A UK cohort study and Mendelian randomization (MR) suggested that moderate alcohol consumption [>7 units (56 g) alcohol weekly] was associated with markers of higher brain iron and worse cognitive function. The study included 20,729 UK Biobank participants (mean age 54.8 years, 48.6% female). Multiorgan susceptibility-weighted magnetic resonance imaging (~9.60 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (χ) and T2*, measures used as indices of iron deposition. Weekly alcohol consumption was 17.7 ± 15.9 units and with 2.7% of never drinkers. Quintile-based analyses found in those consuming >7 units (56 g) alcohol weekly, alcohol consumption was associated with markers of higher iron (χ) in putamen (β = 0.08 standard deviation, caudate (β = 0.05), and substantia nigra (β = 0.03) and lower iron in the thalami (β = −0.06). MR analyses suggested these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility, although the associations did not survive multiple testing corrections. A causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The findings support that there may be no safe level of alcohol consumption for brain health, and brain iron accumulation may be a potential mechanism for alcohol-related cognitive decline. Source: https://journals.plos.org/
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