Commentary on “A roadmap for the prevention of dementia: The inaugural Leon Thal Symposium”

Although therapies for clinically manifest Alzheimer’s disease (AD) that slow the underlying pathologic process and rate of progression are not yet available, the work of Leon Thal and others has led to an increasing number of such potential disease-modifying investigational agents that are now in or nearing the middle and later stages of clinical testing. Although there is great optimism that one or more of these investigational agents might prove effective and safe for treating patients with mild to moderate AD, it is also clear that such disease-modifying treatments might have their greatest potential when used early, preferably even before onset of the pathologic process. It seems intuitively obvious to us that treatments that actually prevent ADrelated neurodegeneration are more likely to be effective AD “therapies” than those that simply slow its progression or stop it altogether. In considering the challenges of discovering and developing drug therapies to prevent dementia, we would like to extend discussion of the “roadmap” Leon Thal Symposium Report on several fundamental questions. First and foremost, what exactly are we trying to prevent? Second, what and when to treat? We will also address several critical logistical challenges to developing drugs that effectively treat and prevent dementia, ie, from the perspective of current pharmaceutical research and development.