The relationship between alcohol use disorder, measures of cognitive decline, and Alzheimer disease biomarkers in middle aged and older adults

BACKGROUND: Alcohol use disorder (AUD) is associated with increased risks of some neuropsychiatric conditions and early-onset dementia. However, the association between Alzheimer disease (AD) and AUD is poorly characterized. To address this, we studied associations between AUD, cognition, and measures of AD neuropathology. METHODS: We measured a lifetime history of AUD, cognitive decline, and blood biomarkers for AD in middle-aged and older participants (47-87 years) from the St. Louis site of the Collaborative Study on the Genetics of Alcoholism (COGA) (N = 392). Cognitive decline was measured using the Eight-item Informant Interview to Differentiate Aging and Dementia (AD8) (N = 366); 154 individuals had AD biomarkers derived from plasma measurements (Amyloid Probability Score 2, Aβ42/Aβ40, and %p-tau217). We used Poisson regression models to evaluate the relationship between AUD, age, and cognitive decline. AUD was categorized as no AUD, mild AUD, or moderate-to-severe AUD, and age was modeled as a piecewise linear variable segmented by decade. Linear regressions were used to assess the association between AD blood biomarkers and AUD. RESULTS: Analyses revealed a significant association between moderate-to-severe AUD and increased cognitive decline in middle-aged and older adults (RR = 1.4, p < 0.001). While a greater proportion of participants with moderate-to-severe AUD met the Aβ42/Aβ40 threshold for predicting elevated brain amyloid compared to those with mild or no AUD, consistent with our hypothesis, this trend did not achieve statistical significance. CONCLUSIONS: These results underscore the importance of addressing AUD as a potentially modifiable risk factor for cognitive decline in middle aged and older adults. Further study is needed to understand the link between AUD and AD biomarkers.