Moderate Alcohol Consumption May Cause Cognitive Decline

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by Marta Figueiredo, PhD |

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Drinking more than three beers or about three large glasses of wine per week is associated significantly with higher iron levels in several brain regions, which is linked to worse cognitive function.

That’s according to a study from the United Kingdom involving nearly 21,000 people — likely representing the largest investigation of moderate alcohol consumption and iron accumulation to date.

Iron accumulation in the brain has been linked previously to Parkinson’s disease and other neurodegenerative conditions.

“In the largest study to date, we found that drinking greater than seven units of alcohol weekly was associated with iron accumulation in the brain,” Anya Topiwala, MD, PhD, said in a press release. Topiwala, of the University of Oxford’s Big Data Institute in the U.K., is the study’s first author.

“Higher brain iron in turn is linked to poorer cognitive performance, such as executive function (problem solving) and fluid intelligence (puzzle tasks),” Topiwala said, adding that “iron accumulation could underlie alcohol-related cognitive decline.”

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These findings shed light on the potential underlying mechanisms of alcohol’s negative effects in brain health, the researchers noted.

Klaus Ebmeier, MD, one of the study’s authors and a professor of old age psychiatry at the University of Oxford, said: “This is one in a series of Oxford studies done in the large UK Biobank data set that suggest even ‘normal’ drinking comes with a risk for [aging], mental, and physical brain health.”

“Everyone who consumes alcohol needs to balance this against their potential enjoyment of having a drink,” Ebmeier added.

The study, “Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses,” was published in the journal PLOS Medicine.

Increasing evidence suggests that even moderate drinking negatively affects brain health. Topiwala, Ebmeier, and colleagues previously showed that moderate alcohol consumption is a risk factor for negative brain outcomes and cognitive decline.

Effects of too much iron

While the underlying mechanisms remain largely unknown, iron accumulation in the brain is viewed as a possible contributor, “as higher brain iron has been described in numerous neurodegenerative conditions including Alzheimer’s and Parkinson’s disease,” and “in alcohol dependence,” the researchers wrote.

However, whether brain iron levels differ by level of alcohol consumption is unclear.

Now, those two researchers, along with colleagues in the U.K. and the U.S., evaluated potential relationships between alcohol consumption and brain iron levels and whether higher brain iron accumulation represents a potential mechanism of alcohol-related cognitive deficits.

The study included 20,965 participants (48.6% female) from UK Biobank, a large-scale database containing genetic and health information from half-a-million people in the U.K. who were recruited from 2006 to 2010.

These participants, with a mean age of 54.8 years, had reported their own alcohol consumption at study entry (baseline). For current drinkers, the total weekly number of U.K. units of alcohol consumed was calculated by summing across beverage types.

Of note, one alcohol unit in the U.K. comprises about 8 grams of pure alcohol; a U.S. standard drink contains 14 g.

All participants had their brains scanned with magnetic resonance imaging (MRI) at a mean of 9.6 years after baseline; of those, 6,936 also underwent liver MRI. MRI scans were used to indirectly assess iron content in the brain and liver, which in this case was used as a marker of systemic iron, or iron levels throughout the body.

They also completed a series of simple tests to assess cognitive function at baseline and in online follow-up, at a mean of 5.8 years later.

Results showed that 2.7% of participants considered themselves nondrinkers and the average alcohol intake per week was 17.7 units, representing about 7.5 cans of beer or six large glasses of wine.

This intake was higher than current U.K. alcohol consumption recommendations to keep its health risks to a low level (fewer than 14 units weekly). U.S. guidelines recommend limiting daily alcohol consumption to two drinks or less in men and one drink or less for women.

Effects on the basal ganglia

Drinking more than seven units per week (56 g of pure alcohol) was associated significantly with markers of higher iron levels in the basal ganglia, a group of brain regions involved in movement, higher cognitive functions such as problem-solving, and emotion.

Alcohol consumption greater than 11 units weekly in men and 17 units in women was linked significantly to higher liver iron measured by MRI. Also, “systemic iron levels partially mediated associations of alcohol intake with brain iron,” the researchers wrote.

In addition, iron accumulation in some of these brain regions was associated significantly with worse cognitive function, namely slower executive function, lower ability to solve puzzles, and slower reaction times.

These findings point to brain iron accumulation as a potential mechanism behind alcohol’s negative effects in cognitive function.

Given the prevalence of moderate drinking, even small links with cognitive decline can have substantial impact across whole populations. As such, interventions to reduce alcohol consumption may benefit the general population.

Among the study’s limitations, the researchers emphasized the indirect measure of iron levels by MRI, which may be influenced by other factors, and the self-reporting method for alcohol intake, which may have resulted in underestimations. However, the latter was considered the only feasible method to determine intake in such a large group of people.

Also, “it is unclear how our findings generalize to other populations, particularly those which are more ethnically diverse and socioeconomically deprived,” the team wrote.

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