Evaluating the associations of hearing loss with cognitive and brain health outcomes in midlife

Project Summary Emerging evidence suggests hearing loss may be a modifiable risk factor for Alzheimer's disease (AD) and related dementias (ADRD). Midlife (ages 45-65) could be a critical period when screening and intervention to prevent AD/ADRD may be most effective. Indeed, increasing evidence suggests there are detectable changes

in midlife cognition and brain health associated with risk factors, such as vascular disease, which may presage an increased risk for dementia in late life. Age-related hearing loss also often begins in midlife. As such, the recent Lancet commission on dementia prevention highlighted hearing loss in midlife as a target for dementia

prevention. However, prior investigations have focused on hearing loss and cognition in older adults. There is a critical gap of knowledge as to whether hearing loss is associated with cognition or markers of brain health in middle-aged adults. There is also a critical gap in studies on hearing loss and cognition in underrepresented

populations, subgroups at higher risk for AD/ADRD, and the intersection with social determinants of health. Addressing these gaps would inform intervention strategies targeting hearing loss, AD/ADRD risk, and health inequities. We have an exciting and unique opportunity to study the relationship between hearing loss and

midlife cognition and brain health in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CARDIA is a biracial study of Black and White men and women with a spectrum of educational attainment with measures of audiometric hearing loss, a standardized cognitive battery, and structural brain MRI from the most

recent exam, when participants had a mean age of 60. The goal of this study is to clarify the associations of hearing loss with cognitive and brain aging in middle-aged adults. In Aim 1, we will test whether pure tone audiometric hearing loss is associated with cognitive test scores, including methods to account for potential

cognitive testing error due to hearing loss. In Aim 2 we will examine the association of hearing loss with cognition among subpopulations with differing background risk of AD/ADRD. Primary subgroups will be defined by race, sex, and APOE genotype; we will also explore subgroups by education, income, and social isolation.

In Aim 3, we will investigate whether hearing loss is associated with brain volumes linked to higher AD/ADRD risk (e.g., hippocampus and white matter hyperintensities). We propose a cost-efficient study that will link newly collected objective hearing tests with cognitive and brain MRI assessments in a well-characterized and

diverse midlife cohort. Identifying associations between midlife hearing loss and cognition and brain MRI would offer an important avenue for prevention and risk stratification. Importantly, this project will help lay the groundwork for future studies evaluating the role of midlife risk factors for AD/ADRD and identifying

intervention targets to prevent cognitive decline.