Moderate alcohol consumption was linked to higher brain iron and worse cognitive function, an observational study showed.
Among nearly 21,000 people in the U.K. Biobank cohort, alcohol intake above 7 weekly units (56 g, or about four standard drinks per week in the U.S.) was associated with markers of higher brain iron in multiple basal ganglia regions, according to Anya Topiwala, PhD, of the University of Oxford in England, and co-authors.
Markers of higher brain iron were in turn associated with poorer scores on tests of executive function, fluid intelligence, and reaction speed, Topiwala and colleagues reported in PLoS Medicine.
“This is the first study, to our knowledge, demonstrating higher brain iron in moderate drinkers,” Topiwala told MedPage Today. “The findings offer a potential pathway through which alcohol can cause cognitive decline.”
“Establishing the pathway is important as it may offer clues as to ways we can intervene to reduce the harm,” Topiwala said. “For iron, we actually have medicines — iron chelators — that could reduce levels.”
The analyses suggest that changes in iron accumulation may contribute to the adverse effects on brain structure and cognitive performance seen in people who consume alcohol in moderate or greater amounts, commented Henry Kranzler, MD, of the University of Pennsylvania in Philadelphia, who wasn’t involved with the research.
“The findings, though, are largely limited to the basal ganglia, collections of brain cells that are involved in motor control, executive functions, and emotions,” Kranzler told MedPage Today.
Other recent research from the U.K. Biobank cohort reported links between one or two drinks a day and reduced overall brain volume on MRI.
“Whereas prior findings in a large neuroimaging study showed that the effects of moderate or greater drinking on gray and white matter volume were widespread in the brain, other causal mechanisms are likely to be involved in alcohol’s adverse effects on brain,” Kranzler noted. “Further research in this area could help identify these.”
Mechanisms by which alcohol could influence brain iron and whether there are clinical consequences of subtle elevations in brain iron are unknown, Topiwala and co-authors acknowledged.
Nonetheless, the findings add to growing evidence that even moderate alcohol consumption may adversely affect brain health, noted Howard Fillit, MD, of the Alzheimer’s Drug Discovery Foundation in New York City, who wasn’t involved with the study.
“We now have evidence showing lifestyle interventions can reduce the risk of developing dementia, and reduction in alcohol consumption may be one of the ways people can potentially lower their risk for dementia, along with other lifestyle modifications in areas like diet and exercise,” Fillit said.
To explore relationships between alcohol consumption and brain iron, Topiwala and co-authors studied the U.K. Biobank cohort of over half a million people. They identified 20,965 participants who underwent brain MRIs, of whom 6,936 had liver imaging as well for the assessment of systemic iron.
The brain imaging group averaged 55 years of age and 48.6% were women. Overall, 2.7% of this cohort said they were non-drinkers.
Alcohol intake was self-reported at baseline. Overall, mean alcohol intake was 17.7 units per week.
The researchers evaluated cognition when participants underwent imaging and again at a mean 5.82 years after baseline. Executive function was assessed with the trail-making test, fluid intelligence was evaluated with puzzle tasks, and reaction time was gauged by a task based on the “Snap” card game.
In people consuming 7 weekly units of alcohol or more, greater alcohol consumption was associated with significantly higher iron in the putamen, caudate, and substantia nigra, but lower iron in the thalami.
Elevated liver iron was seen at 11 units (88 g, or just over six standard U.S. drinks) of alcohol weekly or more.
Systemic iron levels partially mediated associations of alcohol intake with brain iron. Mendelian randomization analyses using genetic variants as proxies for weekly alcohol consumption supported observational findings.
Study limitations included the fact that myelin may alter imaging markers, the researchers acknowledged. In addition, alcohol use was self-reported.
Researchers were supported by the Wellcome Trust, China Scholarship, UK Medical Research Council, European Commission, NIHR Oxford Biomedical Research Centre, BHF Centre of Research Excellence, U.S. Department of Veterans Affairs, Sir Henry Dale Fellowship, British Heart Foundation, NIHR Cambridge Biomedical, Li Ka Shing Centre for Health Information and Discovery, and the NIH.
Topiwala had no relevant disclosures.
Study coauthors reported relationships with Axcella Therapeutics, Perspectum Ltd., and PLoS Medicine’s statistical board.