Ground-breaking dementia research harnesses power of genomics

Participants from the Sax Institute’s 45 and Up Study have signed up for a genomics project that will investigate how a person’s genes affect their attempts to prevent cognitive decline.

The project is part of the Maintain Your Brain trial, which is testing whether healthy lifestyle behaviours can slow cognitive decline and, in the longer term, delay the onset of dementia.

More than 1000 people have volunteered to donate blood or saliva to the project since recruitment began in December.

“The response has been astounding, and we’re really grateful,” says Professor Henry Brodaty from UNSW Sydney’s Centre for Healthy Brain Ageing, which is leading the project.

Researchers will see if a person’s genotype interacts with their responsiveness to the Maintain Your Brain trial, says Prof Brodaty. “We’ll be looking at a person’s ‘polygenic risk score for dementia’, which summarises an individual’s genetic risk based on lots of different genetic variants, but we’ll be looking at particular genes as well.” For instance, if a person inherits the gene variant apolipoprotein E e4 from both parents, their risk of Alzheimer’s disease may be up to ten times higher than average, says Prof Brodaty.

“We may find out that your DNA sequence enhances your response to the Maintain Your Brain’s interventions, or that it decreases it.”

The volunteers are all part of the original Maintain Your Brain trial, which recruited more than 6,000 participants from the 45 and Up Study in 2018. The trial gave one group information on up to four areas – improving their exercise, diet, brain activity and mental health – over 12 months, and the other group got personalised online coaching in those areas. How many areas a person received information or coaching on were based on individual risk factors.

Lifestyle changes made by participants included following a plant-based Mediterranean diet and a tailored exercise program to maintain fitness, strength and balance, as well as taking part in brain training and depression or anxiety treatment to improve cognition. Participants’ cognitive ability was measured after one, two and three years.

The trial is ground-breaking because all the interventions were done online, making it low-cost to implement to the general population. Preliminary results appear to indicate positive results, especially for those receiving personalised coaching. Official results are expected to be published in the next few months, says Prof Brodaty. “The interventions done in the trial have the potential to delay the onset of dementia.”

Biospecimens donated to Maintain Your Brain’s project will also be added the 45 and Up Study’s growing biobank, to enable further research into the interplay between genes, other molecules, and dementia. “Blood markers for Alzheimer’s have recently been identified, which is really exciting, and that could be something for the future,” Prof Brodaty says.

He’s also hopeful he can get funding to monitor cases of dementia in Maintain Your Brain participants for another five years. “If we had more time, we could really see the effect of the trial on delaying dementia.”