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.