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      Age-Related Hearing Loss Associations With Changes in Brain Morphology

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          Abstract

          Age-related hearing loss has been associated with varied auditory cortex morphology in human neuroimaging studies. These findings have suggested that peripheral auditory system declines cause changes in brain morphology but could also be due to latent variables that affect the auditory periphery and brain. The current longitudinal study was designed to evaluate these explanations for pure-tone threshold and brain morphology associations. Thirty adults (mean age at Time 1 = 64.12 ± 10.32 years) were studied at two time points (average duration between visits = 2.62 ± 0.81 years). Small- to medium-effect size associations were observed between high-frequency pure-tone thresholds and auditory cortex gray matter volume at each time point. Although there were significant longitudinal changes in low- and high-frequency hearing measures and brain morphology, those longitudinal changes were not significantly correlated across participants. High-frequency hearing measures at Time 1 were significantly related to more lateral ventricle expansion, such that participants with higher measures exhibited larger increases in ventricle size. This ventricle effect was statistically independent of high-frequency hearing associations with auditory cortex morphology. Together, these results indicate that there are at least two mechanisms for associations between age-related hearing loss and brain morphology. Potential explanations for a direct hearing loss effect on brain morphology, as well as latent variables that likely affect both the inner ear and brain, are discussed.

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          Neuroanatomical changes due to hearing loss and chronic tinnitus: a combined VBM and DTI study.

          Subjective tinnitus is the perception of sound in the absence of an external source. Tinnitus is often accompanied by hearing loss but not everyone with hearing loss experiences tinnitus. We examined neuroanatomical alterations associated with hearing loss and tinnitus in three groups of subjects: those with hearing loss with tinnitus, those with hearing loss without tinnitus and normal hearing controls without tinnitus. To examine changes in gray matter we used structural MRI scans and voxel-based morphometry (VBM) and to identify changes in white matter tract orientation we used diffusion tensor imaging (DTI). A major finding of our study was that there were both gray and white matter changes in the vicinity of the auditory cortex for subjects with hearing loss alone relative to those with tinnitus and those with normal hearing. We did not find significant changes in gray or white matter in subjects with tinnitus and hearing loss compared to normal hearing controls. VBM analysis revealed that individuals with hearing loss without tinnitus had gray matter decreases in anterior cingulate and superior and medial frontal gyri relative to those with hearing loss and tinnitus. Region-of-interest analysis revealed additional decreases in superior temporal gyrus for the hearing loss group compared to the tinnitus group. Investigating effects of hearing loss alone, we found gray matter decreases in superior and medial frontal gyri in participants with hearing loss compared to normal hearing controls. DTI analysis showed decreases in fractional anisotropy values in the right superior and inferior longitudinal fasciculi, corticospinal tract, inferior fronto-occipital tract, superior occipital fasciculus, and anterior thalamic radiation for the hearing loss group relative to normal hearing controls. In attempting to dissociate the effect of tinnitus from hearing loss, we observed that hearing loss rather than tinnitus had the greatest influence on gray and white matter alterations. Copyright © 2010 Elsevier B.V. All rights reserved.
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            DNA methylation analysis on purified neurons and glia dissects age and Alzheimer’s disease-specific changes in the human cortex

            Background Epigenome-wide association studies (EWAS) based on human brain samples allow a deep and direct understanding of epigenetic dysregulation in Alzheimer’s disease (AD). However, strong variation of cell-type proportions across brain tissue samples represents a significant source of data noise. Here, we report the first EWAS based on sorted neuronal and non-neuronal (mostly glia) nuclei from postmortem human brain tissues. Results We show that cell sorting strongly enhances the robust detection of disease-related DNA methylation changes even in a relatively small cohort. We identify numerous genes with cell-type-specific methylation signatures and document differential methylation dynamics associated with aging specifically in neurons such as CLU, SYNJ2 and NCOR2 or in glia RAI1,CXXC5 and INPP5A. Further, we found neuron or glia-specific associations with AD Braak stage progression at genes such as MCF2L, ANK1, MAP2, LRRC8B, STK32C and S100B. A comparison of our study with previous tissue-based EWAS validates multiple AD-associated DNA methylation signals and additionally specifies their origin to neuron, e.g., HOXA3 or glia (ANK1). In a meta-analysis, we reveal two novel previously unrecognized methylation changes at the key AD risk genes APP and ADAM17. Conclusions Our data highlight the complex interplay between disease, age and cell-type-specific methylation changes in AD risk genes thus offering new perspectives for the validation and interpretation of large EWAS results. Electronic supplementary material The online version of this article (10.1186/s13072-018-0211-3) contains supplementary material, which is available to authorized users.
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              The Neural Consequences of Age-Related Hearing Loss.

              During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension.
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                Author and article information

                Journal
                Trends Hear
                Trends Hear
                TIA
                sptia
                Trends in Hearing
                SAGE Publications (Sage CA: Los Angeles, CA )
                2331-2165
                18 June 2019
                Jan-Dec 2019
                : 23
                : 2331216519857267
                Affiliations
                [1 ]Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA
                Author notes
                [*]Mark A. Eckert, Hearing Research Program, Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, MSC 550, Charleston, SC 29425, USA. Email: eckert@ 123456musc.edu
                Author information
                https://orcid.org/0000-0001-9286-7717
                https://orcid.org/0000-0002-3621-2043
                Article
                10.1177_2331216519857267
                10.1177/2331216519857267
                6585256
                31213143
                639ea6c0-b4a2-41ba-b2de-bf8bda93a129
                © The Author(s) 2019

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 5 January 2019
                : 12 March 2019
                : 9 May 2019
                Funding
                Funded by: National Institute on Deafness and Other Communication Disorders, FundRef https://doi.org/http://doi.org/10.13039/100000055;
                Award ID: P50 DC 000422
                Funded by: National Center for Research Resources, FundRef https://doi.org/http://doi.org/10.13039/100000097;
                Award ID: C06 RR14516
                Award ID: UL1 RR029882
                Categories
                Original Article
                Custom metadata
                January-December 2019

                presbyacusis,pure-tone thresholds,morphometry,auditory cortex,lateral ventricle

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