Aspirin, Genes and Dementia
Daily aspirin failed to prevent dementia in one of the largest trials ever run in healthy older adults. A fresh look at the same volunteers' DNA suggests the drug may still help a narrow group. Monash University researchers report that low-dose aspirin was linked to a 70% lower dementia risk among people whose genes point toward high platelet counts.
Key Takeaways
- Among participants in the top 20% for a platelet-count genetic score, 1% of aspirin users developed dementia, compared with 3.3% on placebo.
- Major bleeding roughly doubled in the same group, and the authors call the finding hypothesis-generating, not a reason to start taking aspirin.
- The analysis used genetic data from 13,541 participants in the ASPREE trial and appears in Alzheimer's & Dementia.
The study, led by Dr Peter Fransquet of Monash's School of Public Health and Preventive Medicine, appeared in Alzheimer's & Dementia: The Journal of the Alzheimer's Association on September 24.
A Second Look at ASPREE
ASPREE, short for ASPirin in Reducing Events in the Elderly, randomly assigned healthy older adults to 100 mg of aspirin a day or a placebo. Across everyone enrolled, daily aspirin did not help older people stay healthy, and it showed no overall effect on dementia.
The Monash team returned to the trial's genetic data. Of 19,114 participants, 14,117 provided usable DNA, and the final analysis covered 13,541. The researchers screened 5,182 polygenic scores, which add up many small genetic effects, to see whether any of them changed aspirin's effect on dementia or major bleeding.
“Previous trials found aspirin didn't prevent dementia when everyone was considered together,” Fransquet said. “Our findings suggest there may be more to the story.”
Platelets, Not Alzheimer's Genes
The strongest signal came from scores linked to platelet count. Participants ranked in the top fifth on that score showed the 1% versus 3.3% split. Outside that group, dementia rates looked similar with or without aspirin.
The effect did not track with APOE or other known genetic risk factors for Alzheimer's disease and dementia. “Instead, it's pointing us towards platelet biology and gives us a new avenue to investigate,” Fransquet said.
The benefit came with a cost. In the same high-score group, major bleeding was about twice as common on aspirin, at 4.4% versus 2.1%, with a hazard ratio of 2.13. The scores also came from genetic studies of platelet count, not of platelet activation or clumping.
“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,” Fransquet said. He added: “If it holds up, the fact that aspirin is already cheap and widely available could make personalised dementia prevention a real possibility.”
A Narrow Opening for Prevention
The search for prevention tools grows more pressing every year. About 57 million people lived with dementia in 2021, and nearly 10 million new cases appear each year as populations age. Researchers are testing ideas ranging from a shingles vaccine that may protect the brain to ultrasound treatment, yet cheap and widely available options remain scarce.
Aspirin's bleeding risk keeps doctors cautious about prescribing it to healthy older people. Coverage aimed at clinicians points out that the bleeding signal rose alongside the dementia benefit in the very same genetic group. Long-standing cautions about aspirin in older adults still apply. Precision prevention would require a genetic test, a dedicated trial and a careful weighing of brain protection against bleeding.
Written by Alius Noreika