Long-Term Use of NSAIDs Linked to Lower Dementia Risk

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) was tied to a decreased risk of dementia, data from the prospective Rotterdam Study showed.

Over an average follow-up of 14.5 years, use of NSAIDs for 24 months or longer was associated with a 12% lower risk of dementia compared with non-use (HR 0.88, 95% CI 0.84-0.91), reported M. Arfan Ikram, MD, PhD, of Erasmus University in Rotterdam, the Netherlands, and co-authors.

The cumulative dose of NSAIDs, however, was not associated with decreased dementia risk, Ikram and colleagues noted in the Journal of the American Geriatrics Society.

The findings could not be explained by the amyloid-lowering properties of specific NSAIDs, the researchers said. Associations were stronger for long-term use of NSAIDs without known effects on amyloid-beta (HR 0.79, 95% CI 0.74-0.85) compared with amyloid-lowering NSAIDs (HR 0.89, 95% CI 0.85-0.93).

For people who used NSAIDs for less than 1 month, dementia risk was slightly elevated (HR 1.04, 95% CI 1.02-1.07), as it was for people who used NSAIDs for 1 month to 24 months (HR 1.04, 95% CI 1.02-1.06).

The findings provide important insights into the relationship between inflammation and dementia risk, suggesting that prolonged, rather than intensive, exposure to anti-inflammatory medication may hold potential for dementia prevention, the researchers noted.

There’s a strong hypothesis that inflammation plays a role in the dementia process and in Alzheimer’s disease, Ikram pointed out.

“This evidence comes from genetic and animal model studies, as well as some limited studies in clinical patients,” he told MedPage Today.

“The idea is that low-grade inflammation contributes to brain damage — and may also be a result of brain damage due to other detrimental causes like amyloid deposition or arteriolosclerosis,” he said. “This may induce a vicious cycle of various pathological processes enhancing and maintaining each other.”

The Rotterdam Study findings “suggest the inflammatory process in dementia may be very low-grade and protracted over a long period of time,” especially since high doses of NSAIDs over a short time frame didn’t reduce dementia risk, Ikram observed. “This makes sense: dementia has a very long preclinical phase during which the pathology slowly accumulates,” he said.

Other studies have identified relationships between anti-inflammatory agents and dementia. A meta-analysis showed a decreased dementia risk with NSAIDs in observational studies, but clinical trials — which typically assess NSAID use over much shorter time frames — have not.

Ikram and colleagues followed 11,745 participants in the population-based Rotterdam Study who were dementia-free at baseline. More than half (59.5%) were women, and mean age was 66.

The researchers used pharmacy dispensing records to determine cumulative duration and dose of NSAIDs starting in 1991. They defined four categories of cumulative use: non-use, short-term use (under 1 month), intermediate-term use (1 to 24 months), and long-term use (over 24 months).

Models were adjusted for lifestyle factors, comorbidities, and co-medication use. The researchers repeated this analysis after stratifying NSAIDs by their previously established amyloid-beta-lowering properties.

The study’s main limitation was its observational nature, Ikram noted. “There is a reason why some individuals did versus did not take NSAIDs. These reasons may include arthritis, pain, or other inflammatory conditions,” he said.

“It is impossible to fully adjust for the effect of these other conditions,” he acknowledged. “If these other conditions are in any way linked to dementia, it may distort our findings. However, the fact that we found a lower risk of dementia in users compared to non-users indicates that any such distortion may have been limited.”

The findings are also insufficient to start advising people to take NSAIDs for dementia, Ikram emphasized.

“Further evidence from similar studies or clinical trials is needed, complemented with proper risk-benefit analyses and a proper assessment on how any use of NSAIDs may or may not outweigh side effects or impact on other bodily functions,” he noted.

Please enable JavaScript to view the

comments powered by Disqus.