Variant in HFE Gene Linked to Higher Dementia Risk in Men

A recent study published in Neurology has found that men carrying two copies of a common variant in the haemochromatosis (HFE) gene are more than twice as likely to develop dementia compared to women. The research used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, which included 19,114 healthy older adults from Australia and the United States. 

The HFE gene is important for regulating iron levels in the body. According to Professor John Olynyk from the Curtin Medical School, “one in three people carry one copy of the variant, known as H63D, while one in 36 carry two copies.” The study found that having a single copy of the H63D variant does not affect health or dementia risk. However, men with two copies faced more than double the risk of developing dementia, a pattern not observed in women. 

Professor Olynyk noted, “While the genetic variant itself cannot be changed, the brain pathways which it affects—leading to the damage that causes dementia—could potentially be treated if we understood more about it.” He also highlighted the need for further research to determine why the increased risk is seen in men but not women.

The HFE gene is already routinely tested when assessing haemochromatosis, a disorder causing excessive iron absorption. Professor Olynyk suggested that broader testing in men might be beneficial. Interestingly, the study found no direct link between iron levels in the blood and dementia risk, indicating that other mechanisms, such as inflammation and cell damage, may be involved.