A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease
| Autor: | Patrizio Pasqualetti, Orazio Zanetti, Cristina Bonomini, Gloria Dal Forno, Elena Sinforiani, Camillo Marra, Luca Paulon, Paolo Maria Rossini |
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| Předmět: |
Male
Aging medicine.medical_specialty APOE e4 Flurbiprofen Apolipoprotein E4 Ibuprofen Disease Severity of Illness Index law.invention Randomized controlled trial law Alzheimer Disease Internal medicine Epidemiology Severity of illness medicine Humans Cognitive decline Aged Aged 80 and over business.industry Anti-Inflammatory Agents Non-Steroidal medicine.disease Alzheimer disease ApoE ε4 carriers Surgery Settore MED/26 - NEUROLOGIA Disease Progression Female Geriatrics and Gerontology Alzheimer's disease business Cognition Disorders medicine.drug |
| Zdroj: | ResearcherID Scopus-Elsevier |
| Popis: | 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.This was a 12-month multicenter, randomized, double-blind, placebo-controlled, parallel group trial. Participants with mild-moderate AD (Mini-Mental State Examination score15,26; 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).Fifty-one patients (77%) in the ibuprofen vs 46 (70%) in the placebo group completed the protocol (p0.20). 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.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. |
| Databáze: | OpenAIRE |
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