Soojin Lee1, Ahmed Gouda1, Rodrigo Solis Pompa,, Nasrin Akbari1, Saurabh Garg1,2, Thanh-Duc Nguyen1, Madhurima Datta1, Saqib Basar1, Yosef Chodakiewitz2, Somayeh Meysami3,4 Daniel J. Durand2,,, Sam Hashemi1,2, Cyrus A. Raji5,6,
1: Vigilance Health Imaging Network, Vancouver, Canada
2:Prenuvo Inc
3: Pacific Brain Health Center, Pacific Neuroscience Institute and Foundation, Santa Monica, CA, USA
4: Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA, USA
5: Washington University School of Medicine in St Louis, Mallinckrodt Institute of Radiology, St. Louis, MO, USA
6: Department of Neurology, Washington University in St. Louis, MO, USA
Synopsis
- Motivation: Current research on alcohol's impact on brain structure mainly focuses on individuals with alcohol use disorder (AUD), leaving effects on non-AUD drinkers underexplored. Moreover, no studies have simultaneously examined both brain and organ volume changes via MRI.
- Goal(s): To determine if moderate to high alcohol intake is linked to structural changes in brain and whole-body metrics among non-AUD individuals.
- Approach: We analyzed 1,134 MRI scans, comparing metrics in matched pairs of abstainers and drinkers, using segmentation models for body and brain volume assessment.
- Results: Alcohol consumption group exhibited larger liver and kidney, higher visceral fat, and greater brain atrophy than abstainers, with significant cross-organ associations.
Impact
This study uniquely links alcohol consumption with structural changes in both brain and body organs among non-AUD individuals. These findings prompt further investigation into alcohol’s broader health implications, particularly concerning cross-organ relationships and their clinical significance.
Introduction (126)
Alcohol consumption significantly contributes to global health burden and ranks as a primary risk factor for many adverse health outcomes1. Chronic alcohol use is associated with numerous detrimental effects, including elevated cancer risk, cardiovascular diseases, and accelerated biological aging2,3,4. While substantial research has investigated alcohol’s impact on brain structure, most studies focus on individuals with alcohol use disorder (AUD, defined by impaired control and negative impact on life)5. Research on brain structure among individuals who consume alcohol without AUD is limited, often due to methodological challenges such as small sample sizes and inadequate control of confounders. To address these gaps, our study rigorously controls for confounders while examining alcohol-related changes in whole-body and brain metrics from MRI scans, providing a comprehensive view of alcohol’s systemic impact.
Methods (224)
We analyzed 1.5T whole-body MRI scans from 1,134 participants across the U.S. and Canada using 3D nnU-Net segmentation models. Brain MRI scans (1.5T) were processed with Fastsurfer. Whole-body metrics included: 1) organ volumes (lung, liver, spleen, stomach, kidney, and bladder) derived from segmentation, and 2) mass percentages for visceral fat, subcutaneous fat, and total skeletal muscle, calculated from segmentation volumes and normalizing by weight. Brain metrics included global brain volume, subcortical gray matter volume, and the volumes of 95 subcortical and cortical ROIs, normalized by intracranial volume.
Alcohol intake reported via self-questionnaires was converted to average drinks per day. The 1,134 participants comprised 567 pairs matched for age, sex, height, BMI, type 2 diabetes, hypertension, smoking status, and weekly exercise amount, differing only in alcohol intake (Fig. 1). Screening excluded individuals meeting AUD criteria. Those abstaining from alcohol were classified as the Abstainers group, while participants consuming moderate to high levels (≥2 drinks per day) formed the Alcohol Consumption group. The two groups were compared using two-sample t-tests with false discovery rate correction.
For metrics showing significant group differences, we conducted multiple linear regression analyses to assess associations with daily alcohol intake, controlling for age, sex, height, BMI, type 2 diabetes, hypertension, and smoking status. Additionally, we examined relationships between significant whole-body and brain metrics using multiple linear regression, controlling for the same confounders.
Results (198)
For whole-body metrics, the Alcohol Consumption group showed a 10% larger liver volume (p < 0.001), a 5.7% larger kidney volume (p < 0.001), and a 15.6% increase in visceral fat percentage (p < 0.001) compared to the Abstainers group (Fig. 2), with these differences consistently observed across age groups. In the brain, significant volume differences were found in 24 ROIs, with the Alcohol Consumption group showing notably lower volumes than the Abstainers group (Fig. 3). The most pronounced reductions were observed in the right hippocampus, bilateral superior frontal cortex, left medial orbital frontal cortex, left precentral cortex, right supramarginal cortex, total subcortical grey matter, and total brain volume (Fig. 3).
Regression analyses indicated that increased daily alcohol intake was positively associated with larger liver and kidney volumes (p < 0.001) and higher visceral fat levels (p < 0.001) (Fig. 4). Similarly, increased daily alcohol intake was significantly related to greater atrophy in brain regions including the left superior frontal cortex and right hippocampus where significant group differences were observed.
Finally, cross-organ analyses revealed significant associations between the enlarged liver and kidney volumes and brain atrophy in specific ROIs, independent of confounding variables (Fig. 5). No significant relationship was found for visceral fat.
Discussion (128)
Our study reveals that moderate to high alcohol intake, even among individuals without AUD, is linked to measurable increases in liver and kidney volumes, visceral fat, and brain atrophy. The link between alcohol consumption and reductions in brain regions critical for memory, decision-making, and motor function highlights alcohol's neurotoxic effects6, even at moderate levels. This supports the idea that regular intake contributes to accelerated neural aging7,8, with potential long-term cognitive health implications7,8. Additionally, our analyses showed that increased liver and kidney volumes were independently linked to brain atrophy, suggesting systemic effects of alcohol beyond individual organs, possibly through inflammation or metabolic disruptions9,10. Finally, by matching participants for confounders and using advanced MRI segmentation, our approach overcomes limitations in previous research, offering more reliable insights into alcohol’s structural effects.
Conclusion (70)
Moderate to high alcohol consumption is associated with significant structural changes in both whole-body and brain metrics, even in non-AUD individuals. The observed brain atrophy and organ enlargement highlight potential cognitive and physical health risks. Future longitudinal studies are needed to assess the progression and possible reversibility of these structural changes with reduced alcohol intake, as well as to explore age-related vulnerabilities and individual variability in alcohol’s effects on health.
Acknowledgements
We appreciate the support and collaboration of the MRI Technologists, Backend, and Patient Care teams at Prenuvo in the patient care and data acquisition process.
References
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Fig. 1. Participant characteristics in Abstainers and Alcohol Consumption groups. Values are reported as mean (standard deviation) except for count (n).
Fig. 2. Comparison of whole-body metrics between Abstainers and Alcohol Consumption groups. (A) The Alcohol Consumption group exhibits significantly larger liver and kidney volumes and a higher visceral fat (vfat) mass percentage compared to the Abstainers group (***: p < 0.001, FDR corrected). (B) These group differences in liver volume and visceral fat percentage remain consistent across various age groups.
Fig. 3. Comparison of brain metrics between Abstainers and Alcohol Consumption groups. (A) t-statistic maps of cortical and subcortical regions of interest (ROIs) highlight significant volume differences between groups (p < 0.05, FDR corrected). Negative t-values indicate lower volumes in the Alcohol Consumption group. (B) Top 10 ROIs with significant volume differences between groups. Values represent the group mean ROI volumes normalized by intracranial volume and multiplied by 103. pfdr denotes FDR-corrected p-values.
Fig. 4. Associations between daily alcohol intake and significant whole-body and brain metrics (A) Increased daily alcohol intake is associated with larger liver and kidney volumes and higher visceral fat. (B) Higher daily alcohol intake correlates with atrophy in the top 10 ROIs listed in Fig. 3B. Data for the three most strongly correlated brain regions are shown.
Fig. 5. Cross-organ relationships examined via (A) Pearson correlation and (B) regression analyses, adjusted for confounders (age, sex, height, BMI, type 2 diabetes, hypertension, and smoking status). Significant relationships (p < 0.05) are indicated by color. Larger liver and kidney volumes are significantly associated with brain atrophy in specific ROIs, independent of confounding factors
