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.