Prognostic Value of a Test of Central Auditory Function in Conversion from Mild Cognitive Impairment to Dementia.

BACKGROUND/OBJECTIVE: It has been suggested that central auditory processing dysfunction might precede the development of cognitive decline and Alzheimer's disease (AD). The Dichotic Digits Test (DDT) has been proposed as a test of central auditory function. Our objective was to evaluate the predictive capacity of the DDT in conversion from mild cognitive impairment (MCI) to dementia. METHODS: A total of 57 participants (26 females) with MCI were tested at baseline with pure tone audiometry, speech in quiet and in noise, and the DDT. The cognitive outcome was retrieved from medical files after 5 years. Groupwise comparisons of the baseline DDT scores were performed and the relative risk was calculated. RESULTS: Altogether 22 subjects developed any kind of dementia. Of the original 57 individuals within the MCI group, 15 developed AD and 7 developed other types of dementia. There was no significant difference in baseline DDT scores between the participants who converted to AD and those who did not. However, the group who developed other types of dementia (especially frontotemporal dementia) had lower DDT scores in the left ear than those participants who did not develop dementia. With a baseline DDT score below 50% correct responses, the participants diagnosed with MCI had a 2.49-times-higher risk of developing dementia than those with scores of 50% or better. CONCLUSION: The DDT as a central auditory test may be suitable when evaluating cognitive decline.

Dietary habits and hearing.

UNLABELLED: 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.

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

OBJECTIVE: to investigate auditory function in subjects with early Alzheimer's 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 Alzheimer's 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 Alzheimer's 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 Alzheimer's disease, and to a considerable extent even in subjects with mild cognitive impairment.

Otological diagnoses and probable age-related auditory neuropathy in "younger" and "older" elderly persons.

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.

Tinnitus distress, anxiety, depression, and hearing problems among cochlear implant patients with tinnitus.

BACKGROUND: While several studies have investigated the presence and annoyance of tinnitus in cochlear implant (CI) recipients, few studies have probed the handicap experienced in association with tinnitus in this population. PURPOSE: The aim of this study was to use validated self-report measures in a consecutive sample of CI patients who reported tinnitus in order to determine the extent of tinnitus handicap. RESEARCH DESIGN: In a retrospective design, a total of 151 patients (80% response rate) responded to a postal questionnaire, and of these, 111 (74%) reported that they currently experienced tinnitus and were asked to complete the full questionnaire. Sampling was performed at a point of a mean 2.9 years postsurgery (SD = 1.8 years). Three established self-report questionnaires were included measuring tinnitus handicap (Tinnitus Handicap Inventory [THI]), hearing problems (Gothenburg Profile), and finally, a measure of anxiety and depression (Hospital Anxiety and Depression Scale). We analyzed the data by means of Pearson product moment correlations, t-tests, ANOVAs, and chi-square. RESULTS: Data from the validated questionnaires showed relatively low levels of tinnitus distress, moderate levels of hearing problems, and low scores on the anxiety and depression scales. Using the criteria proposed for the THI (which was completed by 107 patients), 35% (N = 38) had a score indicating "no handicap," 30% (N = 32) "mild handicap" 18% (N = 19) "moderate handicap", and 17% (N = 18) "severe handicap." Thus 37 individuals from the total series of 151 reported moderate to severe tinnitus handicap (24.5%). Tinnitus distress was associated with increased hearing problems, anxiety, and depression. CONCLUSION: Tinnitus can be a significant problem following CI, but that the experienced distress is often moderate. However, a quarter of CI recipients do demonstrate moderate/severe tinnitus handicap, and thus are candidates for tinnitus specific therapy. The level of tinnitus handicap is associated with hearing problems and psychological distress.

Association of Genetic vs Environmental Factors in Swedish Adoptees With Clinically Significant Tinnitus.

Importance: No effective treatments are currently available for severe tinnitus, which affects 1% of the population and lowers the quality of life. The factors that contribute to the transition from mild to severe tinnitus are poorly known. Before performing genetic analyses and determining the mechanisms involved in the development of severe tinnitus, its heritability needs to be determined. Objectives: To examine whether clinically significant tinnitus is associated with genetic factors and to evaluate the genetic risk in the transmission of tinnitus using adoptees. Design, Setting, and Participants: Data from adoptees and their biological and adoptive parents from Swedish nationwide registers were collected from January 1, 1964, to December 31, 2015, and used to separate genetic from environmental factors in familial clustering. In all, 11 060 adoptees, 19 015 adoptive parents, and 17 025 biological parents were investigated. The study used a cohort design and a case-control approach to study genetic and nongenetic factors in tinnitus among adoptees. Main Outcomes and Measures: The primary outcome was odds ratio (OR) of tinnitus in adoptees with at least 1 affected biological parent compared with adoptees without any affected biological parent using logistic regression. The secondary outcome was OR in adoptees with at least 1 affected adoptive parent compared with adoptees without any affected adoptive parent. Results: A total of 1029 patients (440 [42.8%] male; mean [SD] age, 62 [14] years) with tinnitus were identified. The prevalence of diagnosed tinnitus was 2.2%. The OR for tinnitus was 2.22 for adoptees (95% CI, 1.03-4.81) of biological parents diagnosed with tinnitus, whereas the OR was 1.00 (95% CI, 0.43-2.32) for adoptees from adoptive parents diagnosed with tinnitus. Mean (SE) heritability determined using tetrachoric correlations was 31% (14%). Conclusions and Relevance: The findings suggest that genetic factors are associated with the familial clustering of clinically significant tinnitus with no shared-environment association, revealing that the transition from negligible to severe tinnitus may be associated with genetic factors. These findings may provide insight for future genetic analyses that focus on severe tinnitus.

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.

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.

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 Alzheimer's 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.

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 [Cronbach's alpha (α)] and test-retest reliability across a 9-week interval [Intraclass Correlation Coefficient (ICC), Cohen's 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.

Age-related increases in calcium-binding protein immunoreactivity in the cochlear nucleus of hearing impaired C57BL/6J mice.

Aging C57BL/6J (C57) mice (1-30 months old), were used to study calcium-binding protein immunoreactivity (parvalbumin, calbindin and calretinin) in the cochlear nucleus. A quantitative stereological method, the optical fractionator was used to determine the total number of neurons, and the total number of immunostained neurons in the posteroventral- and dorsal cochlear nuclei (PVCN and DCN). A statistically significant age-related decrease of the total number of neurons was found in the PVCN and DCN using Nissl staining. In the DCN, an age-related increase in the total number of parvalbumin-positive neurons was found, while no changes in the total number of calbindin or calretinin positive neurons were demonstrated. In the PVCN, the total number of parvalbumin, calbindin, or calretinin positive neurons remained stable with increasing age. The percentage of parvalbumin, calbindin, and calretinin positive neurons significantly increased in the DCN, and the percentage of parvalbumin and calbindin-positive neurons increased in the PVCN. These findings imply that there is a relative up-regulation of calcium-binding proteins in neurons that had not previously expressed these proteins. This plastic response in the profoundly hearing impaired C57 mouse may be a survival strategy for cochlear nucleus neurons.

Auditory peripheral influences on calcium binding protein immunoreactivity in the cochlear nucleus during aging in the C57BL/6J mouse.

The C57BL/6J (C57) mouse was selected as a suitable model for early presbyacusis to determine if there were correlations between peripheral pathology (spiral ganglion loss, inner and outer hair cell loss) and calcium binding immunoreactivity in the cochlear nucleus during aging. The quantitative stereological method, the optical fractionator, was used for determining the total number of neurons and calcium binding immunopositive neurons (calbindin, parvalbumin and calretinin) during aging in the posteroventral- and dorsal cochlear nucleus (PVCN and DCN) in C57 mice. Comparing 30-month-old to 1-month-old C57 mice, a percent increase in parvalbumin and calbindin immunoreactivity was evident in both the PVCN and DCN. Correlations were made between peripheral pathology (spiral ganglion and inner and outer hair cell loss) and calcium binding protein expression. Significant correlations between cochlear pathology and the percentage of parvalbumin and calretinin immunoreactive neurons were demonstrated in the DCN. Moreover, significant correlations were found between cochlear pathology and parvalbumin and calbindin in the PVCN. In summary, the findings imply that degenerative changes in the auditory periphery can modulate neuronal homeostasis by increasing calcium binding proteins in the PVCN and DCN during aging. Taken together, these findings suggest a role for calcium binding proteins in protecting against age-induced calcium toxicity.

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 Alzheimer's 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.