Aspirin linked to fewer dementia cases in genetic subgroup, but serious bleeding doubled

A genetic finding comes with a matching bleeding warning

Among older adults with a particular genetic profile, dementia developed in 1% of those taking aspirin and 3.3% of those taking a placebo. Serious bleeding moved in the opposite direction: 4.4% of aspirin users experienced major bleeding, compared with 2.1% receiving placebo.

Those findings, announced by Monash University on 29 September 2026, put the promise and danger of a possible approach to dementia prevention side by side. The reduction in dementia and the increase in major bleeding were both 2.3 percentage points in the genetic subgroup studied.

The analysis examined genetic data from 13,541 participants in ASPREE, the Aspirin in Reducing Events in the Elderly trial. Its strongest finding involved people in the highest 20% of a genetic score associated with platelet count. Platelets are small blood components that help form clots and stop bleeding.

Monash University's research announcement describes an association with about 70% lower relative dementia risk in that group. Researchers want the result checked independently and then tested in a trial designed specifically for people with this genetic profile. They advise against starting aspirin for dementia prevention without consulting a doctor.

Who took part in the aspirin trial?

ASPREE compared 100 milligrams of aspirin daily with a placebo, a tablet without the active medicine. Participants were generally healthy older adults without previous cardiovascular disease, dementia or physical disability when they entered the trial.

Eligibility began at age 70 in Australia and the United States, or age 65 for participants from minority groups in the United States. In the genetic analysis, the average age was 75 and 54.8% of participants were women. The median follow up was 4.6 years, meaning half were followed for less time and half for longer. During follow up, 345 participants developed dementia.

The research appeared in Alzheimer's & Dementia: The Journal of the Alzheimer's Association under the title Platelet count polygenic scores may modify the effect of aspirin in primary prevention of dementia. Researchers from Monash University and the University of Tasmania participated.

Earlier trials found no dementia prevention benefit when participants were considered together. This analysis returned to the ASPREE data to investigate whether inherited differences might help explain why the result varied among participants.

How did researchers identify the genetic group?

The team screened 5,182 genetic scores, of which 1,848 passed quality checks. A genetic score combines information from many variations in DNA into a single measure. Here, the most informative scores concerned inherited influences on platelet count.

Researchers initially found 112 scores suggesting that aspirin's relationship with dementia varied according to genetics. After a statistical correction for the large number of comparisons, three closely related scores associated with platelet count remained significant.

That correction matters because searching thousands of possibilities creates opportunities to find a striking pattern by chance. The correction makes the finding more persuasive, while independent research remains the next step.

Participants were ranked by their platelet count genetic score. The clearest difference appeared in the highest fifth of that ranking. This classification uses DNA information associated with platelet count; an ordinary blood test measures the platelets circulating in a person's blood at that moment.

The finding emerged from a later analysis of an existing trial. ASPREE was originally designed to test aspirin in older adults, rather than specifically recruiting people in this genetic category. A new trial could select that group in advance and directly test the proposed benefit and its risks.

What does a 70% reduction mean?

For every 1,000 people with the genetic profile, the reported percentages correspond to about 10 dementia cases among aspirin users and 33 among placebo recipients during the study period. The difference is approximately 23 fewer cases per 1,000 people.

The widely cited 70% figure describes the reduction relative to the placebo group's dementia rate. Moving from 3.3% to 1% is a fall of 2.3 percentage points, which is about 70% of the starting rate. Both figures describe the same comparison, but the percentage point difference helps readers understand how many people were affected.

A calculation that also considered when dementia developed produced a hazard ratio of 0.28. A hazard ratio compares how frequently an outcome occurs over time in two groups; a value below one indicates a lower rate in the aspirin group. Its 95% confidence interval was 0.15 to 0.52, showing the statistical uncertainty around the estimate.

Dr Peter Fransquet, the lead author and a research fellow at Monash's School of Public Health and Preventive Medicine, explained why the team looked beyond the result for all participants:

Previous trials found aspirin didn't prevent dementia when everyone was considered together,

Fransquet said the genetic subgroup offered a different pattern:

In people with this particular genetic profile, we saw substantially fewer cases of dementia among those taking aspirin.

Why the bleeding figures matter just as much

Major bleeding affected the equivalent of about 44 people per 1,000 taking aspirin, compared with 21 per 1,000 receiving placebo in the same genetic subgroup. That is approximately 23 additional people experiencing major bleeding per 1,000.

The bleeding hazard ratio was 2.13, with a 95% confidence interval of 1.36 to 3.34. In plain terms, the rate of major bleeding over time was a little more than twice as high among aspirin users.

Aspirin makes platelets less able to stick together, which helps explain why bleeding is a central safety concern. A medicine that changes clotting can have serious consequences even when the daily dose is small.

The equal percentage point differences put two different health outcomes into view. Dementia can bring lasting problems with memory, thinking and independent living. Major bleeding can require urgent treatment. A future trial would need to assess the severity, timing and consequences of both, alongside any benefit to daily life. Deaths from all causes did not differ between the aspirin and placebo groups in this subgroup analysis.

Why platelet biology is drawing attention

Previous research has connected platelet activation and aggregation with dementia. Activation means platelets become ready to respond, while aggregation means they gather together. Scientists have had less certainty about how a person's platelet count relates to dementia.

The genetic finding directs attention toward that part of blood biology. Researchers found no significant interaction between aspirin and APOE, a gene associated with Alzheimer's risk, or with genetic scores for Alzheimer's disease and dementia.

Fransquet described the result as a reason to explore a different biological route:

What's particularly interesting is that the signal wasn't linked to the established genetic risk factors for Alzheimer's disease and dementia,

The relationship also appeared concentrated at the upper end of the platelet score ranking. Across the full range of scores, the platelet score was not significantly associated with dementia, either among participants considered together or among those receiving placebo.

Dr Thomas Holland, a physician scientist at Rush University who was not involved in the study, described platelet biology's role as:

only a proposed mechanism rather than a proven explanation,

Researchers therefore still need to explain how the inherited platelet characteristics, aspirin and dementia might be connected.

What needs to happen before treatment advice changes?

Fransquet and his colleagues want other studies to check whether the association appears again, including in other populations. They then want a clinical trial designed specifically for people with this genetic profile.

A trial that selects participants in advance would address the central practical question: whether prescribing aspirin to that group produces enough benefit to justify the bleeding risk. The age and health of ASPREE participants also matter when considering who might eventually be eligible for such an approach.

No date was given for a dedicated trial. Genetic testing to choose aspirin for dementia prevention remains a research possibility, and the authors say the finding is insufficient to change aspirin recommendations.

Fransquet set out the next steps directly:

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.

What should older adults and families take from this?

Dementia Australia estimates that 446,500 Australians are living with dementia in 2026 and projects that the number will exceed one million by 2065. That would be more than twice the current estimate, explaining the interest in prevention strategies that might be affordable and widely accessible.

Aspirin's low cost makes the finding attractive, but its bleeding risk is already visible in the same results. For someone considering the medicine, the immediate step is a discussion with a doctor about their health, current medicines and reasons for treatment.

Fransquet's warning was explicit:

People shouldn't start taking aspirin to prevent dementia on the basis of this study without consulting with their doctor, particularly given the increased risk of serious bleeding.

The study offers a specific direction for research: testing whether inherited differences in platelet biology can help identify people who respond differently to aspirin. For patients today, the decision remains grounded in individual medical advice while that research proceeds.

Key Points

• The analysis used genetic data from 13,541 older ASPREE participants, with a median follow up of 4.6 years.
• In the highest fifth of a platelet count genetic score, dementia occurred in 1% taking aspirin and 3.3% taking placebo.
• Major bleeding occurred in 4.4% taking aspirin and 2.1% taking placebo in that same subgroup.
• The absolute differences were 2.3 percentage points for both fewer dementia cases and more major bleeding.
• Researchers want independent confirmation and a trial designed for people with this genetic profile.
• People should consult a doctor before considering aspirin for dementia prevention.