A Familiar OTC Medicine Could Cut Dementia Risk by 70%—With a Major Trade-Off

Researchers have found that low-dose aspirin may lower dementia risk in certain people with a specific genetic profile, but the same group also appears to face a higher bleeding risk while taking it.

As medicine becomes more personalized, doctors are increasingly recognizing that genes can influence how well a treatment works. That is especially true for conditions such as cancer and dementia, where prevention and care are not always effective in the same way for everyone.

Aspirin has long been studied as a possible way to help prevent dementia. Because it reduces inflammation, scientists thought it might help with Alzheimer’s disease, which is also linked to inflammatory processes. Yet when researchers analyzed data from the ASPREE trial, which tested 100 milligrams of aspirin daily in healthy older adults, they found no meaningful reduction in dementia. A later study based on the same data reached a similar conclusion, showing no significant drop in Alzheimer’s, dementia, mild cognitive impairment, or cognitive decline.

Meet the experts: Luke Sorrell, M.D., board-certified internist in longevity medicine and founder of Sorrell MD; and Alexander Zubkov, M.D., board-certified neurologist and physician with 1MD Nutrition.

More recent research took a different approach by examining the data through a genetic lens. That analysis suggested a possible benefit from low-dose aspirin, though only for a narrow group of people.

What the study found

The study, published in Alzheimer’s & Dementia, examined polygenic scores and genetic profiles from about 5,000 participants in the ASPREE trial. People whose scores suggested a tendency toward higher platelet levels, which can make blood more prone to clotting, appeared to benefit from low-dose aspirin when it came to dementia prevention.

“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. “About 1% of them developed dementia on aspirin, compared with 3.3% on placebo. In relative terms, their risk dropped by roughly 70%.”

But the potential upside came with a downside: the same group also had about twice the rate of major bleeding while taking aspirin, Dr. Zubkov says.

For participants who did not match that genetic subtype, aspirin 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 for most people to know whether these results apply to them, because the study depended on genetic testing that is not yet routine. The high platelet-associated polygenic score used in the research reflects inherited risk, not a value you would see on a standard blood test, Dr. Zubkov explains. “Someone in that group may have a perfectly normal platelet count on their labs,” adds Luke Sorrell, M.D.

Dr. Sorrell also notes that an elevated platelet count on routine bloodwork usually points to something temporary, such as iron deficiency, inflammation, infection, or recovery from surgery. “Nobody should look at their last complete blood count and draw conclusions from this study,” he says. Without specialized genetic testing, there is no way to know whether someone belongs to the subgroup that may benefit.

Genetic testing that includes polygenic scores is becoming more widely available, Dr. Sorrell says, so doctors may eventually have access to tools like this more often. Even so, the findings came from a small subgroup within existing research and still need to be confirmed. “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, 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,” Dr. Sorrell says. “This study doesn’t change that.” People who already take daily aspirin after a cardiac event should not stop it based on this research alone and should speak with their doctor first.

Bleeding risk rises with age, a history of ulcers or gastrointestinal bleeding, kidney disease, uncontrolled blood pressure, heavy alcohol use, and use of other medications such as blood thinners, NSAIDs like ibuprofen or naproxen, SSRIs, or steroids, Dr. Sorrell explains. “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 may be connected

The study suggests that aspirin may have helped prevent dementia in the high-platelet genetic group rather than treating dementia after it developed. Experts say the link likely has to do with platelet function.

“Platelets help form clots, and they also release chemical signals which drive inflammation. Aspirin blocks platelet activation and lowers inflammation,” Dr. 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.”

Ways to reduce dementia risk

Dr. Zubkov says the latest Lancet Commission on dementia prevention estimated that nearly half of dementia cases are linked to 14 modifiable factors. Steps that may help include:

• Managing high blood pressure and high LDL cholesterol
• Getting enough physical activity
• Treating hearing and vision problems
• Sleeping enough
• Limiting smoking and alcohol use
• Seeking mental health care and staying socially connected
• Protecting against head injury

“These steps have solid evidence behind them today, while research like this works toward more personalized options,” he says.

The takeaway

“This study is an exciting proof of concept for precision prevention,” says Dr. 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 results are best viewed as an important clue rather than a new 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 says.