Tinnitus and risk of Alzheimer’s and Parkinson’s disease: a retrospective nationwide population-based cohort study

Abstract

Previous studies have shown that central auditory dysfunction without severe peripheral hearing loss was associated with higher incidences of cognitive decline and Alzheimer's dementia 11,12. Both hearing loss and central auditory dysfunction are associated with higher risk of developing dementia 5-10 years later 13. Uhlmann et al. 14 demonstrated an association of hearing impairment and Alzheimer's dementia. There may be a pathophysiological interplay of hearing impairment and neurodegeneration. Although the prevalence of tinnitus is not exactly related to the prevalence of hearing loss, chronic tinnitus is usually accompanied by a hearing impairment 4. Previous research revealed that chronic tinnitus was related to the anatomical brain abnormalities, including cortical grey matter reduction and reduced white matter integrity 15. In previous decades, structural and functional brain research showed the correlation between annoying tinnitus and various forms of cognitive dysfunction, especially executive control of attention and working memory 16. Such studies suggest that changes in hearing, olfaction may antecede the beginning of cognitive impairments and dementia as the strong risk factors of AD dementia 17,18. On the other hand, adequate research shows that specific sensory changes may be early biomarkers for AD 13. Previous studies have not used population-based cohort study to evaluate the relationship between tinnitus and subsequence risk of AD and PD. We applied nationwide data from the National Health Insurance (NHI) system to operate a retrospective population-based cohort study in Taiwan. This reliable data has been used for various studies, including tinnitus and AD/PD 19-21. The hypothesis of this study is that tinnitus might be related with the likelihood of subsequent diagnosis of AD and PD. We aim to determine the possibility of an association between tinnitus and a higher risk of AD and PD development. Methods Data sources. The NHI program, an essential health insurance program instituted in 1995, provided comprehensive medical care coverage to about 99% of the residents in Taiwan, including inpatient, outpatient, emergency, and traditional Chinese medicine services 22. Comprehensive information on medical visits, including diagnostic codes and prescription details according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) are provided by the NHI Research Database (NHIRD). NHIRD is supervised by the National Health Research Institutes, with confidentiality kept in congruence with the directives of the NHI Bureau, Taiwan. Data used in the current study are from the Longitudinal Health Insurance Database 2005 (LHID2005). LHID2005 data were methodically and randomly retracted from the NHIRD, which contains data on one million people. No significant differences in the average insured payroll-related amount, sex distribution, or age distribution between patients in the LHID2005 and those in the original NHIRD were reported by NHRI 23 .

The impact of tinnitus distress on cognition

“…Tinnitus distress seems to negatively affect general or crystallized intelligence and executive functions while not influencing processing speed. This finding is novel given the nature of applied methodologies and the withingroup analysis in contrast to between-group findings of lower intelligence 27,35,37 , various impaired cognitive www.nature.com/scientificreports/ abilities except long-term memory 54 , increased risk of Alzheimer's and Parkinson's disease 55 , and lower TMT performance 27,[34][35][36] in tinnitus patients. In some studies these behavioral findings were further corroborated by neurophysiology, mostly in the form of longer latencies of standard event-related EEG components in auditory oddball tasks 54,56 .…”

Tinnitus Is Associated With Improved Cognitive Performance in Non-hispanic Elderly With Hearing Loss

“…Because of this high comorbidity, tinnitus has been often assumed to impair cognition (Hallam et al, 2004;Savastano, 2008;Tegg-Quinn et al, 2016;Chu et al, 2020;Lee, 2020). For example, Tegg-Quinn et al (2016) reviewed 18 relevant studies to show an association between tinnitus and some aspects of cognitive function, such as executive control of attention.…”

“…In a meta-analysis study involving 38 records from 1,863 participants, Clarke et al (2020) found that tinnitus is additionally associated with lower processing speed and poorer short-term memory. Based on a national population retrospective study, Chu et al (2020) showed that tinnitus is an independent risk factor for subsequent Alzheimer's and Parkinson's disease, suggesting a role of tinnitus in age-related cognitive decline.…”

An Evaluation of the Relationship between Retinal Nerve Fiber Thickness, Cochlear Nerve Thickness, the Level of Tinnitus, and Hearing Loss in Unilateral Tinnitus Patients

“…The similar results obtained in the OCT measurements suggested that there could be an underlying neurodegenerative condition and tinnitus could be the first finding of this neurodegeneration. In a recent population-based cohort study on this subject, it was reported that there could be a correlation between the presence of tinnitus and the future development of neurodegenerative diseases such as PD and AD [Chu et al, 2020]. In that study of 12,657 patients with tinnitus and 25,314 healthy individuals without tinnitus, the study participants were evaluated in respect of the development of neurodegenerative disease after a mean follow-up period of 7.42 years (range, 6.09-8.71 years).…”