The number of persons with AD is expected to increase markedly in the coming decades [1,2]. With a public health problem of this magnitude, disease prevention provides the best long-term strategy for reducing the burden of cognitive impairment in the U.S. [3,4]. Disease prevention requires the identification of risk factors for cognitive decline and the development of strategies to delay the onset of cognitive impairment through behavior modification or pharmacologic interventions. However, this goal has proved elusive [5,6] due to the complexity of the disease. Although a general consensus regarding the clinical and pathologic diagnoses of AD had emerged by the mid 1980's [7,8], it was subsequently found that AD pathology can be widespread in persons without dementia [9–13]. Some investigators suggested that these persons had greater brain reserve [9].
