ABSTRACT The aging research community has identified numerous risk factors associated with the full spectrum of cognition including mild cognitive impairment and Alzheimer?s disease (AD), and there is greater understanding of the underlying brain mechanisms. Unfortunately, the vast majority of knowledge comes from studies of primarily non-Hispanic Whites. Although African Americans bear a disproportionate burden of Alzheimer?s disease (AD) and cognitive impairment, the neurobiologic mechanisms underlying these disparities remain elusive. The overall goal of the proposed study is to investigate the underlying neurobiologic mechanisms linking culturally-relevant psychosocial risk factors to cognitive decline and risk of AD in older African Americans. Existing literature with MRI data in older African Americans has focused almost exclusively on cross-sectional associations of cognition or incident AD, and has examined traditional risk factors. Very few studies of African Americans have examined culturally relevant risk factors with repeated measures of cognitive function and brain integrity over time to test the underlying neurobiologic mechanisms linking risk factors to cognitive decline and risk of AD. We propose to interrogate changes in structural and functional integrity on MRI as key neurobiologic substrates linking these socially relevant risk factors to cognitive decline and risk of AD in African Americans. Leveraging the well-established infrastructure of the Minority Aging Research Study (MARS), including available data on risk factors, and repeated measures of cognitive function, we will use a multi-modal neuroimaging approach to acquire antemortem MRI scans on 400 African Americans and quantify change in a number of brain MRI indices to address the Specific Aims. Aim 1 will examine the relation of change in brain MRI indices with rate of cognitive decline and risk of AD among older African Americans; Aim 2 will examine the relation of early and mid-life cultural risk factors with change in structural and functional brain MRI indices among older African Americans; Aim 3 will determine if change in brain MRI indices affects the relation of early- and mid-life risk factors to rate of decline and risk of AD among older African Americans; and taking advantage of neuroimaging and cognitive function data available at no cost from the Rush Memory and Aging Project (MAP), Aim 4 will identify racial differences in the relation of change in MRI structural and functional brain integrity to cognitive decline. Cognitive impairment associated with aging is a large and growing public health problem that disproportionately burdens African Americans. Knowledge of the neurobiologic pathways linking risk factors to cognitive decline will ultimately provide targets for future prevention/intervention studies, and will have a strong and sustained impact on the field.