For years, the verdict on low-dose aspirin and dementia has been disappointing. Large trials found it did not prevent the condition when older people were considered as one big group. But new research from Monash University suggests the full picture may be more complicated, and that a person’s genetic makeup could matter.
The stakes are considerable. Dementia Australia estimates 446,500 Australians are living with dementia in 2026, a figure projected to pass one million by 2065. No medications are currently approved for preventing the condition, so any affordable, accessible option would be significant.
“If it holds up, the fact that aspirin is already cheap and widely available could make personalised dementia prevention a real possibility,” said lead author Dr Peter Fransquet, a Research Fellow at Monash’s School of Public Health and Preventive Medicine.
For now, the message is one of cautious interest rather than action. The research offers a new lead on an old drug, and a reminder that the same treatment may not work the same way for everyone.
In the study, published in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association, researchers examined more than 13,500 participants, who were aged 70 and over, or 65 and over for some US minority groups, and who were randomly assigned to take daily low-dose aspirin or a placebo.
Rather than testing a single genetic theory, the team took a broad approach.
They screened thousands of publicly available polygenic scores, which combine many small genetic variations to estimate a person’s inherited tendency towards a trait or disease. After quality checks, 1848 scores were tested to see whether any changed how aspirin affected dementia risk.
One theme stood out. Scores linked to platelet count, the tiny blood cells involved in clotting, appeared far more often among the strongest results than chance would predict.
The researchers split participants into five equal groups, from the lowest to the highest genetic tendency towards a high platelet count. The group with the highest tendency, the top fifth, showed a striking result.
In that group, only 1 in 100 people taking aspirin developed dementia, compared with about 3 in 100 people taking the placebo. Put another way, the risk was roughly 70 per cent lower for those on aspirin.
For the other four groups, aspirin made no clear difference. In some of the lower groups, aspirin looked neutral or even slightly worse for dementia risk, though the numbers were too small to say for sure. In other words, aspirin did not seem to help most people, but it may have helped a specific group.
There was a significant catch. In the same high platelet group, major bleeding occurred in 4.4 per cent of people taking aspirin, compared with 2.1 per cent of those on the placebo.
Based on the observed rates, roughly 44 people would need to take aspirin for one to avoid dementia, and the same number for one to experience a major bleed. There was no difference in overall death rates between the two groups.
Dr Fransquet said the findings hint at a more personalised path forward.
“Previous trials found aspirin didn’t prevent dementia when everyone was considered together,” he said. “Our findings suggest there may be more to the story.”
“It raises the possibility that genetics could one day help us identify who may benefit from a preventive treatment, rather than taking a one-size-fits-all approach.”
Interestingly, the effect was not tied to the best-known genetic risk factors. The APOE gene, the strongest common genetic risk factor for Alzheimer’s disease, showed no interaction with aspirin, and neither did scores designed to predict dementia risk directly.
“What’s particularly interesting is that the signal wasn’t linked to the established genetic risk factors for Alzheimer’s disease and dementia,” Dr Fransquet said. “Instead, it’s pointing us towards platelet biology and gives us a new avenue to investigate.”
The researchers stress that this is a hypothesis-generating study. It was a post hoc analysis, meaning the question was explored after the trial ended, and testing so many genetic scores raises the chance that the strongest result overstates the true effect.
Participants were also followed for a median of about 4.6 years, which is short given how slowly dementia develops, and the group was predominantly of European ancestry. Because ASPREE is the only large aspirin trial of its kind with dementia outcomes and genetic data, finding an independent group to confirm the result will be difficult.
“We now need to confirm the finding in other studies and ultimately test it in a trial designed specifically for people with this genetic profile,” Dr Fransquet said.
He was clear about what the findings mean for the public. “People shouldn’t start taking aspirin to prevent dementia based on this study without consulting with their doctor, particularly given the increased risk of serious bleeding.”
