Low-Dose Aspirin and Dementia: A Genetic Signal Comes With Bleeding Risks

Aspirin’s dementia signal appeared in one genetic subgroup

Low-dose aspirin was associated with fewer dementia cases among older adults with a particular genetic profile in a new analysis of the ASPREE trial. The finding offers a possible explanation for why earlier studies saw no overall benefit: an effect in a smaller group may disappear when researchers average results across everyone.

The possible benefit came with a clear trade-off. The same subgroup had about twice the rate of major bleeding while taking aspirin. For now, the result is a research signal that needs replication, not a basis for starting daily aspirin.

The study, published in Alzheimer’s & Dementia, examined genetic data from around 5,000 ASPREE participants. Researchers looked at polygenic scores, which estimate genetic predisposition to traits or disease. Participants whose scores placed them among the top 20% for a genetic tendency linked to higher platelet counts appeared to benefit most.

In that group, about 1% of participants taking aspirin developed dementia, compared with 3.3% of those given placebo. Alexander Zubkov, M.D., a board-certified neurologist and physician with 1MD Nutrition, described that as a roughly 70% reduction in relative risk. For the other 80% of participants, he said, aspirin showed no dementia benefit.

Why earlier trial results looked different

The finding revisits a question researchers have studied for years: could aspirin help prevent dementia by reducing inflammation? Aspirin affects platelets and inflammation, both of which have been considered relevant to processes involved in Alzheimer’s disease and other forms of dementia.

Earlier results did not show an overall protective effect. In the 2018 ASPREE trial, healthy older adults who took 100 milligrams of aspirin daily had no significant dementia-prevention benefit compared with those who received placebo. A later analysis of ASPREE data likewise found no significant reduction in Alzheimer’s disease, dementia, mild cognitive impairment, or cognitive decline.

The new analysis asks whether those averages concealed a difference between people with different genetic profiles. Its results suggest that may be possible, but they don’t establish that aspirin prevents dementia in people identified by this score. The study examined a subgroup within existing trial data; confirming the result would require further research, including a dedicated trial.

A genetic score isn’t a routine blood test

The genetic profile in the study reflects an inherited tendency associated with platelet count. It doesn’t mean a person necessarily has a high platelet count on a standard blood test. Luke Sorrell, M.D., a board-certified internist in longevity medicine and founder of Sorrell MD, emphasized that someone with the genetic score could have normal platelet results in routine lab work.

And the reverse is true: a high platelet count on a blood test doesn’t show that someone has the genetic profile studied. Sorrell said elevated counts can be temporary and may be associated with iron deficiency, inflammation, infection, or recovery from surgery. A routine complete blood count can’t identify who might fall into the study’s subgroup.

Genetic testing that includes polygenic scores is becoming more available, Sorrell said, but these findings still need replication. He cautioned against using consumer DNA files with online calculators to try to diagnose oneself. Even if testing can identify a genetic tendency, that alone wouldn’t establish whether aspirin’s benefits outweigh its risks for an individual.

How platelets might connect aspirin to dementia risk

Platelets help blood clot and also release chemical signals involved in inflammation. Aspirin blocks platelet activation and can reduce inflammation, Zubkov explained. One possible connection is small vessel disease in the brain: tiny clots and damaged vessel walls can contribute to dementia, while increased platelet activity may play a role in that damage.

In people with a genetic tendency toward greater platelet activity, aspirin might reduce small vessel damage and chronic inflammation, Zubkov said. That is a proposed explanation for the observed association, not proof of the mechanism or evidence that aspirin treats dementia. The study looked at prevention, and it doesn’t show that aspirin can reverse or slow the disease once it develops.

The bleeding risk changes the calculation

Aspirin’s bleeding risks are well established. Regular use can cause internal bleeding, most often in the stomach and, more rarely, in the brain. In the subgroup that appeared to have fewer dementia cases, major bleeding also occurred at about twice the rate.

Bleeding risk can rise with age and with a history of ulcers or gastrointestinal bleeding, kidney disease, uncontrolled blood pressure, or heavy alcohol use. Other medications can add risk, including blood thinners, nonsteroidal anti-inflammatory drugs such as ibuprofen or naproxen, SSRIs, and steroids, Sorrell said.

Sorrell noted that current U.S. Preventive Services Task Force guidance recommends against starting low-dose aspirin for primary prevention in adults 60 and older because bleeding risks offset the expected benefit. He said this study doesn’t change that guidance. People already prescribed aspirin after a cardiac event shouldn’t stop taking it based on this finding without speaking with their doctor.

Established prevention measures remain the practical focus

The 2024 Lancet Commission on dementia prevention estimated that nearly half of dementia cases are linked to 14 modifiable risk factors, Zubkov said. Practical steps include managing high blood pressure and LDL cholesterol, getting regular physical activity, addressing hearing and vision problems, and sleeping sufficiently.

Other steps include limiting smoking and alcohol, seeking mental health care, maintaining social connections, and protecting against head injury. Zubkov said these measures have evidence behind them today, while research into genetic profiles may eventually help tailor prevention to individuals.

A finding to follow, not a reason to self-prescribe

The analysis points to a limitation of treating everyone as though they respond to medication in the same way. A drug with no apparent benefit across a whole trial may still warrant closer study in a genetically defined subgroup. But the aspirin result carries a substantial complication: the apparent reduction in dementia risk came alongside more major bleeding in that same group.

Sorrell called the study a proof of concept for precision prevention, while stressing that the finding needs replication and a dedicated trial before it changes care. The next meaningful step is to establish whether the subgroup result holds up and whether researchers can identify people for whom the benefit outweighs the harm. Until then, the study offers a research direction—not a new reason to begin daily aspirin.