Hearing loss and dementia: uncovering the mechanisms of accelerated cognitive decline using comorbid preclinical models
Royal National Institute for Deaf People
Western University
Hearing loss is one of the most prevalent, chronic health conditions worldwide. In addition to age-related hearing impairment, excessive noise exposure is a leading cause of hearing loss. Beyond the devastating effects of hearing impairment itself, there is epidemiological evidence linking hearing loss to an increased risk for dementia, including Alzheimer’s disease (AD). At present, however, we lack a full understanding of the cellular mechanisms responsible for the relationship between hearing loss and dementia, which has hindered our ability to intervene effectively. Although neuroinflammation, as evidenced by activated microglia, has been identified as a key pathological correlate of both noise-induced hearing loss and age-related cognitive decline, its role as a common mechanistic link between hearing loss and dementia has not been elucidated. To that end, we will noise expose young adult male and female wildtype (Aim 1) and transgenic rats that represent a model for prodromal AD (Aim 2), and use a novel combination of (1) PET/MRI scans for neuroinflammation, (2) blood biomarker assays of pro/anti-inflammatory cytokines, (3) cognitive behavioural testing, and finally (4) post-mortem neurohistological analyses of microglial activation and AD-related pathology. By correlating these complementary results from the same rats, we will gain crucial insight into the cellular mechanisms underlying how hearing loss alters cognition throughout aging, and affects the susceptibility to AD-related pathology. Furthermore, our innovative proposal will establish a preclinical model capable of capturing the earliest interactions between hearing loss and dementia; a translational platform which could further inform future clinical investigations.
2.1 Biological and endogenous factors