Project Summary/Abstract Underrepresented ethnic/race groups have a disproportionately higher incidence of Alzheimer’s disease and related dementias (ADRD) with numbers expected to double by 2060. Numerous health conditions increase risk of ADRD including chronic pain. Although an extensive body of research indicates underrepresented ethnic/race groups are at greater risk for these health conditions than non-Hispanic white (NHW) adults, a growing body of evidence indicates socioenvironmental factors contribute to these disparities. Socioenvironmental factors influence functioning in both the body and the brain and are linked with cognitive decline and ADRD. We have findings indicating that in individuals with high chronic pain severity, non-Hispanic black (NHB) adults with fewer socioenvironmental resources had significantly thinner temporal cortical gray matter than non-Hispanic white (NHW) adults with greater socioenvironmental resources. Additionally, dispositional traits are neurobiologically- based and a strong body of evidence has linked certain traits with risk of ADRD onset. We have shown dispositional traits are not only associated with pain and psychosocial stress but also related to a measure of brain age and influenced by socioenvironmental factors. The proposed project will extend the scientific merit of the Pain Relief for OsteoArthritis through Combined Treatment (PROACT) study by leveraging available data and broadening the scope of research to elucidate previously uninvestigated relationships between chronic pain, socioenvironmental factors, dispositional traits, and brain structural and functional measures contributing to disparities in neurobiological vulnerabilities and increased ADRD risk. The PROACT study (ClinicalTrials.gov Identifier: NCT03884374) is a clinical trial in the fourth year of data collection (R37, PI: R. Fillingim) conducted at the University of Florida (UF) and the University of Alabama at Birmingham (UAB). PROACT will recruit 360 study participants with equal representation of NHB and NHW adults with knee pain associated with osteoarthritis. Participants are randomized to one of four groups: transcranial direct current stimulation (tDCS), or Sham tDCS with breathing and attention training (BAT) or Sham BAT. Participants are seen for five sessions over a period of a week and will complete baseline and post-intervention brain MRIs. In addition to investigating brain structure and brain age, the pre/post functional imaging data will provide the unique opportunity to determine if chronic pain severity, socioenvironmental status, and dispositional traits predict individual differences in treatment response. The long-term goals of this line of investigation are to improve clinical care by identifying factors to assist in determining which individuals are at greatest risk for ADRD and other health conditions and to enhance individualized treatment interventions to improve health for all.