Background Alcohol use disorder (AUD) is associated with increased risks of neuropsychiatric conditions and 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 (Amyloid Positivity Score 2, Aβ42/Aβ40 and p-tau217/np-tau217 ratio) in older participants from the St. Louis site of the Collaborative Study on the Genetics of Alcoholism (COGA). AUD was defined as having four or more DSM-5 AUD symptoms at the time of heaviest lifetime consumption, as most AUD related morbidity and mortality are associated with moderate/severe AUD. Cognitive decline was measured using the AD8 score (N=356), and AD biomarkers were derived from plasma measurements (N=138). We used Poisson regression models to evaluate the relationship between AUD, age, and cognitive decline, with age modeled as a piecewise linear variable by decade. Linear regressions were used to assess the association between AD blood biomarkers and AUD.

Results Analyses revealed a significant association between AUD and increased cognitive decline in older adults (RR=1.31, p<0.001). No statistical association was seen between plasma AD biomarkers and AUD.

Conclusions These results underscore the importance of addressing AUD as a potentially modifiable risk factor for cognitive decline in older adults. Further study is needed to understand the link between AUD and AD biomarkers.

Washington University has equity ownership interest in C2N Diagnostics and receives royalty income based on technology (stable isotope labeling kinetics and blood plasma assay) licensed by Washington University to C2N Diagnostics. The authors otherwise have no competing interests to disclose.

This study was funded by NIH grants R01 AG065234, R01 AG084723, and P01 AG026276 from the National Institute on Aging (NIA), and R01 AA029308 and U10 AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The authors and their institution received support from these agencies for study design, data collection, statistical analysis, and manuscript preparation. Additional support was provided by the Washington University Institute of Clinical and Translational Sciences through grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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