Aspirin and Dementia: A Genetic Clue, and a Catch

Low-dose aspirin is one of the cheapest and most widely used drugs in the world, so any hint that it could help protect the aging brain gets attention. The catch is that the big trials so far have been disappointing: when older adults are studied as one group, aspirin does not prevent dementia. A new analysis from Monash University suggests that this overall result may hide something. In one genetically defined slice of the participants, aspirin looked very different – and so did its risks.

Looking inside a trial that found nothing

The data come from ASPREE (Aspirin in Reducing Events in the Elderly), a large randomized, placebo-controlled trial of low-dose aspirin in older adults. The researchers used genetic data from 13,541 participants and asked a simple question: could differences in people’s DNA explain why aspirin might help some and not others?

To find out, they screened 5,182 polygenic scores from a public catalog. A polygenic score adds up the small effects of many genetic variants into a single number that estimates a person’s inherited tendency toward a trait. For each score, the team checked whether it changed how aspirin affected dementia and major bleeding compared with placebo.

The platelet signal

The strongest result came from scores built to predict platelet count. Platelets are the small blood cell fragments that help form clots. Participants were ranked by their score, and the top 20 percent were compared with everyone else.

In that top group, 1 percent of people taking aspirin developed dementia, against 3.3 percent of those on placebo. That works out to roughly a 70 percent lower relative risk; in the paper’s terms, a hazard ratio of 0.28. Outside that top group, dementia rates were similar with aspirin and placebo, which fits with the trial’s original null result.

The authors point out that the signal did not involve the well-known genetic risk factors for Alzheimer’s disease. Instead it points toward platelet biology, an area where researchers have already linked platelet activation and clumping to dementia, while the role of platelet count itself has been much less clear.

The catch

In the same genetic group, major bleeding occurred in 4.4 percent of people taking aspirin and 2.1 percent of those on placebo. Put the two sets of numbers side by side and the absolute differences are strikingly close: about 2.3 percentage points fewer people with dementia, and about 2.3 percentage points more with major bleeding. That is simple arithmetic on the reported figures, not a conclusion from the study, and the two outcomes are not equal in severity or in how patients weigh them. But it shows why a headline of “70 percent lower risk” tells only half of the story.

Why caution is warranted

·         It is a secondary look at an existing trial. ASPREE was not designed to test aspirin in people grouped by platelet-count genetics. This is a post hoc analysis.

·         Many scores were tested. When thousands of scores are screened, some will look significant by chance, which is why corrections for multiple testing matter. The authors themselves describe the results as hypothesis-generating and in need of validation.

·         The scores are a proxy. They estimate genetic tendency toward a higher platelet count; they are not direct measurements of platelet activity in the individual.

·         Replication comes first. The lead author says the finding must be confirmed in other studies and then tested in a trial built specifically for people with this genetic profile.

What it could mean

If the result holds up, it would be a textbook case of personalized prevention: a cheap, familiar drug that is useless on average but useful for a genetically identifiable group, whose bleeding risk could be weighed against the benefit before anyone takes it. If it does not hold up, it will be a useful reminder of how easy it is to find patterns in large genetic datasets.

For now, the researchers are clear that nobody should start taking aspirin to prevent dementia on the basis of this study, and that anyone considering it should talk to their doctor first, especially given the bleeding risk.

Sources

·         Original press release: Monash University, Genetic analysis reveals potential benefit of aspirin for reducing dementia risk (29 September 2026)

·         Original journal paper: Fransquet PD, Yu C, Tran C, et al. Platelet count polygenic scores may modify the effect of aspirin in primary prevention of dementia. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 2026. DOI: 10.1002/alz.71817

This post is for general information and is not medical advice. Talk to a doctor before starting or stopping any medication. 

Source: Aspirin and Dementia: A Genetic Clue, and a Catch