An emerging Alzheimer's disease risk factor: An investigation of hearing impairment, hippocampal function, and memory in middle-aged and older adults

University Of California, San Diego, La Jolla CA

Investigators

Abstract

PROJECT SUMMARY The purpose of this proposal is to investigate the association between hearing impairment and hippocampal function, and how this association relates to memory function, in cognitively normal middle-aged and older adults. Hearing impairment has been identified as a modifiable risk factor for Alzheimer’s disease and dementia, however the mechanism for this is unknown. The central hypothesis in this proposal is that hearing impairment is associated with poorer hippocampal function and memory, and that differences in memory are mediated by hippocampal function. This hypothesis is informed by the current literature, which shows reduced hippocampal volume in humans and reduced plasticity in animal models with impaired hearing. However, the relationship between hippocampal function and hearing impairment in humans has not yet been explored. Aims 1 and 2 of this proposal will use data from the UK Biobank to investigate the association between hearing impairment and hippocampal activity, and their relationship with memory. The dataset includes: 1) hearing ability categorized into impaired and unimpaired; 2) functional MRI of hippocampal activation; and 3) memory performance assessed by a Paired Associates task. There is also evidence from animal models to suggest that hearing impairment and Alzheimer’s pathology may exert a compounding effect on hippocampal function, but this also has not been examined in humans. Therefore, Aim 3 will collect pilot data to examine associations between hearing impairment, fMRI hippocampal activation, amyloid-beta deposition, and memory performance in 30 cognitively normal older adults. The findings from this work will provide critical evidence for existing theories on the association between hearing impairment and dementia risk and will inform future hearing-based interventions. Importantly, this work will highlight the need to treat hearing impairment as part of a comprehensive approach to reducing Alzheimer’s disease risk. The Principal Investigator, Dr. Megan Fitzhugh, is currently a postdoctoral scholar at the University of California San Diego (UCSD). Previously, she conducted studies investigating sex differences in the association between hearing impairment and dementia risk, and studies of longitudinal changes in brain volume and functional connectivity associated with hearing impairment. Her career goal is to become leading investigator at the intersection of auditory neuroscience and Alzheimer’s disease, focusing on risk factors of Alzheimer’s disease, such as hearing impairment. Toward this goal, Dr. Fitzhugh’s career development efforts during this award will be dedicated toward four areas: advanced statistical methods, audiology, Alzheimer’s disease and dementia, and mentorship. UCSD is an ideal location for career development due to the expertise and multidisciplinary nature of the Department of Neurosciences and its associated Shiley-Marcos Alzheimer’s Disease Research Center and the Alzheimer’s Disease Cooperative Study. This proposal will position the PI to begin an independent research career and successfully submit an R01 proposal in a faculty position.