Low-Dose Aspirin and Dementia: A Possible Genetic Benefit, With Bleeding Risks

The headline finding is striking: in one genetic subgroup, daily low-dose aspirin was associated with roughly 70% lower relative dementia risk. But the same participants faced about twice the rate of major bleeding. For clinicians, the result is best read as a signal for further research—not a reason to start aspirin for dementia prevention.

The study, published in Alzheimer’s & Dementia, reanalyzed data from around 5,000 participants in the ASPREE trial. Its focus was whether genetic differences could help explain why earlier research found no overall dementia-prevention benefit from aspirin.

A subgroup result beneath a neutral trial

ASPREE compared daily 100-milligram aspirin with placebo in healthy older adults. The 2018 trial found no significant benefit in preventing dementia. A subsequent analysis of ASPREE data likewise found no significant reduction in Alzheimer’s disease, dementia, mild cognitive impairment, or cognitive decline.

The newer analysis examined participants’ polygenic scores, which estimate genetic predispositions using DNA data. Researchers found a possible benefit among people in the top 20% for a genetic score associated with platelet count. Platelets help blood clot, and high platelet activity can contribute to clotting.

Alexander Zubkov, M.D., a board-certified neurologist and physician with 1MD Nutrition, said about 1% of people in that group developed dementia while taking aspirin, compared with 3.3% of those given placebo. That amounts to an approximate 70% reduction in relative risk. Among the other 80% of participants, aspirin showed no dementia benefit.

That percentage needs context. The absolute difference in dementia cases was about 2.3 percentage points, and the subgroup also had more major bleeding. Luke Sorrell, M.D., a board-certified internist in longevity medicine and founder of Sorrell MD, characterized the balance as central to interpreting the result: bleeding roughly doubled in the same group that appeared to benefit.

Why platelet biology could matter

The proposed connection is biological, though the study does not establish exactly how aspirin might affect dementia risk. Platelets help form clots and release chemical signals involved in inflammation. Aspirin reduces platelet activation and inflammation, Zubkov explained.

Tiny clots and damage to small blood vessels in the brain can contribute to dementia. Researchers suggest aspirin might limit that damage in people genetically predisposed to greater platelet activity. The finding concerns possible prevention; it does not show that aspirin treats dementia once it develops.

That distinction matters because the results don’t overturn the broader trial evidence. Across the full ASPREE population, low-dose aspirin did not significantly prevent dementia. The signal emerged only after researchers analyzed genetic differences, and it applies to a subset identified by a specialized score.

A genetic score isn’t a routine blood result

The score used in the study estimates inherited tendency toward a higher platelet count. It does not tell someone’s current platelet level. A person with a high score could have a normal platelet count on standard bloodwork, Sorrell said.

Likewise, an elevated platelet count on a routine test can reflect temporary conditions such as iron deficiency, inflammation, infection, or recovery from surgery. Sorrell cautioned against drawing conclusions from a recent complete blood count: the study’s genetic measure and a lab result answer different questions.

Polygenic testing is becoming more available, but the analysis involved a relatively small subgroup within existing trial data. Researchers need to reproduce the finding, ideally in a dedicated trial, before it can guide care. Sorrell also advised against using consumer DNA files with online calculators to make a personal diagnosis.

Bleeding remains a major trade-off

Regular aspirin use can cause internal bleeding, most often in the stomach and, more rarely, in the brain. The risk rises with age and can be higher for people with a history of ulcers or gastrointestinal bleeding, kidney disease, uncontrolled blood pressure, or heavy alcohol use. Blood thinners, ibuprofen and naproxen, SSRIs, and steroids can also raise bleeding risk, Sorrell said.

Current U.S. Preventive Services Task Force guidance recommends against starting low-dose aspirin for primary prevention in adults 60 and older because the bleeding risk offsets the benefit. The new analysis doesn’t change that guidance. People already prescribed daily aspirin after a cardiac event shouldn’t stop taking it based on this study; they should discuss treatment with their doctor.

For now, the potential benefit cannot be weighed for an individual without the genetic analysis, and the study doesn’t establish that testing should lead to aspirin use. The finding is an early example of how a treatment with no apparent average benefit might warrant a closer look in a genetically defined group—but its potential harm appears in that same group.

Established ways to reduce dementia risk

While researchers test whether genetic profiles can guide prevention, several modifiable factors already have evidence behind them. The 2024 Lancet Commission estimated that nearly half of dementia cases are linked to 14 modifiable factors. Measures highlighted by Zubkov include:

• Managing high blood pressure and high LDL cholesterol
• Getting regular physical activity
• Addressing hearing and vision problems
• Getting sufficient sleep
• Limiting smoking and alcohol consumption
• Seeking mental health care and maintaining social connections
• Protecting against head injuries

The aspirin result points toward more personalized prevention, but it needs replication and a dedicated trial before it can inform routine decisions. Until then, the strongest practical takeaway is to manage established risk factors and treat aspirin as a medication whose possible benefit must be weighed against its bleeding risk.