- Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of medications that people commonly use to help reduce pain and inflammation.
- Experts are interested in how NSAIDs may affect dementia risk.
- One study found that the use of NSAIDs for over 2 years was associated with a lower risk for dementia, while use for less time was associated with a slight increase in dementia risk.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are common medications, such as ibuprofen, that can help with pain, fevers, and inflammation.
While highly useful for symptom relief, experts are also interested in the potential long-term effects.
A study recently published in the
After analyzing data from 11,745 participants, the results indicated that the use of NSAIDs for longer than 2 years lowered the risk of dementia.
Shorter time frames were associated with a slight increase in risk for dementia. Researchers also found that the cumulative amount of NSAIDs did not decrease the risk for dementia.
This suggests that time of exposure matters regarding the potential benefits of NSAID use on dementia risk.
The authors of this study note that inflammation may be a critical piece in the development of dementia. NSAIDs help with inflammation and may affect dementia risk. This study sought to understand more about the long-term impact of NSAIDs on dementia risk.
Researchers used data from participants in the Rotterdam Study, a current prospective population-based study in The Netherlands.
For the current analysis, researchers included participants who did not have baseline dementia, including 11,745 participants in the final analysis based on all their criteria. The average age of participants was around 66 years old.
Researchers used pharmacy records to examine participants’ oral NSAID use. They also divided NSAIDs into two categories: beta-amyloid-42-lowering or non-beta-amyloid-42-lowering.
This distinction had to do with previous data on how certain NSAIDs may affect amyloid levels in the brain. Accumulation of beta-amyloid in the brain is related to increased dementia risk.
Participants underwent regular dementia screening. Researchers also had data on several Health indicators and lifestyle factors, including blood pressure, diabetes, cholesterol levels, body mass index, education level, and smoking habits.
Researchers divided participant NSAID use into four main categories:
- no use
- short-term use, which was less than 1 month
- intermediate-term use, which was 1 month to 2 years
- long-term use, which was more than 2 years.
Additional analyses used other time frames to allow for more assessment. Researchers used a few different models to look at the relationship between all-cause dementia and time of NSAID use and to account for different factors.
They further conducted several sensitivity analyses, such as looking at the relationship between NSAIDs and Alzheimer’s disease, and the association between dementia and salicylates, substances found in medications such as aspirin.
Researchers had an average follow-up time with participants of 14.5 years. During the follow-up, 81.3% of participants used NSAIDs.
Just under 6% of participants used only NSAIDs that did not have beta-amyloid-42-lowering properties, and about 46% used a combination of non-beta-amyloid-42-lowering and beta-amyloid-42-lowering NSAIDs.
A little over 2,000 participants developed dementia.
Short-term and intermediate-term use of NSAIDs slightly increased the risk for all-cause dementia, while long-term NSAID use decreased the risk.
The association between long-term NSAID use and reduced risk for Alzheimer’s disease was even stronger than for all-cause dementia.
They also found that non-beta-amyloid-42-lowering NSAIDs appeared to lower the risk for all-cause dementia more than beta-amyloid-42-lowering NSAIDs.
Researchers did not find an association between cumulative NSAID dose and dementia risk reduction. They also found that NSAIDs did not appear to lower the risk for all-cause dementia among participants who had the APOE-e4 allele.
The
Vernon Williams, MD, a sports neurologist and founding director of the Center for Sports Neurology and Pain Medicine at Cedars-Sinai Orthopaedics in Los Angeles, who was not involved in this research, commented with his thoughts on the study to Medical News Today.
He told us:
“I think it’s very interesting in that it is another piece of evidence that will hopefully contribute to our understanding of dementia and opportunities to reduce risk. There are some limitations to an observational study like this, but overall, it seems to be in line with other evidence and past studies that suggest inflammation as having a key role in neurodegeneration […] It further contributes to the understanding of chronic inflammation as a target for additional study and intervention.”
This study does have some limitations. This study only included individuals from The Netherlands, and most participants were white, so the results cannot be generalized to all people.
There was some missing data for participants, and some information, such as alcohol use, was self-reported. The study also cannot establish cause.
This study was also able to only look at prescription use of NSAIDs, even though NSAIDs are also available over the counter. It’s possible that some participants who researchers noted not to be taking NSAIDs were doing so.
When it came to the diagnosis of Alzheimer’s, researchers could not include biomarkers, so misclassification is possible. It is also possible that participants who used NSAIDs long-term were healthier than participants who only used NSAIDs in the short term.
Researchers did account for the use of aspirin in one of the models. They did not categorize aspirin as an NSAID. When analyzing aspirin separately, they did not find an association between long-term use and reduced dementia risk.
The authors note that with the slight increase in risk for all-cause dementia from short-term and intermediate-term use, the “effect estimates were too small to obtain clinical relevance.”
Furthermore, the researchers also acknowledge that looking at all-cause dementia includes dementia subtypes where NSAIDs may have no impact. Thus, if these subtypes are included in the analysis, it is possible to have weakened effect estimates.
Finally, it is also possible that researchers did not account for certain relevant factors or that participants were not taking prescribed medication.
Speaking to MNT, study author Mohammad Arfan Ikram, MD, PhD, professor of epidemiology at the Erasmus University Medical Center in The Netherlands, further noted several limitations of their work:
“[The] main limitation of this study is that it is an observational study, in which persons were not randomized. In other words, there is a reason why these individuals did versus did not take NSAIDs. These reasons may include arthritis, pain, or other inflammatory conditions. It is impossible in such studies to fully adjust for the effect of these other conditions. If these other conditions are in any way linked to dementia, it may then distort our findings.”
Overall, this research highlights a potential benefit of NSAID use in the long term. This research could also help with creating therapeutics that protect against dementia.
Williams noted that “the study suggests that exposure to anti-inflammatories over time may be of potential benefit.”
“However,” he cautioned, “there are potential side effects and risks associated with currently available NSAIDs. The findings that the association was stronger for non-amyloid lowering NSAIDs compared to those with known amyloid lowering properties is interesting in that it implies the mechanism of action may not be entirely related to amyloid reduction. So other anti-inflammatory pathways and/or genetic risk factor effects may be contributing to the benefits. “
More research is likely needed before there are major changes to clinical recommendations. The study itself also notes that it may be inappropriate for older adults to use NSAIDs.
Ikram noted:
“Our findings alone are insufficient to start advising people to take NSAIDs for dementia. Further evidence from similar studies or [randomized controlled trials] is needed, complemented with proper risk-benefit analyses and also a proper assessment how any use of NSAIDs may or may not outweigh side-effects or impact on other bodily functions.”
