Alcohol intake and brain white matter in middle aged men: Microscopic and macroscopic differences

Abstract

Heavy alcohol consumption is associated with deleterious changes in the brain but associations of moderate alcohol intake are not well understood. We examined the association of alcohol consumption with brain white matter health in 377 middle-aged men (56-66 years old; mean 61.8 ± 2.6 years) who were participants in the Vietnam Era Twin Study of Aging (VETSA). T1-, T2-, proton density-, and diffusion-weighted magnetic resonance images were obtained. Diffusion measures were quantified from 12 major white matter tracts. Global white matter lesion (WML) burden was also quantified. Mixed effects linear models examined differences in diffusivity and WMLs by amount of alcohol intake. Analyses adjusted for numerous demographic, health, and lifestyle variables. An inverted-U association was found between alcohol intake and fractional anisotropy (FA) in several tracts, including the inferior-frontal-occipital fasciculus, uncinate fasciculus, superior longitudinal fasciculus, the forceps minor and the anterior thalamic radiations. In these tracts, FA increased with increasing alcohol intake, peaking with moderate alcohol intake (9-28 drinks in 14 days), and declining with heavier intake. Associations remained significant after exclusion of individuals with diabetes or hypertension. There was a U-shaped association in WML burden with highest burden among never drinkers and heavy drinkers (>28 drinks in 14 days). This association was no longer significant after exclusion of individuals with hypertension, since WML burden among heavy drinkers no longer differed from that of other drinkers. This suggests that hypertension related to heavy alcohol intake may contribute to WML burden observed among heavy drinkers. Together, these correlational results suggest that among middle-aged men, moderate drinking may be associated with metrics of better white matter health, particularly microstructural measures, whereas drinking beyond recommended guidelines may be associated with both microstructural and macrostructural white matter damage.

Keywords: Aging; DTI; Diffusion-weighted imaging; Ethanol; Fractional anisotropy; Neuroimaging; White matter hyperintensity; White matter lesion.

Fig. 1

Fractional Anisotropy (FA) as a function of alcohol intake group for 12 white matter tracts. Estimated means are adjusted for scanner and age. Error bars indicate standard error of the mean. In fully adjusted models, FA differed significantly by alcohol group for the UF, IFOF, ATR, SLF, and Fmin. Significant post-hoc comparisons, after adjustment for multiple comparisons, are shown. UF = uncinate fasciculus; IFOF = inferior fronto-occipital fasciculus; ATR = anterior thalamic radiations; SLF = superior longitudinal fasciculus; ILF – inferior longitudinal fasciculus; Fmin = forceps minor; Fmaj = forceps major; CC – corpus callosum; FX = fornix, CgH = cingulum, parahippocampus; CgC = cingulum, cingulate; CST = corticospinal tract. *p < 0.05; **p < 0.01; ***p < 0.001.

Fig. 2

Radial diffusivity (RD) as a function of alcohol intake group for the five tracts that showed significant FA differences. Estimated means are adjusted for scanner and age. Error bars show standard error of the mean. Significant differences in RD were found for the IFOF and Fmin. Significant posthoc comparisons, after correction for multiple comparisons, are shown. For abbreviations, see legend for Fig. 1. *p < 0.05; **p < 0.01.

Fig. 3

White matter lesion (WML) burden as a function of alcohol intake group. WMLs were calculated as the proportion of log abnormal white matter volume to log total white matter volume. Estimated means from the base model, which adjusted for scanner and age, are shown. Error bars indicate the standard error of the mean.