Anti-inflammatory therapy for Alzheimer's disease: implications of the prednisone trial.
The inflammatory hypothesis of Alzheimer's disease (AD), which is supported both by basic laboratory evidence and epidemiological studies, suggests that treatment with anti-inflammatory drugs may reduce the risk or slow the progression of AD. In the first large-scale test of this hypothesis, the Alzheimer's Disease Cooperative Study (ADCS) conducted a randomized placebo-controlled trial of low-dose prednisone treatment in subjects with probable AD. There was no difference in cognitive decline between the prednisone and placebo treatment groups; subjects treated with prednisone showed behavioral decline compared to those in the placebo group. While this study indicates that a low-dose regimen of prednisone is not useful in the treatment of AD, it does not refute the inflammatory hypothesis; recent evidence supports testing of a number of alternative anti-inflammatory regimens, for prevention and/or treatment of AD. The ADCS has initiated a trial to determine whether treatment with a non-selective non-steroidal anti-inflammatory drug or a selective cyclooxygenase-2 inhibitor is effective in slowing the rate of cognitive decline in AD.
Department of Neurology, Georgetown University Medical Center, Washington, DC 20007, USA. psa@gunet.georgetown.edu
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D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D051546:Cyclooxygenase 2; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D010919:Placebos; D011241:Prednisone / Q000494:pharmacology* / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D010919:Placebos; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D011241:Prednisone