An important element of the design of the ROS and MAP studies is that all individuals are without known dementia at the time of entry into the study. Their cognitive trajectory is captured using a detailed battery of neuropsychological tests that is deployed annually to all living subjects. Subjects are also evaluated neurologically every year, and, at the time of death, a review of all ante-mortem data leads to a final clinical diagnosis for each participant: each individual receives a diagnosis of syndromic Alzheimer’s disease (AD), of mild cognitive impairment (MCI), or of no cognitive impairment (NCI). After the autopsy is concluded, a spectrum of neuropathologic diagnoses are obtained, such as a pathologic diagnosis of AD as defined using the modified NIA Reagan criteria based13 on a modified Bielschowsky silver stain to visualize amyloid plaques and neurofibrillary tangles. Brain sections are stained with hematoxylin and eosin to measure cerebral infarcts, and immunochemistry is used to measure Lewy bodies. Details of each pathologic diagnosis captured in these cohorts were described previously14. However, many other pathologies are present in the brains of
