It’s in your DNA—and for thousands of men, it could quietly double their chances of developing dementia. New research sheds light on one genetic variant that puts males at significantly greater risk than females.
Key Points at a Glance
- A common gene variant, H63D in the HFE gene, doubles dementia risk in men
- One in 36 people carry two copies of this variant; one in three carry one copy
- Women with the same genetic makeup do not show increased risk
- Findings challenge current understanding of dementia and iron metabolism
- Study suggests future potential for gender-specific dementia prevention strategies
Dementia already affects hundreds of thousands of lives, but a new study has uncovered a hidden factor that could be silently raising the stakes for men. Scientists have identified a genetic variant that, when inherited in double dose, more than doubles the risk of developing dementia—for men only.
Published in Neurology, the study used data from the ASPREE trial, a massive clinical study on healthy aging, to investigate the role of the HFE gene. This gene regulates how the body handles iron—and when its H63D variant is inherited from both parents, it can subtly, but significantly, alter brain health in aging men.
“While one copy of the H63D variant doesn’t seem to affect health, two copies are a different story—at least for men,” said Professor John Olynyk from Curtin Medical School. “We saw more than double the risk of dementia compared to men without the variant. Interestingly, women were unaffected.”
One in 36 people carry this double genetic variant. That’s not rare—it means tens of thousands of men may unknowingly be at risk. The surprising part? The study found no direct correlation between blood iron levels and dementia risk. So it’s not about too much iron clogging the system. Something else is happening—something subtler, and perhaps more dangerous.
“This suggests other pathways are at play,” Olynyk explained. “Possibly involving inflammation and cellular damage that gradually builds up over time.” The precise biological mechanics remain unclear, but the gender difference in effect is impossible to ignore.
Currently, the HFE gene is routinely tested when screening for haemochromatosis—a disorder that causes iron overload—but the new findings suggest its broader impact has gone under the radar. And it could be time to reconsider who gets tested, and why.
“It’s too soon to recommend population-wide genetic screening,” said co-author Professor Paul Lacaze from Monash University. “But this gives us an avenue for more targeted research and potentially, gender-specific approaches to dementia prevention.”
The findings are a striking reminder of how personalized medicine might one day transform care. One person’s DNA isn’t just a blueprint—it’s a risk profile. And if we can understand the genetic factors behind neurodegenerative diseases, we may be able to slow or prevent them before symptoms emerge.
The ASPREE trial itself was a monumental effort, involving over 19,000 older adults from Australia and the U.S., originally designed to assess the effects of low-dose aspirin. But its legacy is growing far beyond that, offering a goldmine of insights into the science of healthy aging.
Collaborators from Curtin University, Monash University, the University of Melbourne, and several major hospitals hope this research is only the beginning. If the mechanisms linking the H63D variant and male dementia risk can be decoded, it could open doors to new treatments or even early interventions that are sex-specific.
For now, it’s a wake-up call: our genes hold secrets we’re only beginning to decipher, and those secrets may not be the same for everyone.
Source: Curtin University News
