Project Summary This is a study to investigate the relationship between trajectories of alcohol use, longitudinal changes in brain function, and the development of Alzheimer disease (AD). To address gaps in knowledge about the relationship between alcohol use and AD, we will integrate plasma Aβ testing and a measurement of clinical dementia into ongoing assessments of N=600 participants (age ≥ 50, 17% African American) in a large ongoing study of alcohol use disorder. We will leverage sample collection from the St. Louis site of the Collaborative Study on the Genetics of Alcoholism (COGA), a longitudinal, family-based study of alcohol use disorder funded by NIAAA for over 30 years, with extensive clinical, neuropsychological, electrophysiological, and genetic data from families densely affected by alcohol use disorder and community-based comparison families. The ongoing assessments of older COGA participants includes a comprehensive evaluation of alcohol use, neurophysiological measures including resting-state electroencephalogram (EEG) and event-related brain potentials (ERPs) acquired during cognitive tasks (same as in previous longitudinal assessments), and neuropsychological surveys. Together with existing COGA data, the new combined assessment will allow for creation of powerful measures of alcohol use, brain function, and neuropathology. This represents the first study to integrate AD biomarkers with comprehensive, longitudinal assessments of alcohol use. Aim 1 will examine the effect of alcohol consumption on preclinical AD and longitudinal changes in brain function and cognition in older adults. Aim 2 will investigate genetic, comorbid, environmental, and demographic factors as moderating the effect of alcohol consumption on AD biomarkers and brain function. The innovations include integration of state-of-the-art AD assessment, plasma biomarker of AD, brain function measures of neural synchronicity and connectivity, and comprehensive longitudinal assessment of alcohol use in a high-risk sample that has been followed over 20 years. This proposal is significant because the products and results will apply broadly to our understanding of both the development of AD and the long-term impact of alcohol on the brain.

Relevance to Public Health This project will recruit adults age 50 and older from an existing long-term study of alcohol use disorder to examine the relationship between alcohol use, aging brain function, and Alzheimer disease. This may help researchers develop treatments and ultimately reduce illness and mortality.