Should You Take Aspirin to Prevent Dementia?

Daily low-dose aspirin did not lower dementia risk in a randomized trial of more than 19,000 older adults. A new analysis of that same trial, published in September in Alzheimer’s & Dementia by Dr. Peter Fransquet and colleagues at Monash University, looked at participants’ genetics and found one group of people who had fewer dementia cases on aspirin than on placebo. Platelets are small cell fragments in the blood that form clots, carry most of the blood’s supply of the protein that forms Alzheimer’s amyloid plaques, and lose much of their ability to clump when a person takes aspirin.

In people whose genes predict a high platelet count, the dementia rate on placebo was about 3.5 times the rate on aspirin. Major bleeds were also more common on aspirin, though the absolute increase was small. In the high-platelet group the increase was about 2 percentage points, from 2.1% to 4.4%. The same trial linked aspirin to higher cancer mortality, possibly by speeding up cancers people already had, so cancer screening matters for anyone considering aspirin, which a later section covers.

A large trial found no overall dementia benefit from daily aspirin in older adults.

The original trial. The ASPREE trial (Aspirin in Reducing Events in the Elderly) enrolled 19,114 healthy adults in Australia and the United States between 2010 and 2014. Participants were 70 or older, or 65 or older for Black and Hispanic participants in the US, and none had dementia or heart disease when they joined. Half took 100 mg of enteric-coated aspirin each day and half took a placebo. Participants were followed for a median of 4.7 years.

The dementia result. In the 2020 dementia report led by Dr. Joanne Ryan, rates of dementia were similar in the aspirin and placebo groups. Rates of mild cognitive impairment, an earlier stage of memory and thinking decline, were also similar and cognitive test scores changed at the same pace in both groups.

Bleeding. In the main trial report, major bleeding occurred in 3.8% of people on aspirin compared with 2.8% on placebo. Based on these results across all participants, the new study’s authors note that aspirin is not currently recommended for dementia prevention. This study explored whether it might be for people with a certain genetic makeup that results in higher platelets.

The new analysis tested whether a person’s genetics changed how aspirin affected dementia risk.

What a polygenic score is. Many traits, such as height or the number of platelets in the blood, are shaped by thousands of small genetic differences that each have a tiny effect. A polygenic score adds up those small effects into one number that estimates where a person is likely to fall for that trait. Researchers have published thousands of these scores in a public research database called the PGS Catalog.

How the screen worked. The Monash team had genetic data for 13,541 ASPREE participants and calculated 5,182 polygenic scores for each person. They then tested whether any score changed aspirin’s effect on dementia or on major bleeding. Testing thousands of scores turns up some findings by chance, so the team applied a statistical correction for the number of tests.

What passed the correction. Three platelet-count scores passed. The three are highly correlated, which means they rank people in a similar order. Among all the scores that showed a possible aspirin effect before the correction, platelet-related scores also appeared more often than would be expected by chance.

People with the highest platelet-count genetic scores had fewer dementia cases on aspirin.

The 3.5X figure. The team split participants into five equal groups based on one of the platelet scores. In the fifth with the highest scores, the dementia rate on placebo was about 3.5 times the rate on aspirin. Put the other way, people in this group who took aspirin had a 72% lower rate of dementia than those who took placebo. In the other four-fifths of participants, dementia rates on aspirin and placebo were similar.

Major bleeding in the same group. About 44 of every 1,000 people in the high-score group had a major bleed on aspirin, compared with about 21 of every 1,000 on placebo. That is about twice the rate, or about 23 additional major bleeds for every 1,000 people who took aspirin. The authors write that the lower dementia risk in this group has to be weighed against the higher bleeding risk.

Alzheimer’s risk genes did not change aspirin’s effect. The team also tested APOE, a gene with a well-studied effect on Alzheimer’s risk, along with polygenic scores built to predict dementia and Alzheimer’s disease. None of these changed aspirin’s effect on dementia. The authors interpret this as pointing to platelet biology as the source of the aspirin signal.

The study grouped people by a genetic score that predicts platelet count.

Genes and measured counts. The platelet count on a routine blood test depends on genetics and also on factors such as inflammation and iron levels. A polygenic score captures only the inherited part of that variation. The analysis used only the genetic score, so it could not test whether a high measured platelet count on a routine blood test would identify the same people who appeared to benefit.

Why measured platelets were not available. The paper reports that measured platelet count, platelet clumping, and platelet activation were not available in the ASPREE trial. Routine blood counts were added to the annual laboratory tests only during the later ASPREE-XT follow-up, after participants had stopped the study pills. Those later counts cannot be paired with the period when people were randomly assigned to aspirin or placebo.

Why the team used genetics. DNA was collected when participants joined the trial and was later genotyped. This allowed the team to test every score in the PGS Catalog against aspirin’s effect without choosing a hypothesis in advance. The platelet finding came from that screen. A person’s genetic score is also fixed from birth, so illness or medications during a trial do not change it.

A check the team could run for triglycerides. In the companion triglyceride analysis, the team had blood triglyceride measurements from the start of the trial. Those measured levels showed a pattern similar to the genetic score. No equivalent check was possible for platelets. The authors describe the platelet findings as a hypothesis that needs to be tested and call for studies that combine genetic risk with measured platelet function.

Platelets and dementia risk without aspirin. The authors also raise the possibility that a genetically higher platelet count may itself be linked to higher dementia risk, independent of aspirin. The platelet score on its own did not predict dementia across the full group or in the placebo group. The authors suggest that any relationship between genetically predicted platelet count and dementia may not rise steadily as the score rises.

Platelets can be measured with a routine blood count and with specialized tests of how they work.

Platelet count. A complete blood count, often called a CBC, is a routine blood test that reports the number of platelets in a microliter of blood. A typical adult reference range is about 150,000 to 450,000 platelets per microliter, though each laboratory sets its own range. Most CBCs also report mean platelet volume, the average size of the platelets in the sample.

Platelet clumping. Specialized tests measure how readily platelets clump together. The standard laboratory method, light transmission aggregometry, measures how much light passes through a blood sample as platelets clump and the sample clears. Some point-of-care devices measure how strongly aspirin is blocking platelet activity. A urine test for a breakdown product of thromboxane, a clotting signal made by platelets, also reflects aspirin’s effect.

Platelet activation. Research laboratories can measure how activated platelets are using flow cytometry, a method that tags proteins on the surface of individual cells and counts them. These tests are used mainly in research.

The genetic score. The score in this study is calculated from DNA in a blood or saliva sample. The DNA is read on a genotyping array. Software then adds up the score’s genetic variants, each weighted by how strongly it relates to platelet count in large genetic studies. This score is not part of a CBC.

Platelets carry most of the amyloid precursor protein found in the blood.

How aspirin affects platelets. Platelets are small cell fragments in the blood that clump together to form clots. Low-dose aspirin permanently blocks an enzyme in platelets called COX-1, which reduces each platelet’s ability to clump for the rest of its lifespan of about a week to ten days.

Platelets and amyloid. Amyloid beta, the protein that builds up into plaques in the brains of people with Alzheimer’s disease, is produced when enzymes cleave a larger protein called amyloid precursor protein. In 1990, researchers showed that human platelets release amyloid precursor protein when they are activated. A 1994 study found that people with a rare inherited platelet disorder had less of this protein in their platelets and also lower levels in their blood plasma, which pointed to platelets as the main source of the protein in plasma.

A proposed mechanism. Dr. Fransquet has described the connection between platelet biology and dementia risk as a proposed mechanism that has not yet been proven.

Aspirin was linked to higher cancer mortality in the same trial of older adults.

Overall mortality. A separate ASPREE report found all-cause mortality was 14% higher on aspirin over a median of 4.7 years, with cancer mortality accounting for most of the difference. Cancer mortality occurred in 3.1% of people on aspirin and 2.3% on placebo.

The number of new cancers was the same. A 2020 cancer analysis of ASPREE led by Dr. John McNeil found that aspirin did not change how many people were diagnosed with cancer. People on aspirin were 19% more likely to have a cancer that had already spread when it was diagnosed and 22% more likely to be diagnosed at stage 4.

A possible explanation. People with a history of cancer were allowed to join ASPREE. The authors of the 2020 analysis suggested that in older adults aspirin may speed up the progression of cancers that have already developed, including cancers that had not yet been diagnosed when people started taking it. How aspirin would do this has not been shown.

Younger adults. Earlier studies, mostly in middle-aged adults, reported that aspirin lowers cancer risk after about 10 years of use, particularly for colorectal cancer. ASPREE started aspirin at age 70 or older and lasted under five years.

Longer follow-up. A 2026 follow-up in JAMA Oncology tracked participants for a median of 8.6 years. Aspirin again did not change how many people developed cancer, including colorectal cancer. Cancer-related mortality was 15% higher overall in people originally assigned to aspirin. The authors found no excess cancer mortality in the years after people stopped taking the study pills.

Cancer screening. Since the higher cancer mortality appears tied to cancers already present when people started aspirin, I recommend that anyone considering aspirin for dementia prevention be up to date on enhanced cancer screening best practices first.

Several features of the study limit what it can show at this stage.

An analysis after the fact. ASPREE was designed to test whether aspirin extended healthy, disability-free life and the genetic analysis was carried out years after the trial ended. Subgroup findings from this kind of search need to be confirmed in a separate group of people before they can guide treatment.

The size of the subgroup. The high-score group was one-fifth of 13,541 people, or roughly 2,700, split between aspirin and placebo. Because the number of dementia cases in that group was small, the range of plausible values for aspirin’s effect is wide, from a 48% to an 85% lower dementia rate.

Who was in the trial. Participants were healthy adults mostly aged 70 and older and 8.7% of the full ASPREE group were nonwhite. The results may not apply to younger adults or to more diverse populations.

No clinical test yet. The study does not provide a clinical test and the platelet score has not been validated for guiding decisions about aspirin.

What the authors advise. Dr. Fransquet has said people should not start aspirin to prevent dementia based on this study without consulting their doctor, given the higher risk of serious bleeding. The team describes the next steps as confirming the finding in other groups and working out the biology that connects platelets to aspirin’s effect on dementia.

The same research group has found a genetic score that changes aspirin’s effects on heart disease and bleeding.

A triglyceride score in the same trial. In a companion analysis of ASPREE published earlier this year in Clinical Pharmacology & Therapeutics, Dr. Fransquet and colleagues found that a genetic score for blood triglyceride levels changed how people responded to aspirin. In the lowest fifth of that score, the major bleeding rate on aspirin was about 2.3 times the placebo rate with no change in major cardiovascular events such as heart attack and stroke. In the highest fifth, aspirin was linked to a 34% lower rate of major cardiovascular events and a 38% lower rate of major bleeding. Triglyceride levels measured on a standard blood lipid panel at the start of the trial showed a similar pattern. People with lower triglycerides had more bleeding on aspirin without a cardiovascular benefit.

The next test. A randomized trial that enrolls people with high platelet genetic scores would show whether the lower dementia rate holds up in a new group and how it compares with the added bleeding risk.

My take

I will be looking at my own platelet count and my polygenic score for platelets and considering aspirin for dementia prevention myself.