Three Cardinal Lessons from ADAPT - 10 Years on

The Alzheimer's Disease Anti-inflammatory Prevention Trial was a placebo-controlled three-arm pharmaco-prevention trial of the non-steroidal anti-inflammatory drugs naproxen sodium and celecoxib for prevention of incident Alzheimer's disease (AD) dementia in older (aged 70 and over) adults. Although subjects were at increased risk of symptoms because of a firstdegree family history, they were meant to be cognitively healthy at enrollment. ADAPT encountered several problems that resulted in the termination of its treatments after only two years on average. Interim results were complex but potentially interesting. In the end, however, the results were null. We describe the complications that prevented ADAPT from achieving conclusive results, and suggest that these could have been avoided if the trial design and execution had been better guided by preliminary data. We believe such data should be available before beginning further ambitious phase III trials of this sort, and we suggest a broad method by which such data can be accumulated with reasonable economy.