BERLIN — Do NSAIDs show promise in reducing the prevalence of dementia and Alzheimer’s disease in patients who use them? A new study says the answer is yes, especially with diclofenac and naproxen. Find out what differences were found and what the researchers believe to be the effects of NSAIDs on cognitive decline.
With dementia, especially Alzheimer’s disease (AD), expected to afflict 150 million people by 2050, researchers are constantly looking for pharmaceuticals that can help mitigate its effects. Those include progressive cognitive decline linked to neuroinflammation and neurodegeneration.
Previous studies which have examined nonsteroidal anti-inflammatory drugs (NSAIDs) as potential neuroprotective agents, particularly diclofenac, which has been proposed to modulate microglial inflammasome signaling. Those prior studies investigating NSAIDs in AD have yielded inconsistent findings, however. That led to the current effort to reexamine the relationship between selected NSAIDs and dementia outcomes in a large longitudinal cohort from the National Alzheimer’s Coordinating Center (NACC).
A team primarily from the United States but led by researchers from Charité Universitätsmedizin in Berlin analyzed cross-sectional and longitudinal data from the NACC database collected between 2005 and 2022, focusing on any associations between NSAID exposure and dementia, AD and cognitive trajectories. NSAID users with matched with nonusers while adjusting for demographic and clinical confounders. Researchers from the Dallas VAMC participated in the research.
Results published as a preprint in MedRXiv indicate that, among 47,165 participants, diclofenac and naproxen use were associated with a lower prevalence of dementia and AD compared with matched nonusers. Etodolac showed no significant associations, however.1
“Diclofenac users demonstrated reduced odds of dementia and AD,” the authors wrote. “Naproxen showed similar cross-sectional associations. In longitudinal modeling, diclofenac users had a significantly slower rate of cognitive decline than non-users.”
They add, “These findings suggest a compound-specific association between NSAID use and AD, with diclofenac potentially modulating disease progression through anti-inflammatory mechanisms. The observed modulation of longitudinal cognitive decline supports further investigation of inflammatory pathways, including microglial and inflammasome signaling, as therapeutic targets in biomarker-defined AD populations.”
- Hoehne CL, Salinas V, Shirani A, Stuve O, Stopschinski BE. NSAID use is associated with lower dementia and Alzheimer’s disease prevalence and slower cognitive decline: A retrospective longitudinal analysis of the NACC cohort. medRxiv [Preprint]. 2026 Jun 30:2026.06.27.26355593. doi: 10.64898/2026.06.27.26355593. PMID: 42428055; PMCID: PMC13345488.
