Esma Idrizbegovic

Central auditory function in early Alzheimer's disease and in mild cognitive impairment.

OBJECTIVE to investigate auditory function in subjects with early Alzheimers disease, mild cognitive impairment and with subjective memory complaints, in search of signs of central auditory processing dysfunction even in early stages of cognitive impairment. DESIGN AND SUBJECTS a consecutive group of men and women, referred to the Memory Clinic at the Karolinska University Hospital, was approached for inclusion in this prospective study. One hundred and thirty-six subjects, mean age 64 years (range 50-78 years), diagnosed with Alzheimers disease (n = 43), mild cognitive impairment (n = 59) or with subjective memory complaints (n = 34), were included. METHODS auditory function was assessed with pure tone audiometry, speech perception in quiet and in background noise and dichotic digits tests with two or three digits. RESULTS pure tone audiometry and speech perception scores in quiet and in background noise were normal for age and without between-group differences. Dichotic digits tests showed strongly significant differences between the three groups, where the Alzheimers disease group performed significantly poorer than the other two groups, with the mild cognitive impairment group in an intermediate position. CONCLUSIONS our results demonstrate that central auditory processing dysfunction is highly evident in subjects with Alzheimers disease, and to a considerable extent even in subjects with mild cognitive impairment.

Presbyacusis and calcium-binding protein immunoreactivity in the cochlear nucleus of BALB/c mice

The BALB/c mouse is an established model for the early development of sensorineural hearing loss, and is homozygous for the Ahl allele (age-related hearing loss). The present study was designed to determine how auditory peripheral pathology influences calcium-binding protein immunoreactivity in the cochlear nucleus in aged BALB/c mice. To address this issue the loss of hair cells, spiral ganglion neurons (SGN), and neurons in the dorsal (DCN) and posteroventral (PVCN) cochlear nucleus of BALB/c mice at 1 and 24 months of age were quantified using CAST stereological methods. These values were then compared to the percent increase in immunopositive calcium-binding proteins in the cochlear nucleus. By 24 months of age there was a near complete loss of all outer hair cells (OHC). The inner hair cell (IHC) loss was near complete in the more apical and basal regions, while in the mid-regions approximately 50% were missing. The SGN in the apical and middle turns show a 20% loss (re: 1 month) and the basal turn up to 80% loss. A statistically significant decrease in the density of DCN and PVCN neurons (25%) was found at 24 months of age compared to the one month old animals. The percentage of parvalbumin and calretinin positive neurons in the DCN and the PVCN in relation to the density of Nissl stained neurons showed significant increases at 24 months compared to the 1 month old animals. We also determine the relationship between peripheral pathology and the percent increase in calcium-binding protein immunoreactivity. In the DCN, the percent increase of calretinin and parvalbumin was correlated to the loss of SGN, IHCs and OHCs. In the PVCN, parvalbumin was correlated to SGN, IHC, and OHC loss. The percent increase in calbindin immunoreactivity was not correlated to any peripheral pathology. The data here suggest a percent increase in calcium-binding protein immunoreactivity in the cochlea nucleus in the 24 month old mice may reflect an endogenous protective strategy that is designed to counteract calcium overload that is prominent during aging and degeneration. These results will be valuable for understanding the relationship among the peripheral and central auditory system in a model demonstrating a rapidly progressive presbyacusis.

Validation of Online Versions of Tinnitus Questionnaires Translated into Swedish

Background: Due to the lack of objective measures for assessing tinnitus, its clinical evaluation largely relies on the use of questionnaires and psychoacoustic tests. A global assessment of tinnitus burden would largely benefit from holistic approaches that not only incorporate measures of tinnitus but also take into account associated fears, emotional aspects (stress, anxiety, and depression), and quality of life. In Sweden, only a few instruments are available for assessing tinnitus, and the existing tools lack validation. Therefore, we translated a set of questionnaires into Swedish and evaluated their reliability and validity in a group of tinnitus subjects. Methods: We translated the English versions of the Tinnitus Functional Index (TFI), the Fear of Tinnitus Questionnaire (FTQ), the Tinnitus Catastrophizing Scale (TCS), the Perceived Stress Questionnaire (PSQ-30), and the Tinnitus Sample Case History Questionnaire (TSCHQ) into Swedish. These translations were delivered via the internet with the already existing Swedish versions of the Tinnitus Handicap Inventory (THI), the Hospital Anxiety and Depression Scale (HADS), the Hyperacusis Questionnaire (HQ), and the World Health Organization Quality of Life questionnaire (WHOQoL-BREF). Psychometric properties were evaluated by means of internal consistency [Cronbachs alpha (α)] and test–retest reliability across a 9-week interval [Intraclass Correlation Coefficient (ICC), Cohens kappa] in order to establish construct as well as clinical validity using a sample of 260 subjects from a population-based cohort. Results: Internal consistency was acceptable for all questionnaires (α > 0.7) with the exception of the “social relationships” subscale of the WHOQoL-BREF. Test–retest reliability was generally acceptable (ICC > 0.70, Cohens kappa > 0.60) for the tinnitus-related questionnaires, except for the TFI “sense of control” subscale and 15 items of the TSCHQ. Spearmen rank correlations showed that almost all questionnaires on tinnitus are significantly related, indicating that these questionnaires measure different aspects of the same construct. The data supported good clinical validity of the tinnitus-related questionnaires. Conclusion: Our results suggest that most Swedish adaptations of the questionnaires are suitable for clinical and research settings and should facilitate the assessment of treatment outcomes using a more holistic approach by including measures of tinnitus fears, emotional burden, and quality of life.

Short-Term Longitudinal Study of Central Auditory Function in Alzheimer's Disease and Mild Cognitive Impairment

Background/Aims: Central auditory function can be studied to monitor the progression of mild cognitive impairment to dementia. Our aim was to address this issue in a prospective longitudinal setting. Methods: Tests of central hearing function were performed on 70 subjects with either Alzheimers disease (AD) or mild cognitive impairment, and in controls with subjective memory complaints but normal cognition. The time span until follow-up was 1.5 years. Results: The dichotic digit free recall test showed a significant decline in the AD group compared with the controls (left ear). Conclusion: The short time span was long enough to disclose a central auditory processing decline in AD.

The effect of intravenously administered mexiletine on tinnitus-a pilot study

The effect of intravenously administered mexiletine on subjective tinnitus and hearing was studied in six patients, who initially responded positively to lidocaine. Distinct mexiletine-induced decreases in tinnitus loudness were demonstrated in three subjects, as reflected by maximum VAS (visual analogue scale) level reduction of 34%, 95%, and 100%, respectively. One subject reported change in tinnitus pitch, another one showed a slight (18% on VAS) tinnitus reduction, and one subject disclosed no effect. Side effects were seen only during one of seven infusions. Mexiletine induced shifts in pure-tone threshold, transient evoked otoacoustic emission, and acoustic reflex threshold, probably reflecting a reversible interference in the function of organ of Corti. The concentration effect relationship remained unclear and no general ‘therapeutic’ level could be identified. This study confirms the effect of mexiletine on the auditory function and its potential as a possible therapeutic agent or a model for further development in tinnitus pharmacotherapy.

Quinine-induced hearing loss in the guinea pig is not affected by the Ca2+ channel antagonist verapamil

It is well documented that quinine induces reversible hearing loss and tinnitus. The purpose in this study was to induce a quinine hearing loss and to investigate if verapamil, a Ca2+ channel antagonist of L-type might affect the response. Pigmented guinea pigs (n = 24) were anaesthetized by atropine. Hypnorm and midazolam but permitting spontaneous respiration. An electrode of platinum was placed on the round window and short (10 msec) tone pulses at 8 kHz were presented to the external ear. A typical deflection of the N1-wave was determined as the hearing threshold. Quinine hydrochloride 40 mg/kg and verapamil 1 mg/kg were given intravenously. Quinine induced a significant and reversible hearing loss (mean 16 dB). This hearing loss was not at all affected by verapamil given before or after quinine. Verapamil often caused acute cardiac arrest and particularly the combination verapamil followed by quinine-induced death to the animal. We conclude that verapamil and quinine had no in vivo interaction with regard to the hearing ability.

Otological diagnoses and probable age-related auditory neuropathy in “younger” and “older” elderly persons

Abstract Objective: Audiological data from a population based epidemiological investigation were studied on elderly persons. Specific diagnoses of otological and audiological disorders, which can result in hearing loss, were searched for. Design: A retrospective register study. Study sample: Three age cohorts, 474 70- and 75-year olds (“younger”), and 252 85-year olds (“older”), were studied. Clinical pure tone and speech audiometry was used. Data from medical files were included. Results: Conductive hearing loss was diagnosed in 6.1% of the “younger” elderly persons, and in 10.3% of the “older” ones. Specific diagnoses (chronic otitis media and otosclerosis) were established in about half of the cases. Sensorineural hearing loss, other than age-related hearing loss and noise induced hearing loss, was diagnosed in 3.4 % and 5.2% respectively. Severely impaired speech recognition, possibly reflecting age-related auditory neuropathy, was found in 0.4% in the “younger” group, and in 10% in the “older” group. Bilateral functional deafness was present in 3.2% of the 85-year-old persons, but was not present in the 70–75-year group. Conclusion: The incidence of probable age-related auditory neuropathy increases considerably from 70–75 to 85 years. There are marked differences between “younger” and “older” elderly persons regarding hearing loss that severely affects oral communication. Sumario Objetivo: Se estudiaron los datos audiológicos obtenidos en una investigación epidemiológica basada en grupos de ancianos. Se buscaron diagnósticos específicos de problemas otológicos o audiológicos que pueden determinar pérdidas auditivas. Diseño: Estudio retrospectivo de registros. Muestra: Se estudiaron tres cohortes de grupos de edad: 474 “jóvenes” de 70 y 75 años y 252 “viejos” de 85 años de edad. Se realizó audiometría clínica por tonos puros y logoaudiometría. Se incluyeron los datos de los expedientes clínicos. Resultados: Se diagnosticó pérdida auditiva conductiva en el 6.1% de los ancianos “jóvenes” y en el 10.3% de los “viejos”. Se estableció el diagnóstico especifico (otitis media crónica y otoesclerosis) en cerca de la mitad de los casos. Se diagnosticó pérdida auditiva neurosensorial, aparte de pérdidas relacionadas con la edad o inducidas por ruido, en el 3.4% y en el 5.2% de los casos, respectivamente. Se encontró reconocimiento del lenguaje severamente afectado, posiblemente reflejando neuropatía auditiva relacionada con la edad, en el 0.4% de los “jóvenes” y en el 10% de los “viejos”. La sordera funcional bilateral estuvo presente en el 3.2% de las personas de 85 años, pero no se observó en el grupo de personas de 70–75 años. Conclusión: La incidencia de neuropatía auditiva probablemente relacionada con la edad, aumenta considerablemente de los 70–75 a los 85 años. Hay marcadas diferencias relacionadas con las pérdidas auditivas entre ancianos más “jóvenes” y más “viejos”, que afectan severamente la comunicación oral.

Mismatch Negativity and Ear Laterality in Alzheimer’s Disease and in Mild Cognitive Impairment

BACKGROUND Cortical auditory event-related potentials (ERPs) were studied in order to measure mismatch negativity (MMN). Three groups of subjects were studied: patients with Alzheimers disease (AD, n = 32), mild cognitive impairment (MCI, n = 44), and subjective memory complaints without cognitive decline (SMC, n = 27). A bottom up strategy was applied, and the right and left ears were stimulated monaurally. OBJECTIVE To investigate MMN in AD and MCI, and in a clinical reference group. METHODS ERPs were carried out with 500 tone pulses at 80 dBnHL. Each sequence included 80% standard tones (500 Hz) (f), and 20% deviant tones (1000 Hz) (r). MMN measurements were carried out by comparing the amplitudes of (f) and (r) recordings and to calculate the amplitude difference in μV for each group. The right and the left ears were analyzed separately. RESULTS A left ear advantage (LEA) of MMN amplitude was demonstrated in the two groups with better cognition (the MCI and the SMC groups), but not in the AD group. DISCUSSION The absence of MMN asymmetry in the AD group is possibly caused by a dysfunction to apprehend changes of tonal stimuli.

Dietary habits and hearing

Abstract Objective: Study groups from three age cohorts of 70–75 year-olds were investigated to search for possible correlations between dietary habits and auditory function. Design: A cross-sectional, epidemiological study. Study sample: A total number of 524 people (275 women, 249 men) were recruited from three age cohorts. The study sample was representative of the general population. All participants answered a diet history and were tested with pure-tone audiometry. Eleven categories of food consumption were related to pure-tone averages of low-mid frequency hearing, and high frequency hearing. Results: Two consistent correlations between diet and hearing were observed. One was a correlation between good hearing and a high consumption of fish in the male group. The other was a correlation between poor high frequency hearing and a high consumption of food rich in low molecular carbohydrates in both genders; a larger effect size was seen in females. Conclusions: The study indicates that diet is important for aural health in aging. According to this study fish is beneficial to hearing, whereas consumption of “junk food”, rich in low molecular carbohydrates, is detrimental. Other correlations, e.g. between high consumption of antioxidants, were not demonstrated here, but cannot be excluded.

A Longitudinal Study of Peripheral and Central Auditory Function in Alzheimer’s Disease and in Mild Cognitive Impairment

Background/Aim: Central auditory processing disorder (CAPD) might precede the onset of Alzheimer’s disease (AD). A method of evaluating CAPD is the dichotic digits test (DDT). The aim was to address this in a longitudinal setting. Methods: A total of 136 individuals were assessed with peripheral and central hearing tests at baseline and at 5-year follow-up. Results: Subjects with AD showed a significant decline in DDT scores of the right ear from baseline to follow-up. The other groups retained high DDT scores. Peripheral auditory function declined as expected according to age. Conclusions: Our study indicates that DDT performance reflects an ongoing process resulting in dementia.