A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease
Abstract
Background and aims Epidemiological studies have examined the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Alzheimer's disease (AD). Recently, a variety of experimental studies indicates that a subset of NSAIDs, such as ibuprofen or flurbiprofen, also have Abeta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. In this trial, we evaluated whether the non-selective NSAID ibuprofen slows disease progression in patients with mild to moderate AD.Methods This was a 12-month multicenter, randomized, double-blind, placebo-controlled, parallel group trial. Participants with mild-moderate AD (Mini-Mental State Examination score >15, <26; Clinical Dementia Rating= 0.5-1), 65 years or older, with reliable caregivers, were recruited between April 2003 and September 2004. Seven AD Outpatient Treatment Centers screened 530 patients, 132 of whom were enrolled. Intervention consisted of 400 mg ibuprofen twice a day or placebo, together with 20 mg once a day of esomeprazol, or placebo. The primary measure was any one-year change in the Alzheimer Disease Assessment Scale- Cognitive (ADAS-Cog) subscale score. Secondary measures included changes in MMSE, CDR, Basic and Instrumental Activities of Daily Living scales, and Neuropsychiatric Inventory (NPI).Results Fifty-one patients (77%) in the ibuprofen vs 46 (70%) in the placebo group completed the protocol (p>0.20). In intention-to- treat analysis, ADAS-Cog score worsening was similar in the two groups (p=0.951, treatment difference= 0.1, CI -2.7; 2.9). No differences were found for any secondary outcomes. In a subsample of genotyped patients, ApoE epsilon4 carriers treated with ibuprofen (n=27) were the only group without significant cognitive decline.Conclusions Ibuprofen, if used for relatively short periods of time and although well tolerated thanks to gastroprotection, does not seem to be effective in tertiary prevention of mild-moderate AD. Our results suggest the need to examine whether differences in the response to NSAIDs exist, based on ApoE epsilon4 carrier status.
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Clinical trials targeting inflammation with NSAIDs have not improved cognition in AD patients.
“Unexpectedly, clinical trials targeting inflammation with NSAIDs have not improved cognition in AD patients [111, 112].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [111]
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- Authors
- Pasqualetti, P., Bonomini, C., Dal Forno, G., Paulon, L., Sinforiani, E., Marra, C., Zanetti, O., & Maria Rossini, P.
- Affiliations
- Centro San Giovanni di Dio Fatebenefratelli (IT)
- Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT)
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Zanetti, Orazio
- ORCID
- Venue
- Aging Clinical and Experimental Research
- Published
- 2009-04
- Volume
- 21
- Issue
- 2
- Pages
- 102-110
- ISSN
- 1594-0667 (ISSN-L)
- 1720-8319
- OpenAlex
- W1967583546
- Cited by
- 172
- References
- 61
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 9 · 2023: 12 · 2022: 13 · 2021: 11 · 2020: 14 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 13 · 2015: 9 · 2014: 9 · 2013: 6 · 2012: 13
- FWCI
- 9.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Aging Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- ibuprofen, Alzheimer's disease, nonsteroidal anti-inflammatory drugs, cognitive decline, disease progression, esomeprazole, gastroprotection, APOE ε4, tertiary prevention, ADAS-Cog
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Cognition Disorders, Female, Humans, Ibuprofen, Male, Severity of Illness Index, Disease Progression, Apolipoprotein E4
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