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

Validation of Online Versions of Tinnitus Questionnaires Translated into Swedish

BackgroundDue 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. MethodsWe 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.ResultsInternal 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 >.70, Cohens Kappa >.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. ConclusionOur 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

Calcium binding protein immunoreactivity in the central auditory system and correlations with the auditory periphery : The effects of noise and aging in mice

This study has examined how calcium binding protein immunoreactivity is modulated in the cochlear nucleus and the inferior colliculus after noise exposure and during aging in mice. The effect of noise exposure on calbindin-D28k (calbindin) and parvalbumin immunoreactivity in the dorsal and posteroventral cochlear nucleus (DCN and PVCN) and inferior colliculus (IC) was studied in CBA/CBA mice by using two-dimensional quantification. Moderate sound stimulation caused a graded increase in the expression of calbindin and parvalbumin immunoreactivity in the DCN and IC, and parvalbumin immunoreactivity in the PVCN. This increased immunoreactivity related to sound exposure suggests the appearance of additional neurons which express these proteins after sound stimulation. These findings implicate that these neurons have the possibility to react against trauma, and display calbindin or parvalbumin as a rescue event. The effect of aging on parvalbumin, calbindin-D28k, and calretinin immunoreactivity, as well as the total neuronal number in the DCN and PVCN in aging CBA/CaJ (CBA) and C57BL/6J (C57) mice was studied. The CBA mouse strain is a useful model of late-onset presbyacusis, while the C57 mouse strain makes an excellent model of the early-onset of age-related sensorineural hearing loss. By using the unbiased quantitative stereological method, the total neuronal number and the total number of these calcium binding proteins has been determined in the DCN and PVC. An agerelated increase in the total number of parvalbumin and calbindin immunopositive neurons was demonstrated in the DCN at a time when a significant loss of neurons is noticed in the same region in CBA mice. Furthermore, an age- related increase of parvalbumin in the PVCN was observed, while the total number did not differ between young and old CBA mice. The mechanisms by which these calcium binding proteins may affect neurons during aging are not known, but it is presumably that impaired Ca2+ homeostasis might have a critical role in the cellular aging process. In C57 mice, an age-related decrease in the total number of neurons in the PVCN and DCN was found, without any significant changes in the total number of these calcium binding proteins. On the other hand, an increase of the percentage of parvalbumin in the PVCN and DCN, calbindin in the PVCN, and calretinin in the DCN was demonstrated. The reason for this increase might be because of the new synthesis of these calcium binding proteins in the previously 'silent' neurons, due to age-related alterations in Ca2+ homeostasis. Peripheral pathology was correlated to the percentage of pavalbumin, calbindin and calretinin immunopositive neurons in the DCN and PVCN in aging CBA and C57 mice. A progressive peripheral cell loss was reflected in an increased expression of parvalbumin and calretinin in the DCN of CBA mice and C57 mice. Interestingly, a major difference between CBA and C57 mice was demonstrated in the PVCN, where only C57 mice showed a positive correlation between the percentage of calbindin in the PVCN and the progressive degenerative changes in the auditory periphery. These findings imply that the pathophysiological status of the auditory periphery may influence the neuronal homeostasis in the cochlear nucleus

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

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

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.