Common OTC Drug Tied to Much Lower Dementia Risk, but Only for a Specific Genetic Group

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As medicine continues to advance, researchers and clinicians are increasingly focused on how a person’s genetics can influence the way they respond to treatment. It is becoming clearer that preventing and treating conditions such as cancer and dementia is not always a one-size-fits-all process.

Aspirin has long been studied as a possible way to help ward off dementia. Because it is an anti-inflammatory drug, scientists have thought it might help address inflammation, which is believed to play a major role in Alzheimer’s disease. Yet when researchers in the ASPREE trial examined the effects of taking 100 milligrams of aspirin daily in healthy older adults, they found no meaningful dementia-prevention benefit compared with placebo. A later analysis of ASPREE data came to a similar conclusion, showing that low-dose aspirin did not significantly lower the risk of Alzheimer’s disease, dementia, mild cognitive impairment, or cognitive decline.

More recently, however, another team took a genetic look at the same data and found a possible benefit from low-dose aspirin, though only under a particular condition.

What did the study find?

The new study, published in Alzheimer’s & Dementia, examined polygenic scores and genetic profiles from about 5,000 participants in the ASPREE trial. Participants whose scores suggested a tendency toward high platelets—something that may make blood more sticky and prone to clotting—appeared to benefit from low-dose aspirin when it came to preventing dementia.

“People in the top 20% for a genetic score tied to platelet count had far fewer dementia cases on aspirin,” says Alexander Zubkov, M.D., a board-certified neurologist and physician with 1MD Nutrition. “About 1% of them developed dementia on aspirin, compared with 3.3% on placebo. In relative terms, their [relative] risk dropped by roughly 70%.”

That said, the same subgroup also experienced about twice as much major bleeding while taking aspirin, Zubkov notes.

For everyone outside that genetic category, the drug did not appear to help. “For the other 80% of participants, aspirin showed no dementia benefit,” he says.

What the findings mean

It is not easy to know whether these results apply to you, because they depend on genetic analysis that is not yet widely available. The high platelet-associated polygenic score used in the study reflects a genetic tendency toward higher platelet count, not a measurement from a standard blood test, Zubkov says. “Someone in that group may have a perfectly normal platelet count on their labs,” adds Luke Sorrell, M.D., a board-certified internist in longevity medicine and founder of Sorrell MD.

“Conversely, a high platelet count on routine bloodwork usually reflects something temporary, like iron deficiency, inflammation, infection, or recovery from surgery,” Sorrell says. “Nobody should look at their last complete blood count and draw conclusions from this study.” Without specialized genetic testing, there is no way to know whether you fall into the group that may benefit from low-dose aspirin.

Even so, Sorrell points out that polygenic testing is becoming more accessible and may eventually be offered more routinely. Still, these findings came from a small subgroup within existing research, and more work is needed to confirm them. “That’s realistically years away,” he says. “I’d discourage people from running consumer DNA files through online calculators to self-diagnose.”

There are also well-established bleeding risks linked to regular aspirin use, especially in the stomach and, more rarely, in the brain. “Current U.S. Preventive Services Task Force guidance recommends against starting low-dose aspirin for primary prevention in adults 60 and older because bleeding risk offsets the benefit,” Sorrell explains. “This study doesn’t change that.” This does not apply to people already prescribed daily aspirin after a cardiac event; they should not stop taking it without speaking to their doctor.

Bleeding risks rise with age, a history of ulcers or gastrointestinal bleeding, kidney disease, uncontrolled blood pressure, heavy alcohol use, and the use of other medications such as blood thinners, NSAIDs like ibuprofen or naproxen, SSRIs, or steroids, Sorrell says. “The key point in this study is that bleeding roughly doubled in exactly the group that appeared to benefit,” he says. “That trade-off is the whole story.”

How aspirin and dementia could be linked

The results suggest that aspirin may have helped prevent dementia in the high-platelet genetic group; they do not show that the drug treats dementia. Experts say the possible connection likely lies in the way platelets work.

“Platelets help form clots, and they also release chemical signals which drive inflammation. Aspirin blocks platelet activation and lowers inflammation,” Zubkov explains. “Small vessel disease in the brain caused by tiny clots and damaged vessel walls contributes to a large share of dementia cases. In people with a genetic tendency toward more platelet activity, aspirin might reduce this small vessel damage and the chronic inflammation behind it.”

How to lower dementia risk

The Lancet Commission on dementia prevention estimated that nearly half of dementia cases are linked to 14 modifiable factors, Zubkov says. Helpful steps include:

• Managing high blood pressure and high LDL cholesterol

• Getting enough physical activity

• Treating hearing and vision issues

• Sleeping sufficiently

• Limiting smoking and alcohol consumption

• Receiving mental health care and getting social connection

• Protecting against head injury

“These steps have solid evidence behind them today, while research like this [new study] works toward more personalized options,” he notes.

The bottom line

“This study is an exciting proof of concept for precision prevention,” says Sorrell. “A drug that looks useless on average may help a specific, genetically identifiable group, and that is the direction longevity medicine is heading.”

For now, the findings should be viewed as a promising signal rather than a recommendation. “The benefit and the harm were essentially the same size in absolute terms, and the finding needs replication and a dedicated trial before it changes anyone’s care,” he concludes.