More recent studies from Masters and colleagues have also demonstrated the time-course over which the Aβ accumulates in the evolution of Alzheimer’s disease, using molecular PET- Aβ imaging, allowing the preclinical and prodromal stages to be identified during life. They have also identified some of the genetic determinants which affect the rates of cognitive decline. These insights into the natural history of Alzheimer’s disease will have a major impact on clinical trial design and provide prognostic information for subjects at risk.