PROJECT SUMMARY/ABSTRACT The parent grant leverages the rich, longitudinal data from the Atherosclerosis Risk in Communities (ARIC) Study and Baltimore Longitudinal Study of Aging (BLSA) and uses a data-driven approach to characterize the cognitive heterogeneity of subtle cognitive difficulties in older adults who do not yet show cognitive impairment consistent with mild cognitive impairment (MCI) or dementia. We are then examining the mid- and late-life vascular, physical activity, and Alzheimer’s disease and related dementia (ADRD) biomarker predictors of subtle cognitive decline phenotypes (e.g., low-executive, low-memory) as well as rates of decline on ADRD outcomes. The current proposal for a research supplement to promote diversity in health-related research would provide funding for Fareshte Erani to complete a postdoctoral fellowship in my lab. Through this supplement, she is proposing to extend the parent RF1 to conduct a novel examination of mid- and late-life depressive symptoms on cognitive and biological outcomes in older adults. Her long-term career goal is to be an ADRD researcher with an independent research program focused on the intersection of neuropsychiatric factors, neural networks, and cognitive decline in order to guide individualized intervention efforts. Support from the diversity supplement will leverage her existing expertise while also providing Ms. Erani with advanced training and mentorship in ADRD research, depression and relevant cognitive outcomes and mechanisms, skills to conduct longitudinal statistical analyses, and tools to submit an NIA K-award application. Depression has been associated with lower cognitive performance in older adults and increased risk for dementia; however, there is likely considerable heterogeneity in causal mechanisms since longstanding, chronic depression could be a causal link to subsequent cognitive impairment and/or late-life depression could be co- occurring with an ADRD process. The proposed study will use ARIC and BLSA data to investigate the role of depression onset and cognitive decline by examining associations of mid- and late-life onset depressive symptoms with cognitive and biological outcomes. Specifically, we will 1) examine the extent to which mid- and late-life depressive symptoms among cognitively unimpaired older adults predict late-life subtle cognitive decline phenotypes and progression to MCI/dementia and 2) examine the associations of mid- and late-life depressive symptoms with fronto-cingulate regions on neuroimaging, markers of inflammation, and ADRD plasma markers. We will also explore neuroimaging, inflammatory, and ADRD biomarker variables that mediate the associations of mid- and late-life depressive symptoms and subtle cognitive decline. Examining the associations between depressive symptom onset, profiles of subtle cognitive difficulties, and the neural mechanisms that link depressive symptoms and cognitive decline will enhance our understanding of the d...