Critique 145: Alcohol consumption and brain structure on MRI scans — 25 August 2014

Gu Y, Scarmeas N, Eaton Short E, Luchsinger JA, DeCarli C, Stern Y, Manly JJ, Schupf N, Mayeux R, Brickman AM.  Alcohol intake and brain structure in a multiethnic elderly cohort.  Clinical Nutrition 2014;33:662e667. 

Authors’ Abstract

Background & aims:  Evidence suggests that consuming light-to-moderate amounts of alcohol reduces the risk of dementia and is associated better cognitive function and less cardiovascular disease, relative to those consuming no or heavy alcohol.  There are only minimal data on the association between alcohol and brain magnetic resonance imaging (MRI) markers.  This study aimed to examine the association between alcohol and brain structure measured with MRI.

Methods: In this cross-sectional study, high-resolution structural MRI was collected on 589 multi-ethnic community residents of New York aged ≥ 65 with available alcohol intake assessments via a food frequency questionnaire.  Total brain volume (TBV), white matter hyperintensity volume (WMHV), and presence of infarcts were derived from MRI scans with established methods. We examined the association of alcohol intake with these imaging markers using regression models adjusted for demographic, clinical, and vascular risk factors.

Results: Compared to non-drinking, light-to-moderate total alcohol (b = 0.007, p = 0.04) or wine (b = 0.008, p = 0.05) intake, but not beer or liquor intake, was associated with larger TBV.  Further analysis showed a dose-response association between alcohol (p-trend = 0.03) or wine (p- trend = 0.006) and TBV.  Overall, alcohol intake was not associated with WMHV or brain infarcts.  

Conclusions:  Our study suggests that among older adults in the community, light-to-moderate alcohol intake, in particular wine, is associated with larger TBV.  These findings suggest that light to moderate alcohol consumption is potentially beneficial for brain aging, but replication is needed.

Forum Comments

While many epidemiologic studies have suggested that light-to-moderate drinkers have a lower risk of developing Alzheimer’s Disease or other types of dementia, limited data are available relating alcohol intake to measurements of brain size and structure.  Anstey et al (2006) reported: “In men, weekly alcohol consumption had a positive linear association with ventricular volume and gray matter and a negative linear association with white matter. In women, weekly alcohol consumption had a nonlinear relationship with cerebrospinal fluid and white matter. Alcohol consumption was not associated with white matter hyperintensities, corpus callosum size, hippocampal or amygdala volumes in analyses adjusting for confounding variables.” 

A number of other studies (e.g., de Bruin et al, den Heijer et al) have shown that at least some groups of subjects have favorable effects on brain structure associated with alcohol consumption.  In contrast, others reports  (e.g., Mukamal et al, Fukuda et al) showed that alcohol intake was inversely associated with indices of brain structure.   However, in terms of net effects of alcohol on the risk of clinical dementia, many studies show a protective effect.  For example, from the long-term follow up of a population-based cohort in Australia, the Dubbo Study, Simons et al found that alcohol consumption and regular exercise (including gardening and daily walking) were the two lifestyle habits that were most strongly associated with a lower risk of developing dementia.

The present study was based on a large population-based, multi-ethnic population in New York City.  A brain MRI was obtained when subjects were an average of 80.1 years of age.   Alcohol intake was assessed, at the time of the brain MRI, by a food-frequency questionnaire that was administered twice 2 months apart (and showed no significant differences between the two administrations).  A total of 180 (31%) of subjects reported light-to-moderate alcohol intake; 409 reported no alcohol intake.  Overall, 14% reported beer intake, 21% wine intake, and 13% liquor intake. 

In multivariable analyses, potential confounders or modifiers of effect included age, sex, education, caloric intake and BMI, and a history of diabetes, hypertension, heart disease, or clinical stroke.  Subjects were also categorized by ApoE genotype, smoking status, and race; supplemental analyses were done among subject reporting no alcohol intake to exclude subjects with a history of previous alcohol intake and previous heavy drinking.  Because of few heavy drinkers in this cohort, comparisons were done only between non-drinkers and “light-to-moderate” drinkers (>0 – ≤ 30 drinks/month for women and >0 – ≤ 60 drinks/month for men).   

Key results showed that subjects reporting a total alcohol intake in the light-to-moderate range had larger total brain volumes (i.e., less brain atrophy) than non-drinkers in the basic adjusted analyses (p=0.05), but this was attenuated when the subject gave a previous history of heart disease,  hypertension, or diabetes, and when adjusted for BMI.  There was a significant trend (p=0.03) indicating that increase in total alcohol consumption was associated with increase in brain volume; when type of beverage was considered, only wine consumption was associated with increased brain volume.  Alcohol intake did not relate to white matter hyperintensity volume or the presence of brain infarcts.    

Specific comments on paper by Forum members:  Reviewer Ellison commented that this is not a very large study, and the differences in brain size and structure according to alcohol intake were not large.  Further, it is based on a cross-sectional analysis, so it is possible that people with larger brains to begin with were more likely to consume wine or total alcohol (rather than their alcohol intake increasing their brain size). 

Reviewer Waterhouse pointed out that the only assessment of alcohol intake was “over the past year,” at the time of the MRI.  “I would presume that differences in brain volume might take time to evolve, so that the current snapshot might not be the best assessment of the relevant alcohol exposure, if there was to be any relationship.   I agree that any association is weak at best for increasing brain volume, but this also means that there would be a weak association with any effect on brain volume.”

Forum member Skovenborg comments:  “As a cross-sectional study the link between association and causation is weak, and there are indications of residual confounding in the present study, e.g., the diet of wine drinkers vs beer and spirits drinkers.  Anyway the association of moderate alcohol intake with larger brain volumes in elderly people is reassuring.”

Should the elderly be encouraged or discouraged to consume some alcohol?  Reviewer Keil listed some reasons why instructing the elderly to refrain from light-to-moderate amounts of alcohol may not be wise: “First, with increasing age the relative risk of a risk factor or a protective factor may diminish, because the risk factor age is overwhelming other risk factors, but the absolute risk is increasing; this means that an intervention may have a greater impact in older people as compared with younger people.  Even for an important risk factor such as hypertension, with increasing age the relative risk of hypertension for CVD or all-cause mortality declines, but the absolute risk increases.”  In addition, Keil notes that “We have overwhelming epidemiologic data showing that in people above age 55, alcohol has clear beneficial effects.  The explanation is easy: In younger people with a low risk of dying from cardiovascular disease (CVD), light to moderate amounts of alcohol cannot protect against a risk which hardly exists, while in elderly and older people CVD risk increases exponentially, and in those people small to moderate amounts of alcohol can exert their beneficial effect. The overall net result is overwhelmingly positive in favour of alcohol consumption.”

Reviewer Finkel noted: “I have long believed that too much concern is expressed about the susceptibility of the elderly to drinking, particularly to moderate drinking.  In fact, it has appeared to me that the elderly both tolerate and may preferentially benefit from moderate drinking.  Maybe we are seeing in this study part of the reason.”  Finkel added: “The very wise Michel de Montaigne wrote, ‘ . . . drinking is the almost last pleasure that the years steal from us.’”  

Given the inconsistences in previous reports on the effects of alcohol on brain size, we must conclude that this study suggests that there might be a weak positive association between alcohol (especially wine intake) and brain size, but an association is not definitive.  An inverse relation between moderate drinking and clinical evidence of dementia has received support from a large number of epidemiologic studies and may be a better association for us to use when advising the public regarding alcohol consumption.     

References from Forum review

Anstey KJ, Jorm AF, Reglade-Meslin C, Maller J, Kumar R, von Sanden C, et al.  Weekly alcohol consumption, brain atrophy, and white matter hyperintensities in a community-based sample aged 60 to 64 years. Psychosom Med 2006;68:778e85.

de Bruin EA, Hulshoff Pol HE, Schnack HG, Janssen J, Bijl S, Evans AC, et al. Focal brain matter differences associated with lifetime alcohol intake and visual attention in male but not in female non-alcohol-dependent drinkers. Neuroimage 2005;26:536e45.

den Heijer T, Vermeer SE, van Dijk EJ, Prins ND, Koudstaal PJ, van Duijn CM, et al.  Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia. Am J Clin Nutr 2004;80:992e7.

Fukuda K, Yuzuriha T, Kinukawa N, Murakawa R, Takashima Y, Uchino A, et al.  Alcohol intake and quantitative MRI findings among community dwelling Japanese subjects. J Neurol Sci 2009;278:30e4.

Mukamal KJ, Longstreth Jr WT, Mittleman MA, Crum RM, Siscovick DS.  Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study. Stroke 2001;32:1939e 46.

Simons LA, Simons J, McCallum J, Friedlander Y.  Lifestyle factors and risk of dementia: Dubbo Study of the elderly.  Med J Aust 2006;184:68-70.

Forum Summary

While numerous prospective epidemiologic studies have provided evidence that light-to-moderate amounts of alcohol reduce the risk of dementia and heavy drinking increases the risk, there are few studies on the effects of alcohol on brain structure assessed by magnetic resonance imaging (MRI).  The present study is a cross-sectional evaluation between reported alcohol intake and MRI-assessed brain structure among 589 multi-ethnic community residents of New York. Total brain volume (TBV), white matter hyperintensity volume (WMHV), and presence of infarcts were derived from MRI scans when subjects were, on average, 80 years of age..

A key finding of this analysis is that, in comparison with non-drinkers, light-to-moderate alcohol intake (up to an average of 1 drink/day for women or 2 drinks/day for men, which was reported in 31% of their subjects) was associated with larger TBV (i.e., less brain atrophy).  The effect was primarily among consumers of wine rather than of beer or liquor.  Significant associations were not found for alcohol or for specific beverages for other measures of brain structure (WMHV or presence of infarcts).   

Forum reviewers considered this to be an appropriate analysis that was able to consider many of the potential confounders of such an association.  On the other hand, it was not a large study and was based on a cross-sectional analysis; thus it cannot be used to judge causation (e.g., it is possible that people with larger brains to begin with were more likely to consume wine or total alcohol, rather than their alcohol intake increasing their brain size).    

Data from many previous studies have shown that moderate alcohol intake lowers the risk of developing clinical signs of cognitive decline and of dementia.  Such a finding has led Forum members to be of the opinion that instructing the elderly to refrain from light-to-moderate amounts of alcohol may not be wise.  Although prospective studies may show that the decrease in the risk ratio for dementia (comparing drinking with abstainers) tends to be less among the elderly than among middle-aged subjects, the absolute risk of dementia increases markedly with age.  Thus, any intervention that lowers the risk of cognitive impairment will have a much greater impact in older people as compared with younger people. 

Given the inconsistences in previous reports on the effects of alcohol on brain structure, we must conclude that while this study suggests that there might be a beneficial association between alcohol (especially wine intake) and brain size, such a relation is not definitive.  An inverse relation between moderate drinking and clinical evidence of dementia, however, has received support from a large number of prospective epidemiologic studies; it may be a better association for us to use when advising the elderly regarding alcohol consumption.   

Overall, scientific data indicate that, for elderly subjects without contraindications to alcohol, small amounts of wine or other alcoholic beverage consumed regularly may reduce the risk of dementia and other diseases of ageing.  As stated by Michel de Montaigne many centuries ago: “ . . . drinking is the almost last pleasure that the years steal from us.”      

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Contributions to this critique by members of the International Scientific Forum on Alcohol Research were provided by the following members:

Ulrich Keil, MD, PhD, Institute of Epidemiology and Social Medicine,  University of Münster, Münster, Germany

Creina Stockley, PhD, MBA, Clinical Pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark

Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis; Davis, CA, USA

Dag S. Thelle, MD, PhD, Senior Professor of Cardiovascular Epidemiology and Prevention, University of Gothenburg, Sweden; Senior Professor of Quantitative Medicine at the University of Oslo, Norway

David Vauzour, PhD, Senior Research Associate, Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA