Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.
Level 3 - non-randomized controlled study
Observational cohort analysis with Mendelian randomization
PubMed 35834561 · doi:10.1371/journal.pmed.1004039
What was done
The authors analyzed 20,729 UK Biobank participants (mean age 54.8 ± 7.4 years, 48.6% female) who self-reported alcohol intake at baseline (2006–2010). Multiorgan MRI was conducted 9.60 ± 1.10 years later to quantify iron accumulation in brain regions (putamen, caudate, hippocampi, thalami, substantia nigra) and liver using quantitative susceptibility mapping (QSM, χ) and T2*. Cognitive testing evaluated executive function (trail-making test), fluid intelligence (puzzles), and reaction time. Observational findings and causal mediation through liver iron were compared against 2-sample Mendelian randomization (MR) of genetically predicted alcohol intake and alcohol use disorder.
What was found
Alcohol intake was associated with higher iron markers (χ) in the putamen (β = 0.08 SD [95% CI 0.06 to 0.09], p < 0.001), caudate (β = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (β = 0.03 [0.02 to 0.05], p < 0.001), and lower iron in the thalami (β = -0.06 [-0.07 to -0.04], p < 0.001). These differences emerged in individuals drinking >7 units (56 g) weekly. Liver iron was elevated at >11 units (88 g) weekly and partially mediated brain iron associations. Higher basal ganglia iron correlated with slower executive function, lower fluid intelligence, and slower reaction times. In MR analyses, positive associations between genetically predicted alcohol measures and brain iron markers were weak and did not survive multiple testing corrections.
Why it matters
This study provides evidence that moderate alcohol consumption exceeding 7 units per week is linked to increased brain iron accumulation, identifying a potential biological pathway for alcohol-related cognitive impairment.
Limits
Brain MRI indices (χ and T2*) reflect myelin alterations in addition to iron deposition. Alcohol intake was self-reported at baseline, and Mendelian randomization results were weak, non-robust to multiple testing corrections, and subject to potential genetic pleiotropy.
Cited by
- supports In a UK cohort of over 20,000 participants, consuming more than seven units of alcohol per week was associated with higher brain iron levels and worse cognitive function.