No safe level of alcohol consumption for brain health: observational cohort study of 25,378 UK Biobank participants

Abstract

Objectives To estimate the relationship between moderate alcohol consumption and brain health, determining the threshold intake for harm and identifying whether population subgroups are at differential risk. Design Observational cohort study. Alcohol consumption was determined at baseline assessment visit using touchscreen questionnaire (2016-10). Multi-modal MRI brain and cognitive testing were performed subsequently (2014-20). Clinical data was extracted from linked Hospital Episode Statistics. Setting UK Biobank study. Brain imaging was performed on identical scanners with identical protocols at three UK centres (2014-20). Participants 25,378 participants (mean age 54.9, s.d.=7.4 years). Main outcome measures Brain health as defined by structural and functional MRI brain measures. Results Alcohol consumption was negatively linearly associated with global brain grey matter volume (beta= -0.1, 95%CI= -0.11 to -0.09, p<2x10-16). The association with alcohol was stronger than other modifiable factor tested and robust to unobserved confounding. Widespread negative associations were observed with white matter microstructure (beta= -0.08, 95%CI= -0.09 to -0.06, p<2x10-16) and positive correlations with functional connectivity. Higher blood pressure and body mass index increased risk of alcohol-related harm (SBP*alcohol: beta= -0.01, 95%CI = -0.02 to -0.004, p=0.005; BMI*alcohol: beta= -0.01, 95%CI = -0.02 to -0.002, p=0.02). Binging on alcohol had additive negative effects on brain structure on top of the absolute volume consumed (daily compared to never binging: beta= -0.19, 95%CI= -0.30 to -0.08, p<0.01). No evidence was found for differential effects of drinking wine, beer or spirits. Conclusions No safe dose of alcohol for the brain was found. Moderate consumption is associated with more widespread adverse effects on the brain than previously recognised. Individuals who binge drink or with high blood pressure and BMI may be more susceptible. Detrimental effects of drinking appear to be greater than other modifiable factors. Current low risk drinking guidelines should be revisited to take account of brain effects.

Alcohol and the Brain

“…It has been suggested a similar J-or U-shaped relationship exists with brain structure, but only a few MRI studies have found support for this assumption [41][42][43]. More recent large-scale studies of the general population have in fact shown negative linear associations between alcohol consumption and brain structure, showing widespread reductions in grey and white matter volume as well as white matter microstructure and cortical thickness [44][45][46][47]. Taken together, these studies highlight that there is no protective effect of light drinking (e.g., 1-<7 drinks per week) over abstinence and in fact show, similar to alcohol dependence though to a lesser degree, that any level of alcohol consumption can affect brain volume and white matter microstructure.…”

“…It should be noted that these are cross-sectional association studies, and it is not possible to infer causality or estimate the impact of alcohol on the brain over time. Furthermore, only a small proportion of the variance in brain structure is explained by alcohol consumption [44,46]. A study on brain age further found that only those who drank daily or almost daily showed a difference between chronological and predicted brain age, and there were no differences in those who drank less frequently or abstained from alcohol [48].…”

“…This suggests that whilst low levels of alcohol consumption may affect brain structure, this may not negatively impact healthy brain aging. An important caveat to the generalizability is the relatively small amount of large-scale imaging datasets and the findings discussed here primarily relate to the UK BioBank dataset [44,[46][47][48].…”

“…Chronic alcohol consumption can therefore cause the de-regulation of microglial activation. This in turn can lead to degeneration of brain tissue and is likely associated with brain volume loss [46], as covered in Section 1.…”

“…Resting state functional connectivity (RSFC) is a technique that quantifies connections between brain regions based on temporal correlation of BOLD signal change. In a recent UK BioBank study of 25,378 individuals, increased within-network connectivity was identified within the default mode network (DMN) in those with higher alcohol consumption [46]. The DMN is believed to be involved in the processing of self-awareness, negative emotions, and rumination, so increased connectivity within this network may infer a decreased responsiveness to external incentives and increased rumination towards alcohol-related cues [118].…”