Dementia: Widespread Genetic Variant Doubles Risk in Men

A common genetic variant (1 in 36 people have it) doubles the risk of dementia in men, but not in women . This was discovered by a team of Australian scientists, authors of a study published in 'Neurology'. A work that, according to the researchers, could contribute and improve and target prevention interventions, but which raises several questions to be answered. The first: why in males yes and in females no?

The scientists started with data from the Aspree study, a double-blind, randomised, placebo-controlled trial of daily low-dose aspirin - the so-called 'little aspirin' - in 19,114 healthy older adults in Australia and the US. Designed to assess the risks and benefits of daily low-dose aspirin in this cohort, Aspree generated a valuable database of information on ageing that has supported a wide range of other research. The authors used the information gathered by Aspree to investigate whether people with variants of the haemochromatosis (Hfe) gene, which is essential for regulating iron levels in the body , might be at increased risk of dementia.

John Olynyk of Curtin Medical School, a co-author of the study, says that 1 in 3 people carry one copy of the variant known as H63D, while 1 in 36 people have two copies. "Having just one copy of this genetic variant does not affect health or increase the risk of dementia. However, having two copies of the variant more than doubled the risk of dementia in men, but not in women ," Olynyk says. "Although the genetic variant itself cannot be changed, the brain pathways it affects, leading to the damage that causes dementia, could potentially be treated if we understood more about them." More research is needed, Olynyk says, for example to investigate why the variant increases the risk of dementia in males but not in females.

"The Hfe gene - continues Olynyk - is routinely tested in most Western countries, including Australia, when evaluating haemochromatosis, a disease that causes the body to absorb too much iron. Our results suggest that perhaps this test could be offered to men more widely." The researcher points out: "Although the Hfe gene is critical for controlling iron levels in the body, we found no direct link between blood iron levels", measurable through a simple blood sample, "and increased risk of dementia in affected men. This indicates" the existence of "other mechanisms at play, which could involve increased risk of brain injury, due to inflammation and cell damage in the body".

For Paul Lacaze of Monash University, a co-author of the study, the findings could help improve the prognosis for people at risk of developing dementia. "More than 400,000 Australians are currently living with dementia, around a third of whom are men," he notes. "Understanding why men with the double H63D variant are at greater risk could pave the way for more personalized approaches to prevention and treatment." "This study," Lacaze concludes, "is a great example of how different research groups and universities in Australia can work together effectively to deepen our understanding of these progressive diseases and, ultimately, improve the health of people around the world."

The work is the result of a synergy between Curtin University, Monash University, the University of Melbourne, the Royal Children's Hospital, Murdoch Children's Research Institute and the Fiona Stanley Hospital.