrophysiological studies were undertaken to investigate some of the functional aspects of these connections between the pontine parabrachial, basal ganglia and trigeminal systems. Extracellular single unit recordings were obtained from 228 cells in the dorsal pontine parabrachial region of the cat. These cells were tested for responsiveness to trigeminal sensory stimulation and activation of basal ganglia outputs (i.e. substantia nigra and entopeduncular nucleus). Twenty-two percent of pontine parabrachial cells responded to only trigeminal stimulation; 4% responded to entopeduncular nucleus only; 37% responded to substantia nigra only, and 28% responded to both substantia nigra and trigeminal stimulation. Furthermore, 43% of pontine parabrachial cells with both substantia nigra and sensory response had the sensory response altered by a preceding stimulus to the substantia nigra. Thus, the substantia nigra is shown to exert influences on both the spontaneous activities and afferent responses of pontine parabrachial neurons. The significance of these findings are discussed in relation to the importance of descending basal ganglia influences and ascending influences from the pontine parabrachial region on various sensorimotor activities.