Mechanisms Linking Hearing Loss and Alzheimer's Disease and Related Dementias

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The proposed K23 award will provide Justin S. Golub, MD, an assistant professor of otolaryngology—head and neck surgery at Columbia University Medical Center, with mentored career development to establish an independent research career in the study of the relation of hearing loss (HL) to Alzheimer’s disease (AD) and related dementias (ADRD). Age-related HL is the third most common chronic condition in older adults and is associated with ADRD, cognitive decline, and brain atrophy. However, the mechanisms underlying these associations are unknown. The goal of this career development award is to advance Dr. Golub’s research career in HL and ADRD by (a) providing mentored career development and training in patient-oriented research (POR); and b) conducting research to elucidate the mechanisms underlying the association of HL with ADRD in an ancillary study of an ongoing project, in which the primary mentor, José Luchsinger, is the principal investigator. This project will inform the development of future POR in HL and ADRD. Career development will be provided through an experienced team of mentors spanning the disciplines of aging, geriatrics, neuropsychology, neuroimaging, epidemiology, and otolaryngology. Training will occur in 6 key areas: (1) aging and ADRD; (2) implementing hearing assessments in POR; (3) brain imaging; (4) cognitive testing; (5) biostatistics and epidemiology related to POR in ADRD; (6) professional development. Modes of learning will include meetings with mentors, formal courses in career development, formal courses in epidemiology and biostatistics, seminars in aging and ADRD, training and participation in primary data collection, scientific meetings, and training in the responsible conduct of research. Preliminary studies from the applicant revealed a 70% increased risk of ADRD in the elderly with observed (not measured) HL compared with those without observed HL. The research goal of this award is to examine the associations of objectively measured HL with imaging markers of ADRD and cognitive performance in late middle aged persons. This will be the first step towards elucidating the mechanisms of the association between age-related HL and ADRD. We will accomplish this by adding an audiometric hearing test to an existing longitudinal study of imaging markers of ADRD in late middle age. This study includes longitudinal ascertainment of AD, neurodegeneration, and cerebrovascular disease (CVD) on brain imaging, as well as cognition. AD is ascertained as whole brain amyloid β with 18F-Florbetaben positron emission tomography (PET). Neurodegeneration is ascertained as tau in inferior and medial temporal lobes with 18F-THK5351 PET, and brain atrophy with magnetic resonance imaging (MRI). CVD is ascertained as white matter hyperintensities and infarcts on MRI. Cognitive testing includes memory and executive function. We hypothesize that HL is associated with AD, neurodegeneration, and CVD, and these associations mediate the association between HL and worse cognitive performance. The proposed career development activities and research project will help propel a career to clarify whether HL is a cause, consequence, or correlate of ADRD.