Alzheimer's disease (AD) affects one in ten people over 65 years of age and about half of people over 85. With people living longer than ever, the number of patients with AD could double every 20 years, potentially leading to a financially overwhelming epidemic. Against this backdrop, some researchers are calling for a fundamental change in the way AD preventive treatment trials are done and in the evidence that bodies such as the US Food and Drug Administration should accept before licensing treatments. But who would have thought that much of this change would depend on a few people living in a remote part of South America?

 

“Now is the time to launch the era of Alzheimer's prevention research”, says Eric Reiman (Banner Alzheimer's Institute [BAI], Phoenix, AZ, USA), a leading voice in the call for change under the flag of the Alzheimer's Prevention Initiative. “Currently, it takes too many cognitively normal people, too much money, and too much time—longer than the life of a drug product's patent—to evaluate presymptomatic AD treatments in a randomised trial using clinical endpoints. We need to establish the means to evaluate a range of promising presymptomatic treatments using AD biomarkers that are reasonably likely to predict a clinical benefit [if we are to] find a treatment that works as quickly as possible, [and create] an accelerated regulatory approval pathway.”

AD trials have suffered from serious problems. Most have involved people who are close to developing or already showing the first signs of the disease—when it might be too late for a treatment to have much effect—and those involving clearly presymptomatic people have been encumbered by the numbers of participants required (only one in ten people might naturally develop AD by 65 years of age). Furthermore, regulatory bodies require that clinical benefit be shown before a treatment is approved, meaning that preventive trials in presymptomatic people would need to run for years, incurring huge financial burdens.

 

Reiman and his colleagues at the BAI suggest something quite different should be done: that promising treatments should be tested in presymptomatic trials lasting just 2 years in groups of people who are very likely to develop AD, that a range of AD biomarkers be simultaneously followed over this period, and that the extent to which their movement predicts the clinical benefit a treatment might have be recorded.