Commentary on “Developing a national strategy to prevent dementia: Leon Thal Symposium 2009.” Methodologic considerations for preventing Alzheimer's disease by 2020

The following position paper focuses on some methodologic considerations that will affect progress toward the goal of the Campaign to Prevent Alzheimer’s Disease by 2020 (PAD2020) initiative. In this sense, they are domain-independent, irrespective of the specific scientific knowledge that will be discovered during the course of the PAD2020 initiative. The methodologic considerations discussed here have the potential to affect the way decisions are made, the breadth of participation across eligible centers, and the way data are analyzed and interpreted. At the Thal Symposium in November 2009, there was a consensus of opinion that a national, and possibly international, multicenter registry of subjects was needed to (1) better identify Alzheimer’s disease (AD) genetic and environmental risk factors; (2) study candidate biomarkers; (3) better characterize cognitive, functional, and behavioral change in normal aging and AD; (4) detect cohorts of asymptomatic and very mildly affected AD subjects; (5) improve sample selection for research and clinical trials of asymptomatic and very mild AD; and (6) improve the methods of measuring change due to aging, disease, and treatment. In the past, selection of a common test battery for a collaborative effort such as the PAD2020 initiative has been driven by consensus opinion. However, a consensus approach can result in suboptimal test selection as well as produce three types of bias: (1) bias due to the selected tests themselves; (2) bias due to nonparticipation by centers that prefer other tests; and (3) bias due to the loss of information or strengths contained among tests not selected for inclusion. It would be more optimal if a variety of tests of a given abilitydcognitive, functional, or behavioraldwere