A hidden dementia risk could affect one gender more

A recent Australian study has uncovered a significant link between a common genetic variant and an increased risk of dementia in men. Specifically, men who inherit two copies of the H63D variant in the HFE gene are more than twice as likely to develop dementia compared to those without this genetic makeup. Interestingly, this heightened risk was not observed in women.

The HFE gene plays a crucial role in regulating iron levels in the body. Mutations in this gene, such as the H63D variant, are associated with conditions like hereditary haemochromatosis — a disorder causing excessive iron absorption. While carrying one copy of the H63D variant is relatively common and typically harmless, about one in 36 individuals carry two copies, placing them at a significantly higher risk for dementia if they are male .

The study, published in the journal Neurology, analysed data from over 19,000 healthy older adults in Australia and the United States, collected as part of the ASPREE — ASPirin in Reducing Events in the Elderly — trial. Researchers found that men with two copies of the H63D variant had more than double the risk of developing dementia, while women with the same genetic profile did not exhibit an increased risk .

Professor John Olynyk from Curtin University, a co-author of the study, said having just one copy of this gene variant does not impact someone’s health or increase their risk of dementia.

“However, having two copies more than doubled the risk of dementia in men, but not women,” he explained.

He emphasised the need for further research to understand why this genetic variant affects men differently from women.

Interestingly, the increased dementia risk in men with the double H63D variant does not appear to be directly linked to iron levels in the blood. This suggests that other mechanisms, possibly involving inflammation or cellular damage in the brain, may be at play.

Given that the HFE gene is routinely tested in many Western countries, including Australia, when assessing individuals for haemochromatosis, these findings could have implications for broader genetic screening. Professor Olynyk suggests that such testing might be offered more broadly to men to identify those at higher risk for dementia.

With over 400,000 Australians currently living with dementia and about a third of them being men, understanding genetic risk factors is crucial. Co-author Professor Paul Lacaze from Monash University said understanding why men with the double H63D variant are at higher risk could pave the way for more personalised approaches to prevention and treatment.

This study underscores the importance of personalised medicine and the potential benefits of genetic screening in identifying individuals at increased risk for dementia, allowing for earlier interventions and tailored treatment strategies.

The number of Australians with dementia is projected to more than double by the year 2058.

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