PROJECT ABSTRACT: With our aging population and expanding obesity epidemic, the importance of type 2 diabetes (T2D) as a remediable risk factor for cognitive decline has expanded, particularly in underserved communities. T2D is a risk factor for Alzheimer’s disease and related dementias, vascular dementia, mild cognitive impairment and accelerated cognitive decline. Despite abundant evidence linking blood glucose (BG) control to cognitive outcomes, research has failed to show that intensive treatment of diabetes reduces the risk of cognitive decline, perhaps due to increased exposure to hypoglycemia and BG variability. Neither of these important aspects of BG control are captured by standard measures. Similarly, prior research is limited by use of conventional cognitive assessments, which are insensitive to cognitive change. We address these limitations as part of the renewal of the Einstein Aging Study (EAS; NIA P01 AG003949) with a new project that innovatively pairs continuous glucose monitoring (CGM) technology with smartphone-based, ultra-brief, but highly sensitive ambulatory cognitive tests, developed and validated in the previous funding period. Through annual 14-day measurement bursts we will capture the dynamic relationships of BG levels and short-term cognitive variation in real time. We will be better able to examine how BG regulation predicts cognitive decline over 5 years of follow-up. The overarching aim of the proposed project is to examine the short- and long-term effects of various clinically important BG parameters on cognitive performance and decline. The study will enroll 230 racially and ethnically diverse, and predominantly socioeconomically disadvantaged older adults age 60+ with T2D, systematically recruited from our Bronx community. Potential bio-behavioral mediators of short-term effects on cognitive performance include depression symptoms, negative affect, sleep and fatigue; moderators include age, sex, race/ethnicity, amyloid, tau, inflammation, and vascular health. Candidate bio-behavioral mechanisms for effects on long-term cognitive decline associations include depression, negative affect, sleep, inflammation, elevation of AD biomarkers, and markers of vascular disease. Moderators include age, sex, race/ethnicity, amyloid, Tau, inflammation, and vascular health. This research will advance our understanding of the effects of T2D on cognitive performance and decline in a racially and ethnically diverse at-risk population of older adults. Ultimately, this work will facilitate the tailoring of glycemic goals and intervention strategies based on individual patient characteristics.