An explanation for the negative impact of alcohol on the brain?

Iron accumulation in the brain as a result of drinking alcohol may explain why even moderate consumption is linked to impaired cognitive function.

Results from a large observational study suggest that iron accumulation in the brain is a “plausible pathway” through which alcohol negatively affects cognition, he told Medscape the doctor Dr. Anya Topiwala, Ph.D., senior clinical researcher at the Nuffield Department of Population Health gives University of Oxfordin England.

Study participants who drank 56 grams of alcohol per week had higher levels of brain iron. The UK guideline for ‘low risk’ alcohol consumption is less than 14 units per week, or 112 grams.

“We are finding harmful associations with iron within these low-risk alcohol consumption guidelines,” said Dr. Anya.

The study was published online on June 14 in the journal PLOS Medicine.

An opportunity for timely intervention?

Previous research suggests that higher levels of iron in the brain may be involved in the pathophysiology of Alzheimer’s and Parkinson’s disease. However, it is unclear whether deposition plays a role in alcohol’s effect on the brain and, if so, whether this could represent an opportunity for timely intervention with, for example, chelating agents.

The study included 20,729 study participants UK Biobankwhich recruited volunteers from 2006 to 2010. Participants had a mean age of 54.8 years and 48.6% were women.

Participants self-declared current consumption, previous consumption or no consumption of alcoholic beverages. For current consumers, the researchers calculated the total weekly number of UK units of alcohol consumed. One unit has eight grams. One drink usual in the United States has 14 grams. They categorized weekly consumption into quintiles and used the lowest as a reference point.

Participants had an MRI of the skull to determine iron levels in the brain. The areas of interest were brain structures deep in the basal ganglia.

Average weekly alcohol consumption was 17.7 units, higher than the UK guidelines for low-risk drinking. “Half the sample was drinking more than recommended,” said Dr. Anya.

Alcohol consumption was associated with markers of increased iron accumulation bilaterally in the putamen nucleus (beta [β] of 0.08 standard deviation [DP]; confidence interval [IC] from 95% from 0.06 to 0.09; P < 0.001]caudate nucleus (β 0.05; 95% CI 0.04 to 0.07; P < 0.001) and substantia nigra (β 0.03; 95% CI 0.02 to 0.05; P < 0.001).

worst performance

Drinking more than seven units (56 grams) weekly was associated with increased susceptibility to all brain regions except the thalamus.

Control for menopause did not change the associations between alcohol and susceptibility for any brain region. This was also the case when excluding blood pressure and cholesterol as covariates.

There were significant interactions with age in the putamen and caudate nuclei bilaterally, but not with sex, smoking, or Townsend’s deprivation index, which includes factors such as unemployment and living conditions.

To collect data on liver iron levels, participants underwent imaging of the abdomen at the same time as imaging of the skull. Dr. Anya explained that the liver is a primary storage center for iron, so it was used as “a sort of surrogate marker” of iron accumulation in the body.

The researchers showed an indirect effect of alcohol through systemic iron. A one-SD increase in weekly alcohol consumption was associated with an increase of 0.05 mg/g (95% CI 0.02 to 0.07; P < 0.001) on hepatic iron accumulation. In addition, a 1 mg/g increase in hepatic iron accumulation was associated with an increase of 0.44 (95% CI 0.35 to 0.52; P < 0.001) SD on left putamen susceptibility.

In this sample, 32% (95% CI from 22 to 49; P < 0.001) of the total effect of alcohol on left putamen susceptibility was mediated by higher systemic iron levels.

To minimize the impact of other factors that influence the association between alcohol consumption and brain iron accumulation — and the possibility that people with higher brain iron levels drink more — the researchers used Mendelian randomization, which considers genetically predicted alcohol intake. This analysis corroborated findings of associations between alcohol consumption and brain iron accumulation.

Participants performed a battery of cognitive tests, with trail-making tests that reflect executive function, puzzle tests that assess fluid intelligence or logic and reasoning, and task-based tests using the card game snap to measure reaction time.

The researchers found that the greater the accumulation of iron in certain brain regions, the worse the participants’ cognitive performance.

Patients should be aware of the risks of moderate alcohol consumption so they can make informed decisions about their consumption, said Dr. Anya. “They should be aware that 14 units of alcohol a week is not zero risk.”

new research

When commenting on the findings for the Medscape, Dr. Heather Snyder, Ph.D., vice president of medical and scientific relations at Alzheimer’s Associationcited the study’s large size as one of its strengths.

She noted that previous research has shown an association between higher iron levels and alcohol dependence and worse cognitive function, but the potential connection of brain iron levels, moderate alcohol consumption and cognition has not been studied to date.

“This article aims to analyze whether there is a potential biological link between moderate alcohol consumption and cognition through iron-related pathways.”

The authors suggest that more work is needed to understand whether alcohol consumption impacts iron-related biology to consequently affect cognition, said Dr. Heather. “While this study does not answer that question, it does highlight some important issues.”

The study authors received funding from the Wellcome Trust, Medical Research Council, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, British Heart Foundation (BHF) Center of Research Excellence, British Heart Foundation, NIHR Cambridge Biomedical Research Centre, United States Department of Veterans Affairs, China Scholarship Council and Li Ka Shing Center for Health Information and Discovery. Dr. Anya Topiwala reported having no relevant conflicts of interest.

PLOS Medicine. Published online July 14, 2022. Full text

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