Glucose hypometabolism in the Auditory Pathway in Age Related Hearing Loss in the ADNI cohort.

PURPOSE: Hearing 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. METHODS: Brain 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). RESULTS: The 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). CONCLUSION: Compared 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.