Gene variant doubles male dementia risk

New research conducted by Curtin University, Monash University, The University of Melbourne, The Royal Children’s Hospital, Murdoch Children’s Research Institute and Fiona Stanley Hospital has found that men who had variants in the haemochromatosis gene are twice as likely than women to develop dementia in their lifetime.

The study included 12,174 unrelated, healthy participants of European ancestry who were aged 70 years or older, and had no history of cardiovascular disease, dementia, or cognitive decline at enrolment.

Co-author Professor John Olynyk said one in three people carry one copy of the variant – known as H63D – which does not impact someone’s health or increase their risk of dementia.

However, one in 36 carry two copies which more than doubled the risk of dementia in men, he explained. This increased risk was not seen in women who carry two copies of the gene, and Professor Olynyk said further research would need to be done to understand why it only increases the risk for males.

He said he will also be linking up with established dementia researchers in WA at Edith Cowan and Curtin Universities to try and dissect out why 10 per cent of individuals with the p.H63D homozygosity develop dementia after the age of 70 years but 90 per cent do not.

“Understanding this may give us clues as to what might be possible as a preventative approach. We will also look at the way the gene variant may increase the susceptibility to brain injury in cell or other model systems,” he told CCR.

“The HFEgene is routinely tested for in most Western countries including Australia when assessing people for haemochromatosis – a disorder that causes the body to absorb too much iron. Our findings suggest that perhaps this testing could be offered to men more broadly,” he said.

“While the HFEgene is critical for controlling iron levels in the body, we found no direct link between iron levels in the blood and increased dementia risk in affected men.

“This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body.”

Co-author Professor Paul Lacaze, from Monash University, said the findings could help improve outcomes for people at risk of developing dementia.

“More than 400,000 Australians are currently living with dementia, with around a third of those being men. Understanding why men with the double H63D variant are at higher risk could pave the way for more personalised approaches to prevention and treatment,” Professor Lacaze said.

The research project used data from the ASPirin in Reducing Events in the Elderly trial – a double-blind, randomised, placebo-controlled trial of daily, low-dosage Aspirin.

The ASPREE trial involved 19,114 healthy older people from Australia and the United States and was originally intended to evaluate the risks versus benefits of Aspirin but also created a vast amount of healthy ageing data.

The dementia research was published in Neurology.

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