title: A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Medical Statistics & Information Technology, Fatebenefratelli Association for Research, Isola Tiberina, Rome, Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pasqualetti
authors.forename: Cristina
authors.initials: C
authors.lastname: Bonomini
authors.forename: Gloria
authors.initials: G
authors.lastname: Dal Forno
authors.forename: Luca
authors.initials: L
authors.lastname: Paulon
authors.forename: Elena
authors.initials: E
authors.lastname: Sinforiani
authors.forename: Camillo
authors.initials: C
authors.lastname: Marra
authors.forename: Orazio
authors.initials: O
authors.lastname: Zanetti
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D053327:Apolipoprotein E4 / Q000235:genetics; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D008297:Male; D012720:Severity of Illness Index
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053327:Apolipoprotein E4; D007052:Ibuprofen