Taking Pain Relief Drugs Long-Term May Lower Dementia Risk for Some People

People who take medications such as ibuprofen or aspirin long-term may be less likely to develop dementia, a new study found.

The research—published in the Journal of the American Geriatrics Society on March 4—found that taking prescription non-steroidal anti-inflammatory drugs (NSAIDs) regularly over a span of at least two years was linked to a 12% lower risk of dementia.

The results are likely explained by NSAIDs’ ability to quell people’s low-grade chronic inflammation, said lead study author Arfan Ikram, MD, PhD, professor and chair of the department of epidemiology at Erasmus University Medical Center.

A growing body of research, which includes both animal and human studies, suggests that long-term inflammation, particularly in the brain, can be one cause of dementia—a condition affecting millions of Americans.

“The idea is that low-grade inflammation contributes to brain damage,” Ikram told Health. Since dementia is a disease with a long onset period that’s well underway years before symptoms appear, “it makes sense that you can impact this process over a long period of time with small amounts of anti-inflammatory effect,” he explained.

However, this also means that people without underlying chronic inflammation issues likely won’t benefit from daily NSAID use, experts agreed.

For this study, Ikram and his team used data from nearly 12,000 people enrolled in a decades-long chronic disease study in Rotterdam, Netherlands.

The study participants had an average age of 66 and about 60% were female.

Researchers collected information about participants’ long-term NSAID use by looking at pharmacy dispensing records. This meant, however, that the study didn’t account for anyone regularly taking NSAIDs they bought over-the-counter, which is a limitation.

Based on the data they did have, Ikram and his team divided people into four groups: people who didn’t use NSAIDs, those who took NSAIDs daily for less than a month, those who took the medications daily for one to two years, and those who took them daily for more than two years. After that, they expanded the analysis to include a group that took NSAIDs daily for more than three years.

After 14 years of follow-up, about 2,100 participants (roughly 18%) developed dementia. Of those, 1,534 developed Alzheimer’s disease.

The results showed that, compared to the non-NSAID group, those who took the medications regularly for less than two years had a slightly increased dementia risk. But those who used NSAIDs for more than two years had a 12% reduction in dementia risk.

Interestingly, the dose a person took didn’t appear to have anything to do with their dementia risk. Instead, the effect appeared to be related to how long a person used the drugs.

“It wasn’t that they were taking higher or lower doses, but that they were taking it, which does speak to this idea of dampening inflammation,” said Nate Chin, MD, medical director for the Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention at the University of Wisconsin-Madison.

Despite mounting evidence of this connection between inflammation and dementia, many questions remain.

For one, it’s not totally clear how genetic risk might influence this relationship. In this study, people with the APOE-ε4 allele—a genetic predisposition to dementia—did not see lower rates of the disease if they took NSAIDs long-term.

“One of the thoughts of why these people have higher risk for dementia is that maybe they have higher inflammation,” Chin told Health. “But this study didn’t show this.”

Also, the study was observational, which means the findings should be taken with a grain of salt. This type of research cannot show a direct cause-and-effect. It just shows that long-term NSAID use and dementia risk are connected to one another.

Researchers have been studying the potential link between NSAID use and dementia for decades.

So far, the existing studies “aren’t all consistent, but a large number of them do show that people who are habitual NSAID users seem to have less Alzheimer’s disease,” John Breitner, MD, MPH, Alzheimer’s disease researcher and professor Emeritus of psychiatry at McGill University, told Health.

But understanding why, and who might benefit, is where things get complicated.

“The real question becomes, if you take people who aren’t in need of NSAIDs and you give them NSAIDs—or for that matter, any number of anti-inflammatory drugs—will they reduce their risk of Alzheimer’s disease?” Breitner said. “The answer is uniformly negative.”

Ikram and his colleagues echoed this sentiment as well, stressing that people who do not already need to take NSAIDs to treat an existing condition should not start now in an effort to protect their brain health.

“The researchers of this study are not arguing for people to take more NSAIDs, [but] rather that inflammation appears to be connected to dementia,” Chin added.

Not only is this because healthy people likely won’t see any brain health benefits from taking NSAIDs, but also because long-term NSAID use can raise the risk of other health issues. These include stomach inflammation, increased risk of heart attack and stroke, high blood pressure, and kidney damage, said Chin. Greater risk of brain bleeds is also a concern.

“They are not harmless drugs,” he said.

But for those in need of anti-inflammatory drugs—including people with chronic pain or diseases such as rheumatoid arthritis—tamping down widespread inflammation in the body appears to be good for cognitive health.

In addition to Ikram’s research, a 2022 study of people with rheumatoid arthritis found that those who took hydroxychloroquine, which has anti-inflammatory properties, had lower rates of dementia and Alzheimer’s disease than those who didn’t take the drug.

“We aren’t saying NSAIDs are the answer,” Chin added. “What we are saying is that inflammation could be the process that our bodies are going through that is leading to dementia.”