The cerebrovascular system: the missing link between hearing loss and dementia?
Royal National Institute for Deaf People
Institut Pasteur
Dementia is a major health challenge, as it is predicted to affect 100 million people by 2050. Hearing loss was recently shown to be a major risk factor for dementia. However, the biological mechanisms underlying this correlation are unknown. The neurovascular system plays a crucial role in the neurodegenerative pathophysiological process of dementia. Based on our ground-breaking preliminary results showing that i) the central auditory system is highly vascularised and ii) this vascularisation is strongly remodelled following peripheral hearing loss, we aim to determine whether hearing impairment increases the risk of dementia directly by affecting the vascular organisation of the central auditory system. Using mouse genetic resources for hearing impairment and 3D whole-brain imaging methods for analyses of the brain microvasculature, we will assess the impact on the cerebrovascular system of (1) peripheral hearing loss and (2) central auditory deficits in genetic forms of deafness. We will also determine (3) whether changes in the auditory neurovascular system as a result of auditory deficits are associated with an increase in the levels of markers of neurodegeneration and (4) whether hearing restoration in a genetic form of deafness rescues auditory system vascularisation defects. By characterising the cerebrovascular system as a key player in the mechanisms linking hearing impairment to dementia, our work will provide a scientific basis for evaluating the potential contribution of hearing rehabilitation to decreasing the risk of dementia, whilst identifying the cerebrovascular system as a promising therapeutic target for preventing and delaying dementia.
2.1 Biological and endogenous factors