Ethanol-metabolizing genes and the relationship between ethanol intake and cognitive decline

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

Abstract This pre-doctoral fellowship (F31) grant application is designed to promote the training of Shelly-Ann Love, a pre-doctoral student in the Department of Epidemiology at the University of North Carolina. Her goal is to become an independent researcher who conducts innovative, translational health research. During the F31 training the applicant will be mentored by her sponsors Drs. Kari North and Gerardo Heiss. The topic of the proposed research is a multidisciplinary assessment of the role of ethanol intake in age-related cognitive decline, as modified by genetic susceptibility. Because of the increasing number of older adults the prevalence of dementia will quadruple from 5.2 million to 16 million by 2050, with an expected increase of healthcare cost from $203 billion to $1.2 trillion. Studies of the association of ethanol intake with cognitive decline and dementia have yielded inconsistent findings, likely attributable to a reliance on a single measurement of ethanol intake, non-standardized definitions of cognitive decline, outdated classifications of dementia, short follow-up times, and or lack of analytic control of confounders and effect measure modifiers. Few studies investigated the effects of ethanol intake in black populations despite the higher prevalence, incidence, and cumulative risk of Alzheimer's dementia in blacks compared to whites. Importantly, no study has investigated the effects of ethanol intake on cognition from mid-life to older adulthood. Further, variation within ethanol- metabolizing genes alters the rate of ethanol oxidation, yet few studies have evaluated effect measure modification of the ethanol intake-cognitive decline relationship by genetic variation in ancestrally diverse populations. Thus, studies based on diverse populations with repeated measurements of ethanol intake and cognitive function that have been genotyped for ethanol-metabolism SNPs are needed to better understand the relationship of ethanol intake with cognitive decline. These aims will be met through the training proposed in this application and the doctoral research based on the bi-racial, population-based Atherosclerosis Risks in Communities (ARIC) cohort of 12,773 black and white adults between the ages of 45-64 years at intake. Analyses will include repeated measurements on participants who attended 5 examinations over 20 years of follow-up. This research responds to a need to identity susceptibility and modifiable behavioral factors that might prevent, or delay the progression of cognitive decline and dementia. The potential impact of the study is its ability to contribute new information on the putative effects of ethanol intake on cognitive decline, and the potential public health risks and benefits of ethanol intake.