The results of a new large-scale study indicate that alcohol’s damaging effects on cognitive functions may be partly caused by increased iron accumulation in the brain.
There is growing evidence that even moderate alcohol consumption negatively impacts the brain, but the mechanisms underlying this are unclear. One possibility is that alcohol increases iron accumulation within the brain, damaging nerve cells. Very heavy alcohol consumption has been associated with iron accumulation in the brain, but it was unknown whether this also occurs in moderate alcohol drinkers.
To investigate this, researchers from Oxford Population Health led a study to investigate the relationship between alcohol intake and brain iron levels on almost 21,000 participants in the UK Biobank. The results have been published today in PLOS Medicine .
For each participant, brain iron levels were measured using magnetic resonance imaging whilst alcohol intake was assessed using a questionnaire on drinking habits. At the time of the brain scan, cognitive function was assessed using standard tests for executive function (mental skills that include working memory, flexible thinking, and self-control), fluid intelligence (comprehension, reasoning, and problem solving), and reaction time.
- Of the main sample, 3% did not drink alcohol at all, 95% were current drinkers, and 2% had drunk alcohol previously, but now stopped. The average weekly alcohol consumption was 17.7 units**, higher than current UK low-risk guidelines (<14 units weekly).
- Alcohol consumption above 7 units (56g) each week was associated with greater iron accumulation in the basal ganglia, a group of structures found deep within the white matter of the brain that perform various cognitive, emotional, and movement-related functions.
- Higher levels of iron in the basal ganglia were in turn associated with poorer executive function and fluid intelligence, and slower reaction speed. For instance, participants with higher levels of iron in the brain were slower at completing problem-solving tasks such as identifying the highest number in a list and working out family relationships.
- There was a significant interaction between alcohol consumption, age and iron accumulation in the brain, suggesting that alcohol may magnify how ageing affects the brain.
To investigate these findings further, the research team also assessed genetic variants that have previously been associated with alcohol consumption and alcohol use disorders in large-scale genome wide association studies.*** These genetic variants were found to be weakly associated with greater damage in the hippocampus (involved in learning and memory) and putamen (a region which controls limb movement), but this was not statistically significant after accounting for multiple testing.
According to the research team, one possible mechanism by which alcohol may raise brain iron levels is through suppressing the hormone hepcidin, which regulates blood iron levels. This would lead to greater absorption of dietary iron in the intestines. Alternatively, alcohol may increase the permeability of the blood-brain barrier to iron, or contribute to chronic inflammatory processes.
Lead researcher Dr Anya Topiwala (Oxford Population Health) said: ‘This study represents the largest investigation of moderate alcohol consumption and brain iron accumulation to date. Our results indicate that greater brain iron levels could be a potential mechanism for alcohol-related cognitive decline. Clarifying the pathological mechanisms by which alcohol acts upon the brain is vital not just for disease aetiology, but also to offer opportunities for intervention, for instance, iron chelation therapies that remove excess iron. However, it is important that these findings are validated in other populations, particularly those which are more ethnically diverse and socioeconomically deprived.’