Multimodal brain imaging study of 36,678 participants reveals adverse effects of moderate drinking

Abstract

Alcohol consumption can have significant deleterious consequences, including brain atrophy, neuronal loss, poorer white matter fiber integrity, and cognitive decline, but the effects of lightto-moderate alcohol consumption on brain structure remain unclear. Here we examine the associations between alcohol intake and brain structure using structural, diffusion tensor, and neurite orientation dispersion and density imaging data from 19,825 generally healthy middle-aged and older adults from the UK Biobank. Systematically controlling for potential confounds, we found that greater alcohol consumption was associated with lower global gray and white matter volume, regional gray matter volume in cortical and subcortical areas, and white matter fiber integrity and complexity. Post hoc analyses revealed that these associations were non-linear. Our findings extensively characterize the associations between alcohol intake and gray and white matter macrostructure and microstructure. Consuming two or more units of alcohol per day, equivalent to one drink in some establishments, could have negative effects on brain health, an important public health finding.Converging lines of research provide compelling evidence that chronic, excessive alcohol consumption is associated with global brain atrophy and regional brain changes. [1][2][3] Recent meta-analyses of magnetic resonance imaging (MRI) findings show that individuals with alcohol use disorder (AUD) have less global white matter volume (WMV) 4 and less gray matter volume (GMV) -both globally and locally in corticostriatal-limbic regions 5 -than healthy controls.Further, in a meta-analysis of pooled, multinational datasets from 33 imaging sites, individuals with AUD had lower local thickness and surface area of the hippocampus, thalamus, putamen, and amygdala than controls. 6In studies using diffusion-weighted MRI (dMRI), which allows a non-invasive investigation of white matter microstructure via measures of water molecule diffusion, individuals with AUD had lower fractional anisotropy (FA; the directional coherence of water molecule diffusion) and greater mean diffusivity (MD; the magnitude of water molecule diffusion) in the corpus callosum, frontal forceps, internal and external capsules, fornix, superior cingulate, and longitudinal fasciculi than controls. 1,7 However, because conventional dMRI measures (FA and MD) are based on a simplistic model of brain tissue microstructure, they fail to account for the complexities of neurite geometry. 8 For example, the lower FA observed in individuals with AUD 1,7 may reflect lower neurite density and/or greater orientation dispersion of neurites, which conventional dMRI measures do not differentiate. 9,10 A key question raised by prior findings in individuals with AUD that remains is whether, similar to heavy drinking, light-to-moderate alcohol consumption adversely affects brain structure. Further, is the relationship between alcohol intake and brain structure linear? In some studies of middle-aged and older adults, moderate alcoh...

Genetic underpinnings of risky behaviour relate to altered neuroanatomy

“…We excluded participants with putative sex chromosome aneuploidy (N = 6) or a mismatch between genetic and reported sex (N = 10), participants of non-European ancestry (N = 893), and participants who did not pass the UKB quality-control thresholds (N = 14), described in Bycroft et al 27 . To minimize the potential influence of neurotoxic effects due to excessive alcohol intake 21,22 , we also excluded current heavy drinkers (531 females consuming more than 18 drinks per week and 793 males consuming more than 24 drinks per week) 22,23 . To exclude potential former drinkers, we also removed 426 participants who indicated that they did not drink alcohol.…”

“…We first regress our measure of risky behaviour on total (whole-brain) grey matter volume (GMV) while controlling for age, birth year, gender, handedness, height, total intracranial volume and the first 40 genetic principal components, which account for genetic population structure (see Supplementary Methods 1.2). To exclude confounding effects of excessive alcohol consumption 21 , we excluded from the analysis all current or former heavy drinkers (see Methods) 22,23 . We find an inverse association between total GMV and risky behaviour (standardized β = −.122; 95% confidence interval (CI) [−.156, −.087]; t(12,561) = −6.92; P < 4.86 × 10 −12 , two-sided).…”

Human brain anatomy reflects separable genetic and environmental components of socioeconomic status

“…2,427 individuals who were current heavy drinkers, where heavy drinking is defined as consuming more than 24 drinks per week for males and more than 18 drinks per week for females ( 41, 42 ) 1…”

“…Our baseline analyses implicitly adjusted for heavy drinking by excluding heavy drinking individuals. A recent study has shown that even moderate alcohol consumption is associated with reduction in GMV even when educational attainment is adjusted for ( 42 ). Since alcohol drinking behavior is known to be related to SES, it may be hypothesized that the alcohol consumption is a factor that constitutes the observed SES-GMV associations.…”

“…8-mm Full-Width-at-Half-Maximum Gaussian kernel was then used to spatially smooth the pre-processed images. More details can be found in our pre-registered analysis plan (https://osf.io/kg29c/) as well as in the recent publications of BIG BEAR consortium (41,42). the VBM analyses that did not contain any or sufficient grey matter.…”