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.