How Daily Pain Relievers Might Shield Your Brain from Dementia

In a world racing to find solutions for dementia, an answer might be hiding in medicine cabinets across the country. A large-scale Dutch study spanning nearly three decades has found that long-term use of common pain relievers could significantly reduce the risk of developing dementia—but only if taken consistently for more than two years.

The study, published March 4 in the Journal of the American Geriatrics Society, tracked over 11,700 initially dementia-free adults for an average of 14.5 years, providing one of the most comprehensive looks yet at how non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen might protect the aging brain.

Unlike previous shorter clinical trials that showed no benefit, this long-term observational study found that people who used NSAIDs for more than 24 months had a 12% lower risk of developing dementia compared to those who never used these medications.

“These findings provide important insight in the relationship between inflammation and dementia risk, and suggest that prolonged rather than intensive exposure to anti-inflammatory medication may hold potential for dementia prevention,” the researchers wrote in their paper.

The findings arrive at a critical moment. With dementia rates climbing worldwide and no effective preventative treatments available, identifying even modest protective factors could have massive public health implications. Currently, more than 55 million people worldwide live with dementia, a number projected to nearly triple by 2050.

What makes this study particularly valuable is its unprecedented scope. Using pharmacy dispensing records dating back to 1991, researchers from Erasmus Medical Center tracked exactly how long participants used NSAIDs and at what doses. During the follow-up period, 2,091 participants developed dementia, allowing researchers to identify patterns that shorter studies might miss.

Interestingly, the study found that the benefits weren’t linked to how much medication people took, but rather how long they took it. The cumulative dose made no difference in dementia risk, suggesting that consistent, long-term suppression of inflammation—rather than intensive short-term use—is what might protect the brain.

“Long-term NSAID use, but not cumulative dose, was associated with decreased dementia risk,” the researchers noted.

The association was even stronger for Alzheimer’s disease specifically, with long-term NSAID users showing a 21% reduced risk compared to non-users.

The study’s lead author, Ilse vom Hofe, and senior researcher, M. Arfan Ikram, explored multiple angles to understand the relationship. Previous laboratory research had suggested that some NSAIDs might help reduce the formation of amyloid-beta plaques—a hallmark of Alzheimer’s disease—in the brains of mice. However, when the team analyzed different types of NSAIDs, they found something surprising.

NSAIDs without known effects on amyloid-beta actually showed stronger protective effects than those known to reduce amyloid. This suggests that NSAIDs’ potential benefits go beyond targeting amyloid proteins and likely involve their fundamental anti-inflammatory properties.

The Rotterdam Study, as it’s known, tracked a predominantly white population in the Netherlands, which may limit how broadly the findings apply to more diverse populations. Additionally, the researchers couldn’t track over-the-counter NSAID use, meaning some participants classified as non-users might have been taking these medications without prescription.

Despite these limitations, the study provides compelling evidence that inflammation plays a crucial role in the development of dementia and that targeting it could be a viable prevention strategy.

While the results are promising, experts caution that NSAIDs come with significant side effects, especially when used long-term. These medications can cause gastrointestinal bleeding, kidney damage, and cardiovascular problems, particularly in older adults. In fact, NSAIDs are currently listed as “potentially inappropriate medications” for older adults according to the Beers criteria, a widely used set of guidelines for medication safety in geriatric care.

“Although our results are an indication of the important role of inflammation in the treatment of dementia, they do not justify the recommendation of long-term treatment with NSAIDs for the prevention of dementia, given its potential adverse effects,” the researchers cautioned.

The study also revealed an intriguing genetic angle. The protective effect of long-term NSAID use was only observed in people without the APOE-ε4 gene variant—the strongest known genetic risk factor for Alzheimer’s disease. For those carrying this variant, NSAIDs appeared to offer no protection, suggesting that different prevention strategies might be needed for different genetic profiles.

These findings add to a growing body of evidence linking inflammation to dementia. Previous research has shown that inflammatory processes play a central role in various pathologies underlying dementia, including vascular brain injury and the accumulation of toxic proteins. Indeed, approximately 20% of potential Alzheimer’s treatments currently in development target inflammation in some way.

As the global population ages, the race to find effective dementia prevention strategies becomes increasingly urgent. While this study doesn’t provide a simple answer, it does suggest that controlling chronic inflammation could be an important piece of the puzzle.

“Our results warrant further investigation on the potential of anti-inflammatory medication in the prevention of dementia,” the researchers concluded.

For now, experts emphasize that people should not start taking NSAIDs solely to prevent dementia. However, this research opens promising avenues for developing safer anti-inflammatory treatments specifically designed for long-term brain health, potentially addressing one of the most pressing health challenges of our time.