Genetic Variant Significantly Increases Dementia Risk in Men, New Study Finds

Recent research indicates that men carrying a common genetic mutation have twice the likelihood of developing dementia over their lifetime compared to women. The study, published in the journal Neurology, analyzed data from the ASPREE trial, which involved over 19,000 healthy older adults in Australia and the United States. The focus was on the hemochromatosis (HFE) gene, which plays a role in regulating iron levels within the body. Specifically, the research examined whether variants in this gene could influence dementia risk.

The findings revealed that while most individuals with the variant, known as H63D, do not experience health issues, having two copies of this mutation markedly increases dementia risk in men. Approximately one in three people carry one copy of the H63D variant, and about one in 36 carry two copies. Interestingly, this increased risk was specific to men, with no significant association observed in women.

Professor John Olynyk from Curtin University explained that although having a single copy of the variant does not impact health, the presence of two copies more than doubles the risk of dementia among men. The study suggests that the genetic change influences brain pathways linked to dementia progression. Notably, the research found no direct link between iron levels in the blood and increased dementia risk, implying other mechanisms, such as inflammation and cellular damage, might be involved.

The findings could lead to more targeted screening approaches, as HFE gene testing is already common for diagnosing hemochromatosis in Western countries. Professor Olynyk highlighted that broader testing for men might be beneficial, potentially enabling earlier intervention. Meanwhile, Professor Paul Lacaze from Monash University emphasized that understanding why this genetic variant increases risk specifically in men could improve personalized prevention strategies.

Further research is necessary to uncover why this mutation affects males differently and to explore potential treatments that address the pathways disrupted by the gene variant. The study underscores the importance of genetic factors in dementia and highlights the potential for personalized medicine approaches in managing the disease.

The ASPREE trial, which initially aimed to assess the risks and benefits of daily low-dose aspirin, provided valuable insights into healthy aging and age-related diseases, including dementia. This collaborative effort involved multiple Australian research institutions and emphasizes the ongoing need to decode the genetic influences on neurodegenerative diseases.