A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease

Patrizio Pasqualetti, Cristina Bonomini, Gloria Dal Forno, Luca Paulon, Elena Sinforiani, Camillo Marra, Orazio Zanetti, Paolo Maria Rossini

Research output: Contribution to journalArticlepeer-review


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 Aβ-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, 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 ε4 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 ε4 carrier status.

Original languageEnglish
Pages (from-to)102-110
Number of pages9
JournalAging clinical and experimental research
Issue number2
Publication statusPublished - Apr 2009


  • Alzheimer disease
  • ApoE ε4 carriers
  • Cognitive decline
  • Ibuprofen

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

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