INVESTIGATING APOE-TOMM40 HAPLOTYPES, SOCIAL FACTORS, AND VASCULAR RISK FACTORS ON COGNITIVE DECLINE - PROJECT SUMMARY THE APPLICANT SEEKS THIS NRSA F31 AWARD TO GAIN A DEEPER UNDERSTANDING OF THE GENETIC, SOCIAL, AND VASCULAR FACTORS THAT CONTRIBUTE TO COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD) IN BLACK COMMUNITIES. TO ACHIEVE THESE GOALS, THE APPLICANT PLANS TO (1) DEVELOP EXPERTISE IN THE ANALYSIS AND INTERPRETATION OF T2 (FLAIR) AND T1 (STRUCTURAL) NEUROIMAGING METHODS AS THEY RELATE TO AD AND COGNITIVE DECLINE; (2) DEVELOP AN EXPERTISE IN THE IMPLEMENTATION OF ADVANCED STATISTICAL METHODS WHICH INCORPORATE RISK FACTORS FOR AD PHENOTYPES; AND (3) PROFESSIONAL DEVELOPMENT. WITH GUIDANCE FROM HER EXPERT MENTORSHIP TEAM, INCLUDING DR. KACIE DETERS (SPONSOR), DR. KEITH VOSSEL (CO-SPONSOR), DR. DANIEL SILVERMAN (MENTOR), AND DR. ELIZABETH ROSE MAYEDA (MENTOR), AND THROUGH A TAILORED TRAINING PLAN, THE APPLICANT WILL DEVELOP THE SKILLS NECESSARY TO COMPLETE THE PROPOSED RESEARCH GOALS WHILE POSITIONING HERSELF TO SUCCESSFULLY TRANSITION TO A POSTDOCTORAL POSITION. THE OVERALL RESEARCH GOAL OF THIS F31 APPLICATION IS TO INVESTIGATE THE INTERSECTION OF APOE-TOMM40 '523 HAPLOTYPE VARIANTS, SOCIAL, AND VASCULAR RISK FACTORS (LIFESTYLE VASCULAR RISK COMPOSITE SCORE; VASCULAR BURDEN MEASURED AS WHITE MATTER HYPERINTENSITIES) ON COGNITIVE DECLINE TRAJECTORIES. EVIDENCE SUGGESTS THAT SOME POPULATIONS ARE AT GREATER RISK OF COGNITIVE IMPAIRMENT AND ADRDS. ALTHOUGH PREDICTORS OF ADRDS MAY HAVE DIFFERENT EFFECTS IN ACROSS POPULATIONS, MOST RESEARCH TO DATE DOES NOT FULLY REFLECT THE DEMOGRAPHICS OF THE POPULATIONS MOST AFFECTED, LEAVING A GAP IN OUR UNDERSTANDING OF THE FACTORS CONTRIBUTING TO THE ELEVATED RISK OF COGNITIVE DECLINE IN THESE UNDERSTUDIED COMMUNITIES. AIM 1 WILL INVESTIGATE HOW APOE- TOMM40 '523 HAPLOTYPES ARE ASSOCIATED WITH BASELINE VASCULAR HEALTH AND WILL INVESTIGATE HOW ADVERSE SOCIAL FACTORS INFLUENCE THESE ASSOCIATIONS. IN AIM 2, THE APPLICANT WILL CONDUCT A MEDIATION ANALYSIS TO ASSESS IF VASCULAR RISK FACTORS MEDIATE THE ASSOCIATION OF APOE-TOMM40 '523 AND COGNITIVE DECLINE. UNDERSTANDING HOW GENETIC FACTORS INFLUENCE VASCULAR HEALTH BEFORE THE ONSET OF COGNITIVE IMPAIRMENT IS CLINICALLY IMPORTANT, AS IT COULD IDENTIFY MODIFIABLE VASCULAR FACTORS WHICH OFFERS A CRUCIAL WINDOW FOR EARLY INTERVENTION, POTENTIALLY SLOWING OR PREVENTING THE PROGRESSION TO ADRD IN PARTICULARLY SUSCEPTIBLE GROUPS. THIS WORK UNDERSCORES THE NEED TO STUDY BOTH BIOLOGICAL AND SOCIAL FACTORS IN COGNITIVE HEALTH TO INFORM EARLY INTERVENTIONS AND SUPPORT THE DEVELOPMENT OF PRECISION MEDICINE. THE TRAINING PROVIDED BY THE MENTORSHIP TEAM WILL PREPARE THE APPLICANT FOR FUTURE FUNDING OPPORTUNITIES AND A SUCCESSFUL ACADEMIC CAREER, INCLUDING POSTDOCTORAL TRANSITION AWARDS AND ULTIMATELY K99-R00 SUPPORT.