Project 1 Project Summary Almost all studies of Alzheimer disease (AD) investigating “molecular biomarkers” that reflect the brain lesions of the disorder are conducted in research volunteers who overwhelmingly are of the non-Hispanic white race. Project 1 of the Healthy Aging and Senile Dementia (HASD) Program Project Grant will use the molecular biomarkers of AD to predict which cognitively normal older adults will develop its symptoms (i.e., dementia). However, Project 1 also will examine potential racial differences in these molecular biomarkers between African Americans and non-Hispanic whites. To accomplish its Aims, Project 1 will interact closely with other components of HASD to innovatively increase the number of African American research volunteers who participate in molecular biomarker procedures, including positron emission tomography (PET) imaging studies and lumbar puncture to obtain cerebrospinal fluid (CSF) for analysis. The Specific Aims of Project 1 are to: 1. Compare molecular biomarkers of AD (i.e., amyloid PET, tau PET, and CSF measures of amyloid- beta42 and tau) at baseline and longitudinally in African Americans and non-Hispanic whites. 2. Compare in African Americans and non-Hispanic whites the rates of conversion from cognitively normal to symptomatic AD. 3. Correlate the results from Specific Aims 1 and 2 with other variables obtained in HASD: clinical information (including the presence of comorbid disorders, such as cerebrovascular disease, and socioeconomic status), cognitive measures, indicators of sleep disruption, genetic variants for risk and protection, imaging measures (including magnetic resonance imaging and PET studies of the brain), and CSF analytes. 4. Increase the number of brain autopsies in African Americans to compare the neuropathological features of AD, including the presence of comorbid diseases, with non-Hispanic whites.