Abstract
The association between hearing impairment and dementia has emerged as a major public health challenge and
has triggered increasing interest with significant opportunities for earlier diagnosis, treatment and prevention.
Hearing loss appears as a risk factor for cognitive impairment, and has been identified as a potential modifiable
age-related condition linked to dementia. Midlife hearing loss, if eliminated, might decrease the risk of dementia in
the general population.
Few studies so far have examined the relationship between hearing loss and the molecular changes in the brain,
and more specifically in the hippocampus, that lead to cognitive dysfunction. This proposal puts forward several
innovative research questions to assess the relation between hearing loss, cognitive decline and dementia.
Four hypotheses on the causal relationship between peripheral hearing loss and cognitive decline have been proposed. This project considers two of these hypotheses to be tested in relevant mouse models which
will allow a direct appraisal of the impact of hearing loss on the onset and time course of cognitive decline, as well as underlying pathophysiological mechanisms.
Workpackage 1 explores the "cognitive load on perception" hypothesis by evaluating whether tau pathology induces auditory dysfunction independently of sensory deprivation. Utilizing a validated mouse model of tauopathy, auditory function will be correlated with cognitive parameters. Notably, correction of a single nucleotide variant associated with sensorineural hearing loss will enable a comprehensive study of auditory function. Additionally, the role of cadherin 23 in cognitive decline will be elucidated.
Workpackage 2 assesses the "sensory deprivation" hypothesis and investigates the impact of sensory deprivation induced by noise trauma on cognitive decline in wild-type mice. By differentiating between auditory and non-auditory effects of noise trauma, the study aims to uncover the downstream pathophysiology of noise-induced memory loss. Specifically, the involvement of cochlin expression in the hippocampus will be examined.
This project aims to unravel the molecular and cellular mechanisms underlying cognitive decline induced by inner ear dysfunction. Focus will be on neuroinflammation, oxidative stress pathways, and their impact on hippocampal neurogenesis. Microglial alterations and related neuroinflammatory processes will be studied as potential links between inner ear dysfunction, dysfunctional neurogenesis, and cognitive decline. Recognizing sexual dimorphism in auditory physiology and susceptibility to age-related hearing loss, this objective emphasizes the inclusion of both male and female subjects to capture sex-specific associations accurately.
This study aims to provide a comprehensive understanding of the complex interplay between hearing loss, cognitive decline, and tauopathy, offering insights into potential therapeutic interventions and preventive strategies for age-related cognitive disorders.
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