Non-steroidal anti-inflammatory drugs (NSAIDs) are a broad class of pain-relievers that includes ibuprofen, aspirin, and naproxen. NSAIDs work by decreasing the levels of pro-inflammatory hormones called prostaglandins. Interestingly, recent studies have found that NSAIDs may also be beneficial for reducing the risk of dementia. A 2015 meta-analysis found that short-term NSAID users had a 28% reduced incidence of Alzheimer’s disease, while long-term users had a 64% reduction. Notably, this effect was only significant in observational studies and not randomized controlled trials, so a conclusive link between NSAIDs and brain health remains elusive.
One possible mechanism for how NSAIDs could combat Alzheimer’s is by regulating inflammatory pathways outside of prostaglandins. Studies suggest that Alzheimer’s disease is closely linked to a complex inflammatory network called the NLRP3 inflammasome. If NSAIDs could inhibit this inflammasome, it may protect the brain from neurodegeneration.
In a study published last week in Nature Communications, researchers investigated whether a class of NSAIDs called fenamates could inhibit the NLRP3 inflammasome. Fenamate NSAIDs include mefanamic acid, a common medication used to treat menstrual pain. The researchers treated mouse cell cultures with fenmates and found that they selectively inhibited the NLRP3 inflammasome without interfering with other inflammatory pathways. The researchers then treated two animal models of Alzheimer’s disease (rats and mice) with mefanamic acid over an extended period of time. Memory tests administered to the rats showed reduced impairment when they were given the drug. Meanwhile, the mice’s brains showed that signs of neuroinflammation had been reduced to healthy levels.
A limitation of this study is that the NLRP3 inflammasome has still not been conclusively linked to Alzheimer’s in humans. It is also not clear how well these animal models simulate the neuroinflammatory aspects of the disease. Future studies will likely examine how fenamates and other NSAIDs affect inflammatory pathways in humans to determine their potential as therapy. If mefanamic acid is one day repurposed as an anti-dementia drug, it could avoid the lengthy pipeline for FDA approval and be available immediately to consumers.