Research shows sustained NSAID use may shield the brain from dementia, particularly for individuals without a genetic predisposition—could your anti-inflammatory medication be key to healthy aging?
Study: Long-Term Exposure to Non-Steroidal Anti-Inflammatory Medication in Relation to Dementia Risk. Slladkaya / Shutterstock.com
A recent study published in the Journal of the American Geriatrics Society determines whether long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of developing dementia.
What causes dementia?
Dementia is characterized by a gradual decline in brain functioning. Inflammation is a common feature of various pathophysiological changes that contribute to the development of dementia, some of which include vascular brain injury and the accumulation of amyloid-β and tau proteins.
Hypertension, atherosclerosis, hypoperfusion, amyloid-β, and tau protein accumulation activate chronic neuroinflammatory responses, which subsequently increase the risk of dementia. Chronic neuroinflammation leads to greater vascular damage and amyloid-β and tau accumulation by inducing endothelial dysfunction and reducing the integrity of the blood-brain barrier (BBB).
NSAIDs and dementia risk
NSAIDs are anti-inflammatory analgesic agents that inhibit the enzymatic activity of cyclooxygenase 1 (COX-1) and COX-2. Previous in vivo studies have demonstrated that NSAID exposure may reduce amyloid-β plaque formation in the brains of mice.
Likewise, one meta-analysis revealed that, as compared to non-users, NSAID users were less likely to develop dementia. However, these findings were contradicted by another meta-analysis indicating no effect of NSAID use on dementia risk.
To date, few observational studies have evaluated the association between long-term NSAID use and dementia risk.
About the study
The current study obtained data from the Rotterdam Study, an ongoing population-based cohort study conducted in the Netherlands. These data were used to determine the effects of long-term and cumulative NSAID doses on dementia risks and how these medications may reduce the amyloid burden in the brain.
The Rotterdam Study began enrolling participants 55 and older in 1990. Compared to the beginning of the study, in which 7,983 individuals were enrolled, 14,926 individuals were ultimately included in the final study cohort. All participants undergo a follow-up examination at a dedicated research center every four years.
A total of 13,507 study participants were dementia-free at enrollment and provided informed consent for follow-up through medical records. At each date that a dementia diagnosis was reported, a sub-cohort consisting of dementia-free individuals who were matched on age and sex at that time point was created.
Study findings
At baseline, the mean age of the study participants was 66.2 years, 59.5% female. During the follow-up period, approximately 81% of the cohort used NSAIDs, which reflected 93,859 cumulative months of NSAID use.
Long-term use of NSAIDs was more frequently reported in females than males. As compared to short-term users, long-term NSAID users were more likely to have greater body mass index (BMI) values and be diagnosed with diabetes.
About 30%, 5.8%, and 45.6% of the cohort used NSAIDs with Aβ42-lowering properties, non-Aβ42-lowering NSAIDs, and both, respectively. Approximately 17.8% of the study participants were diagnosed with dementia after a mean follow-up period of 14.5 years. Notably, 73.4% of study participants diagnosed with dementia were diagnosed with clinical AD.
As compared to non-NSAID users, short- and intermediate-term use of NSAIDs was associated with an increased risk of all-cause dementia. However, long-term NSAID users who used these medications for over two years were less likely to be diagnosed with dementia. Cumulative NSAID doses were not associated with dementia risk.
Sensitivity analysis revealed that less than 24 months of NSAID use reduces the risk of developing dementia, whereas 12-24 months of NSAID use was associated with a marginal increase in dementia risk. As compared to Aβ42-lowering NSAIDs, non-Aβ42-lowering NSAIDs were more effective in reducing all-cause dementia and clinical AD risk.
The effects of long-term NSAID use in reducing the risk of all-cause dementia were only observed in participants lacking the apolipoprotein ε4 (APOE-ε4) allele but not those with the APOE-ε4 allele. Prolonged acetylsalicylic acid use did not impact dementia risk.
Conclusions
Long-term use of NSAIDs, but not short-term use, reduced the risk of developing dementia. Importantly, this beneficial effect was dependent on the duration of use and not on the cumulative dose.
The study findings indicate that the prolonged use of anti-inflammatory medications could prevent the onset of dementia. Nevertheless, additional research is needed to evaluate the potential of anti-inflammatory medications in preventing dementia.
Long-term inhibition of detrimental inflammatory processes, rather than exposure to a high cumulative dose, is more effective in the prevention of dementia.”
Journal reference:
- Stricker, B. H., Ikram, M. K., Wolters, F. J., & Ikram, M. A. (2025) Long-Term Exposure to Non-Steroidal Anti-Inflammatory Medication in Relation to Dementia Risk. Journal of the American Geriatrics Society. doi:10.1111/jgs.19411