Project Summary/Abstract Non-Hispanic black (NHB) Americans experience greatly increased risk of Alzheimer’s disease compared to non-Hispanic white (NHW) Americans. Health-related vulnerabilities are linked with biopsychosocial stress, which disproportionately affects NHB populations. Living with chronic pain is stressful. Osteoarthritis (OA) is a highly prevalent and debilitating chronic pain condition that affects NHB adults more severely than NHW adults. Chronic pain is associated with elevated systemic inflammation and increased risk of dementia, both of which disproportionately affect NHB Americans. Additionally, NHB Americans also have elevated genetic and biological markers of dementia but there are weaker relationships between those biomarkers and dementia in NHB than NHW populations. Evidence suggests the amyloid-positive brains of NHB adults appear older than expected. This might be due to ethnic/race groups differences in environmental, sociocultural, and health- related stress exposures. Cumulative exposure across the lifespan might reduce brain reserve and induce vulnerabilities to dementia by taking a toll on the biological system. This suggests life experience factors, including chronic pain, might play a role in neurodegenerative processes. Therefore, ethnicity/race, with consideration for sociodemographic and psychosocial factors, combined with pain severity might serve as a key vulnerability for Alzheimer’s disease. What is not known is whether: 1) NHB and NHW with chronic knee pain differ in biomarkers of inflammation and dementia, and if 2) NHB with high pain severity have relatively greater changes in those biomarkers and global cognition over time compared to their NHW peers. We will use data from an existing R01 to process plasma biomarkers and novel brain MRI biomarkers of inflammation and dementia. We have comprehensive biopsychosocial, MRI, and general cognitive data for 120 adults with evidence of chronic pain (60 NHB, 60 NHW) across a two-year period. Our findings will 1) contribute to an improved understanding of the dynamics between chronic pain, ethnicity/race, and dementia risk; and 2) promote the identification of novel brain MRI biological markers sensitive to stress-related exposure and dementia risk.