Greater alcohol intake predicts accelerated brain aging in humans, which mediates the relationship between alcohol intake and behavioral inflexibility

Abstract

Background

Hazardous use of alcohol is associated with cognitive-behavioral impairments and accelerated aging. To date, however, accelerated brain aging has not been tested as a mediating factor between alcohol use and associated task-based behavioral deficits, such as behavioral inflexibility. Here, we evaluated hazardous alcohol use as a predictor of machine learning-derived brain aging and tested if this measure accounted for the relationship between hazardous alcohol use and a task-based measure of behavioral flexibility.

Methods

In this secondary analysis, we applied brainageR, a machine learning algorithm, to anatomical T1-weighted magnetic resonance imaging (MRI) images to estimate brain age for a sample of healthy adults (ages 22–40) who self-reported alcohol use with the alcohol use disorder identification test (AUDIT) and performed the hidden association between images task (HABIT), a behavioral flexibility task. Behavioral inflexibility was quantified as the proportion of perseverative errors performed on the HABIT as a measure of habitual action selection. We then analyzed AUDIT score as a predictor of brain aging, and brain aging as a predictor of behavioral inflexibility. Lastly, we conducted a mediation analysis to evaluate brain aging as a mediator between alcohol use and behavioral inflexibility.

Results

Controlling for chronological age and sex, a higher AUDIT score predicted significantly more accelerated brain aging, which was further associated with more perseverative errors on the HABIT. Moreover, brain aging significantly mediated the association between AUDIT scores and behavioral inflexibility.

Conclusions

Our findings demonstrate that alcohol use is a significant predictor of accelerated brain aging, even in young adulthood. In addition, our findings suggest that such brain changes may mechanistically link more hazardous alcohol use to impaired behavioral flexibility. Future studies should also explore factors, such as other lifestyle behaviors, that may mitigate alcohol- and age-related processes.