Non-Steroidal Anti-Inflammatory Drugs as a Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Treatment Effect

Introduction Alzheimer's disease (AD) is the cause of more than two-thirds of all dementia cases. Although there is no effective treatment against this disorder, its association with neuroinflammation suggests that non-steroidal anti-inflammatory drugs (NSAIDs) might represent a potential therapeutic option. Objective The objective of this study was to evaluate the efficacy of NSAIDs in the treatment of AD using a metaanalysis approach. Methods MEDLINE, Web of Science, Science Direct, and the Cochrane Library were used to search all the randomized controlled trials that have evaluated the efficacy of NSAIDs as a treatment for AD (up to 1 October 2014). The overall effect of NSAIDs versus placebo was determined using a random effects model meta-analysis where we compared changes (i.e., mean differences pre-vs. posttreatment) between the two conditions in test scores indicative of cognition, disease severity, and related outcomes. Results Seven studies were finally included in the metaanalysis. Diclofenac/misoprostol, nimesulide, naproxen, rofecoxib, ibuprofen, indomethacin, tarenflurbil, and celecoxib were the NSAIDs used in these reports. The results of the AD Assessment Scale-cognitive subscale (ADAS-cog), the Clinical Dementia Rating Scale sum-of-boxes (CDR-SOB), and the Mini-Mental State Examination (MMSE) showed no statistical or clinical significance of NSAIDs treatment compared with placebo, i. e., mean differences of -0.24 (95 % Confidence Interval (CI) -1.04 to 0.57; P = 0.52), -0.07 (95 % CI -0.7 to 0.56; P = 0.82), and 0.35 (95 % CI -0.34 to 1.04; P = 0.32), respectively. Conclusion Current preliminary evidence suggests no beneficial effect of NSAIDs on cognition or overall AD severity. Thus, although more research is needed in the field, the evidence available does not support the use of NSAIDs for AD treatment.