5 min read
Key Points
Scientists discovered low-dose aspirin may reduce dementia risk in some people with a certain genetic profile.The same people also experienced a higher risk of bleeding on the drug.Doctors explain the takeaway for the general population.
As healthcare rapidly advances, doctors and scientists are leaning into the idea that a person’s genetic makeup shapes how they respond (or don’t respond) to medical treatment. It’s becoming increasingly clear that the treatment and prevention of conditions like cancer and dementia are not always a one-size-fits-all.
Here’s an example: For years, researchers had been looking at aspirin use as a way to help prevent dementia—after all, aspirin is an anti-inflammatory, and inflammation is thought to be a big driver in the development of Alzheimer’s disease. But when researchers in the 2018 ASPREE trial looked at the health effects associated with taking a low dose (100 milligrams) of aspirin daily in healthy older adults versus a placebo, they found that the drug had no significant benefit on the prevention of dementia. Two years later, another study using ASPREE data seemed to confirm this, finding that low-dose aspirin didn’t significantly reduce the risk of 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.
But more recently, different researchers took a closer look at the data, digging into it from a genetic standpoint. They found a potential benefit to the low-dose aspirin—just with a catch.
What did the study find?
The new study, which was published in Alzheimer’s & Dementia, looked at the polygenic scores (DNA scans that estimate genetic predisposition to disease) and genetic makeups of around 5,000 participants from the ASPREE trial. The people with scores that predicted a likelihood of high platelets—which may make the blood overly sticky and clot-prone—saw benefit when taking low-dose aspirin for the prevention of dementia.
“People in the top 20% for a genetic score tied to platelet count had far fewer dementia cases on aspirin,” explains 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%.”
Still, the prevention strategy was not without risks: The same group that benefited from the aspirin also had about twice the rate of major bleeding from it, Dr. Zubkov says.
As for the other participants who didn’t fit in that specific genetic subtype? “For the other 80% of participants, aspirin showed no dementia benefit,” he says.
What the findings mean
First of all, it’s not really easy to know right away if these findings are applicable to you because they rely on genetic analysis, which isn’t yet commonplace. A high platelet-associated polygenic score—as used in the study—reflects a person’s genetic tendency for high platelets, not a measured value that you would get from a regular blood test, says Dr. Zubkov. “Someone in that group may have a perfectly normal platelet count on their labs,” adds Luke Sorrell, M.D., 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,” Dr. Sorrell continues. “Nobody should look at their last complete blood count and draw conclusions from this study.” Without the specialized genetic testing, you won’t know if you fall in the group that could benefit from the low-dose aspirin.
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Even so, genetic testing that includes polygenic scores is becoming more widely available, notes Dr. Sorrell, so it’s not far-fetched that your doctor could potentially offer something like it in the future, if they don’t already. But that doesn’t change the fact that these findings were based on a small subgroup pulled from existing research, and more research is needed to replicate them. “That’s realistically years away,” Dr. Sorrell adds. “I’d discourage people from running consumer DNA files through online calculators to self-diagnose.”
There are also the well-studied risks of internal bleeding associated with regular aspirin use—namely in the stomach and, rarely but seriously, 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 explains. “This study doesn’t change that.” (Of course, this doesn’t apply if you are already prescribed daily aspirin for treatment post-cardiac event; in that case, you shouldn’t stop taking it based on these findings or any others you might see without talking to your doctor.)
Risks of aspirin-associated bleeding rise with age, a history of ulcers or gastrointestinal bleeding, kidney disease, uncontrolled blood pressure, heavy alcohol use, and the use of other medications including blood thifnners, 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 could be linked
The findings indicate that dementia was potentially prevented in the high-platelet genetic group by taking aspirin—not that the disease was treated by the drug. The link between dementia prevention and aspirin for these folks likely lies in how platelets function, our experts say.
“Platelets help form clots, and they also release chemical signals which drive inflammation. Aspirin blocks platelet activation and lowers inflammation,” explains Dr. Zubkov. “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 2024 Lancet Commission on dementia prevention estimated that nearly half of dementia cases are linked to 14 modifiable factors, says Dr. Zubkov. So the following could help:
Managing high blood pressure and high LDL cholesterolGetting enough physical activity Treating hearing and vision issues Sleeping sufficiently Limiting smoking and alcohol consumptionReceiving mental health care and getting social connectionProtecting 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 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.”
At the moment, the findings are a signal, not a prescription. “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.