A common genetic variant is linked to a doubled dementia risk for older men, a recent analysis in Neurology suggests.

The study used data from Aspirin in Reducing Events in the Elderly (ASPREE), which followed elderly patients in the United States and Australia with no history of cardiovascular disease, dementia or cognitive decline between 2010 and 2017.

Researchers focused on 12,174 Australians of European ancestry over age 70, and looked for variants in the HFE gene. The gene is critical to regulating the body’s iron levels, and variants are common among people of European descent.

Those who carry two copies of the p.C282Y variant in the HFE gene can develop hemochromatosis, a condition that causes iron overload in the body, and resulting conditions such as liver cirrhosis, liver cancer, frailty, arthritis and dementia.

One in 3 people carry a gene variant called H63D, and 1 in 36 carry two copies, John Olynyk, a professor at the Curtin Medical Research Institute in Perth, Australia, says in a news release about the new study.

“Having just one copy of this gene variant does not impact someone’s health or increase their risk of dementia. However, we found having two copies of the variant more than doubled the risk of dementia in [previously healthy] men, but not women,” Olynyk says.

Overall, men with two copies of the H63D HFE variant had a 2.39 higher incidence of dementia than those without variants in the HFE gene. No similar association was seen in women.

Men in the study had “significantly higher” ferritin (iron) levels than women, as expected, but the study did not find an association between ferritin levels at baseline and the risk of a person developing dementia.

The study builds on earlier evidence that variants in the HFE gene may play a role in dementia. While the p.C282Y variant causes dementia through the development of iron overload, the p.H63D variant in the same HFE gene may cause brain inflammation and damage leading to dementia in the absence of overt iron overload, the researchers write. The reason behind the difference in dementia risk between men and women was not clear.