ADNI3 builds on the efforts of first and second phases of ADNI and seeks to identify the earliest changes in brain structure and function as people transition from normal cognitive aging to mild cognitive aging (MCI) and early AD. In addition to continuing to follow approximately 697 subjects from the first and second phase annually (approximately 295 cognitively normal controls, 274 subjects with MCI, and 128 subjects with dementia diagnosed as AD), ADNI3 proposes to enroll approximately 371 new subjects (approximately 133 cognitively normal controls, 151 subjects with MCI, and 87 subjects with dementia diagnosed as AD), while collecting clinical, cognitive, MRI (structural, diffusion, perfusion, resting state), amyloid PET, FDG PET, cerebrospinal fluid (for Aβ, tau, phosphotau, and other proteins), and genetic and autopsy data. In addition, the grant proposes to perform longitudinal measurements of brain tau PET on all subjects. Furthermore, the Project will also enhance its current clinical batteries by adding computerized cognitive testing, and a performance-based functional assessment, and its genetics methodology by including a novel systems biology/modeling analysis approach.