Men who carry two copies of a common genetic variant may face more than double the risk of developing dementia in their lifetime, according to new research published in the journal Neurology. The study, which analyzed data from the large-scale ASPREE trial, offers new insight into how genetics can influence brain health—especially in men.
The focus of the study was the HFE gene, which plays a critical role in managing iron levels in the body. One specific variant of this gene, known as H63D, is relatively common. About one in three people carry one copy of the variant, and about one in 36 people carry two copies.
According to Professor John Olynyk from Curtin Medical School, carrying one copy of the variant does not appear to affect dementia risk or overall health.
However, men who carry two copies were found to be more than twice as likelyto develop dementia compared to those without the variant. Interestingly, this increased risk was not seen in women, even if they carried two copies of the same gene.
“We found a significant link between this gene variant and dementia risk in men, but not in women,” said Professor Olynyk. “This suggests there are sex-specific factors at play, and we need more research to understand why.”
The HFE gene is already widely tested in Western countries, including Australia, as part of screening for haemochromatosis, a disorder that causes the body to absorb and store too much iron. While HFE mutations are known to affect iron metabolism, the study found no direct link between iron levels in the blood and dementia risk.
This suggests the gene may influence the brain through other means—possibly involving inflammation or cellular damage.
“Even though the gene is known for regulating iron, our findings suggest something else is happening in the brain that leads to damage and dementia in these men,” Professor Olynyk explained.
Professor Paul Lacaze from Monash University, a co-author of the study, believes the findings could pave the way for more personalized dementia prevention strategies. “Understanding why men with this genetic profile are at greater risk could help us design better ways to prevent or delay dementia in this group,” he said.
Dementia currently affects over 400,000 Australians, with about one-third of them being men. This new discovery may help explain some of the variation in how and when dementia develops in different individuals.
The data used in the study came from the ASPREE trial (ASPirin in Reducing Events in the Elderly), which enrolled over 19,000 healthy older adults in Australia and the U.S.
The trial initially examined whether daily low-dose aspirin could help prevent age-related disease, but it also produced a rich dataset that continues to support many new discoveries in aging and disease prevention.
“This study is a great example of how collaborative research using large-scale health data can uncover new clues about serious diseases like dementia,” said Professor Lacaze.
While the H63D genetic variant itself can’t be changed, the researchers hope that future work will lead to targeted treatments or prevention strategies aimed at reducing its harmful effects—especially in men. In the meantime, their findings suggest that routine genetic testing for HFE variants could play a role in assessing dementia risk, particularly for older men.
If you care about dementia, please read studies about Vitamin B9 deficiency linked to higher dementia risk, and flavonoid-rich foods could help prevent dementia.
For more information about brain health, please see recent studies that cranberries could help boost memory, and how alcohol, coffee and tea intake influence cognitive decline.
The research findings can be found in Neurology.
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