Abstract
PurposeHearing loss (HL) is one of the most common age-related diseases. Here, we investigate the central auditory correlates of HL in people with normal cognition and mild cognitive impairment (MCI) and test their association with genetic markers with the aim of revealing pathogenic mechanisms. MethodsBrain glucose metabolism based on FDG-PET, self-reported HL status, and genetic data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. FDG-PET data was analysed from 742 control subjects (non-HL with normal cognition or MCI) and 162 cases (HL with normal cognition or MCI) with age ranges of 72.2 ± 7.1 and 77.4 ± 6.4, respectively. Voxel-wise statistics of FDG uptake differences between cases and controls were computed using the generalised linear model in SPM12. An additional 1515 FDG-PET scans of 618 participants were analysed using linear mixed effect models to assess longitudinal HL effects. Furthermore, a quantitative trait genome-wide association study (GWAS) was conducted on the glucose uptake within regions of interest (ROIs), which were defined by the voxel-wise comparison, using genotyping data with 5,082,878 variants available for HL cases and HL controls (N = 817). ResultsThe HL group exhibited hypometabolism in the bilateral Heschl’s gyrus (kleft = 323; kright = 151; Tleft = 4.55; Tright = 4.14; peak Puncorr < 0.001), the inferior colliculus (k = 219;T = 3.53; peak Puncorr < 0.001) and cochlear nucleus (k = 18;T = 3.55; peak Puncorr < 0.001) after age correction and using a cluster forming height threshold P < 0.005 (FWE-uncorrected). Moreover, in an age-matched subset, the cluster comprising the left Heschl’s gyrus survived the FWE-correction (kleft = 1903; Tleft = 4.39; cluster PFWE-corr = 0.001). The quantitative trait GWAS identified no genome-wide significant locus in the three HL ROIs. However, various loci were associated at the suggestive threshold (p < 1e-05). ConclusionCompared to the non-HL group, glucose metabolism in the HL group was lower in the auditory cortex, the inferior colliculus, and the cochlear nucleus although the effect sizes were small. The GWAS identified candidate genes that might influence FDG uptake in these regions. However, the specific biological pathway(s) underlying the role of these genes in FDG-hypometabolism in the auditory pathway requires further investigation.
Highlights
Hearing loss affects millions of people around the world and The Global Burden of Disease Study found that hearing loss is the fourth leading cause of disability globally (Cunningham and Tucci, 2017; World Health Organization, 2018)
The primary goal of Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be com bined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s disease (AD)
Cognitive status of subjects in our study within non-Hearing loss (HL) comprised of 71% with MCI and 29% healthy cognition, whereas in HL, 67% of subjects had MCI and 33% were HC
Summary
Hearing loss affects millions of people around the world and The Global Burden of Disease Study found that hearing loss is the fourth leading cause of disability globally (Cunningham and Tucci, 2017; World Health Organization, 2018). Presbycusis, or age-related hearing loss (ARHL), is the most prevalent form of hearing loss which affects 80% of adults over the age of 70 years (Mares-perlman and Nondahl, 1998) It is characterised by reduced bilateral hearing sensitivity, impaired locali zation of sound sources, decreased ability to understand speech in background noise, and slowed central processing of acoustic input (Gates and Mills, 2005). It is caused by dysfunction in the transduction of sound-induced vibrations into electrical signals by sensory hair cells in the cochlea and central nervous system dysfunction in auditory signal pathway the respective contribution of central and peripheral pathologies remain unclear (Shen, 2018; Liberman, 2017). In midlife, hearing loss is the greatest modifiable risk factor for dementia, alongside hypertension and obesity early intervention might help in delaying or reducing the risk of developing dementia in later life (Livingston et al, 2020)
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