Title: From ears to brains: understanding and measuring hearing impairment in dementia
Funder: Dunhill Medical Trust

Abstract: Hearing impairment has emerged as a major association of cognitive decline in dementia. Moreover, dementias commonly produce auditory symptoms: impaired auditory scene analysis is a salient early feature of Alzheimer’s disease (AD), while other diseases (notably, the ‘language-led’ dementia, progressive nonfluent aphasia (PNFA)) produce fundamental deficits of auditory processing. However, the links between dementia and hearing remain poorly understood: the relative impact of peripheral hearing loss versus auditory brain dysfunction, and how auditory deficits relate to particular dementia syndromes and to daily-life symptoms, disability and disease evolution all remain unclear. In my Fellowship, I will address these issues in well-characterised AD and PNFA cohorts, relative to matched healthy older controls. I aim to: identify specific profiles of peripheral and central auditory functions in AD and PNFA; show how auditory deficits relate to daily-life clinical measures; delineate brain atrophy profiles that underpin these deficits; and establish the extent to which particular auditory markers predict diagnosis and disease course (clinical and MRI changes) over time. I will use a customised psychoacoustic battery sampling peripheral hearing and auditory cognitive functions (including dynamic learning of degraded speech) and relate performance profiles to clinical functional ratings provided by caregivers and regional brain atrophy using voxel-based morphometry. I will quantify the biomarker potential of auditory measures against longitudinal clinical and MRI change measures at two annual time-points. Outcomes will include new markers of functional impact, functional reserve and underlying disease in people with neurodegenerative hearing impairment. In future, these could potentially inform diagnosis and therapeutic interventions.

Lay abstract: Background: the need for hearing research in dementia Hearing loss and dementia present huge health issues for our rapidly ageing population. Mounting evidence suggests that hearing loss may accelerate the onset and aggravate the course of dementia, while dementia in turn greatly magnifies the impact of hearing loss. However, we still do not understand how hearing and dementia are related. It is likely that dementia exacerbates the effects of any degree of deafness - but this is not the whole story. There are many forms of dementia: these diseases often cause degeneration of the hearing areas of the brain and affect how the brain processes sound signals arriving from the ears. In the commonest dementia (Alzheimer’s disease), people complain of difficulty understanding speech and other sounds in busy environments, from early in the illness; while another, less common dementia (primary progressive aphasia, PPA) strikes hearing and language functions as the leading problem. Improved understanding of how hearing and brain functions are linked and impact on daily life in different dementias would open up exciting opportunities. Dementia could be diagnosed via specific symptoms of hearing problems, while still at an early stage; and potentially, the progress of disease could be slowed. Hearing symptoms could be treated much more effectively: if the hearing brain is damaged in dementia, it is unlikely that conventional hearing aids alone will be the answer – successful treatment might require changes to the person’s hearing environment, communication re-training or medications. My Fellowship will tackle these problems, for the first time. I will compare ear and hearing brain functions in two major dementia diseases – Alzheimer’s and PPA – relative to healthy older people. Main aims of my project are to: 1.Identify specific changes in ear and hearing brain function in Alzheimer’s and PPA, compared with healthy older people 2.Show how particular hearing problems relate to daily life disability in these diseases 3.Show how hearing problems link to loss of brain tissue and the pattern of tissue loss on brain scans 4.Determine whether these hearing problems predict the course of the dementia disease Outline of research methodsI will use specific hearing tests to measure and compare ear and brain functions and compare these with clinical disability ratings provided by patients’ caregivers. I will then relate these measurements to changes on brain scans performed 12 months apart. Analysis of the results will allow me to identify which hearing measurements best predict disability and brain changes – and potentially, also reserve capacity that could be targeted by treatment – in different dementia diseases. People with impaired hearing will benefit in three main ways: 1.Improved recognition, diagnosis and measurement of the effects of brain diseases on hearing function 2.New tests to diagnose hearing impairment in people with dementia (potentially, more reliably than standard memory tests), enabling effective treatments to be developed and evaluated 3.Detection of hearing changes that drive daily life disability, clinical decline and brain tissue loss in cognitively impaired older people

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: EAR;NEUROLOGICAL