Long-Term NSAID Use May Lower Dementia Risk
April 30, 2025
By Seema Gupta, MD, MSPH
Synopsis: In a prospective population-based study of nonsteroidal anti-inflammatory drugs, long-term use was associated with a reduced risk for dementia compared with short- and intermediate-term use.
Source: Vom Hofe I, Stricker BH, Ikram MK, et al. Long-term exposure to non-steroidal anti-inflammatory medication in relation to dementia risk. J Am Geriatr Soc. 2025; Mar 4. doi: 10.1111/jgs.19411. [Online ahead of print].
As a chronic condition, dementia bears a significant global public health burden. It is estimated that approximately 10% of the U.S. population aged 65 years and older has dementia, with a higher prevalence found in residents of nursing homes and residential care communities.1 Alzheimer’s disease (AD) is the most common cause of dementia, accounting for approximately 60% to 80% of all dementia cases. An estimated 7 million older adults in the United States have AD, a number that is expected to double by 2060.
In 2024, the cost of caring for dementia patients aged 65 years and older, including healthcare, long-term care and hospice services, was estimated to be $360 billion. Evidence demonstrates that inflammatory processes, as well as the accumulation of the protein Aβ outside neurons and twisted strands of the protein tau inside neurons, are central to the pathology.2
As one of the most widely prescribed medications, non-steroidal anti-inflammatory drugs (NSAIDs) commonly are used for relief of pain or inflammatory conditions. Prior epidemiologic studies have shown that NSAID use can offer a protective effect on the development of AD. Additionally, animal studies have demonstrated a reduction in the formation of Aβ plaques in the brains of mice that also were exposed to NSAIDs.3 However, other evidence suggests that there is no beneficial effect of NSAIDs on cognition or overall AD severity.4
In their study, Vom Hofe et al obtained data from an ongoing population-based cohort study conducted in the Netherlands to evaluate the effects of long-term and cumulative NSAID doses on the risk of developing dementia. Researchers included 11,745 dementia-free participants from the prospective population-based Rotterdam Study. Approximately 60% were female, and the mean age was 66 years. During an average follow-up period of 14.5 years, approximately 81% of the cohort used NSAIDs, which reflected 93,859 cumulative months of NSAID use. The final analysis was adjusted for age, sex, education, lipid and liver enzyme profiles, lifestyle factors, comorbidity, and comedication use.
The study authors found that the risk for all-cause dementia was lower for long-term NSAID users (hazard ratio [HR] 95% confidence interval [CI], 0.88 [0.84-0.91]) and slightly higher for short-term NSAID users (HR 95% CI, 1.04 [1.02-1.07]) and intermediate-term NSAID users (HR, 1.04 [1.02-1.06]) when compared with nonusers. The cumulative NSAID dose was not associated with the risk for dementia.
Furthermore, protective effects were stronger with long-term use of non- Aβ-lowering NSAIDs (such as naproxen and rofecoxib) (HR 95% CI, 0.79 [0.74-0.85] than with Aβ-lowering NSAIDs (such as diclofenac and ibuprofen) (HR 95% CI, 0.89 [0.85-0.93]). The authors concluded that long-term NSAID use, but not cumulative dose, was associated with decreased dementia risk.
Commentary
Vom Hofe et al found that long-term use of NSAIDs was associated with a 12% reduced risk for dementia. Additionally, it seems that prolonged, rather than intensive, exposure to anti-inflammatory medications may hold the promise for dementia prevention. This finding may suggest that dementia may be the result of low-grade chronic inflammation and may respond to long-term use of NSAIDs.
However, because this was an observational study, it may be important to conduct further research with a prospective design to properly assess how any use of long-term NSAIDs may (or may not) outweigh side effects on other bodily functions. Therefore, while it may not yet be time to begin advising patients to take NSAIDs for dementia prevention, it is certainly some food for thought.
Seema Gupta, MD, MSPH, is Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV.
References
- Alzheimer’s Association. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19(4):1598-1695.
- Jorge L, Martins R, Canário N, et al. Investigating the spatial associations between amyloid-β deposition, grey matter volume, and neuroinflammation in Alzheimer’s disease. J Alzheimers Dis. 2021;80(1):113-132.
- Pasqualetti P, Bonomini C, Dal Forno G, et al. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease. Aging Clin Exp Res. 2009;21(2):102-110.
- Miguel-Álvarez M, Santos-Lozano A, Sanchis-Gomar F, et al. Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer’s disease: A systematic review and meta-analysis of treatment effect. Drugs Aging. 2015;32(2):139-147.
In a prospective population-based study of nonsteroidal anti-inflammatory drugs, long-term use was associated with a reduced risk for dementia compared with short- and intermediate-term use.
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