Associations between alcohol consumption and gray and white matter volumes in the UK Biobank

Abstract

Heavy alcohol consumption has been associated with brain atrophy, neuronal loss, and poorer white matter fiber integrity. However, there is conflicting evidence on whether light-to-moderate alcohol consumption shows similar negative associations with brain structure. To address this, we examine the associations between alcohol intake and brain structure using multimodal imaging data from 36,678 generally healthy middle-aged and older adults from the UK Biobank, controlling for numerous potential confounds. Consistent with prior literature, we find negative associations between alcohol intake and brain macrostructure and microstructure. Specifically, alcohol intake is negatively associated with global brain volume measures, regional gray matter volumes, and white matter microstructure. Here, we show that the negative associations between alcohol intake and brain macrostructure and microstructure are already apparent in individuals consuming an average of only one to two daily alcohol units, and become stronger as alcohol intake increases.

Fig. 1. Empirical distributions of variables.

SD standard deviation, GMV gray matter volume, WMV white matter volume.

Fig. 2. Scatter plots of whole-brain standardized gray matter volume (females, upper left; males, upper right) and standardized white matter volume (females, lower left; males, lower right), all normalized for head size, against the individual’s age (x-axis).

The plots also show the LOWESS regression line (smoothness: a = 0.2). The 95% confidence interval is indistinguishable from the regression line. The colors are representative of the average daily alcohol consumption.

Fig. 3. Scatter plots of whole-brain standardized gray matter volume (females, upper left; males, upper right) and standardized white matter volume (females, lower left; males, lower right), all normalized for head size, against the individual’s daily alcohol consumption (x-axis, in log scale).

The plots also show the LOWESS regression line (smoothness: a = 0.2), with its 95% confidence interval. The dashed line represents the average standardized volume of the full sample (males and females).

Fig. 4. Bar plots representing the average residual volume of whole-brain gray and white matter volume for individuals grouped by the number of daily alcohol units after controlling for standard control variables.

The mean residuals are in terms of standard deviations of the dependent variable, where zero represents the average residual in the full sample. The error bars represent the 95% confidence interval. *p < 0.01 and **p < .0001 for groups showing a significant difference against the group consuming up to one alcohol unit daily. Supplementary Figure 1 replicates this Figure following the exclusion of individuals who consume a high level of alcohol (i.e., females who report consuming more than 18 units/week and males who report consuming more than 24 units/week).

Fig. 5. Associations between daily alcohol units and white matter microstructure indices of interest across white matter tract regions.

Asterisks denote statistically significant effects, p < 1.64 × 10⁻⁴. Colors represent the expected change in each imaging derived phenotype resulting from the increase in daily consumption from 1 to 2 units, based on the regression model. FA fractional anisotropy, ICVF intracellular volume fraction, ISOVF isotropic volume fraction, MD mean diffusivity, OD orientation dispersion, r right, l left.