$66,521,567

ALZHEIMER'S DISEASE AND ALZHEIMER'S DISEASE RELATED DEMENTIAS IN PREDIABETES AND TYPE 2 DIABETES: THE DIABETES PREVENTION PROGRAM OUTCOMES STUDY AD/ADRD PROJECT - THIS U19 PROPOSAL FOCUSES ON ONE OF THE MOST IMPORTANT, COMPLEX QUESTIONS IN ALZHEIMER’S DISEASE (AD) AND ALZHEIMER’S DISEASE-RELATED DEMENTIAS (ADRD) RESEARCH: WHAT ARE THE DETERMINANTS AND THE NATURE OF COGNITIVE IMPAIRMENT AMONG PERSONS WITH PRE-DIABETES (PRED) AND TYPE 2 DIABETES (T2D), WHO ARE A HIGH-RISK GROUP FOR COGNITIVE IMPAIRMENT AND REPRESENT A LARGE FRACTION OF THE UNITED STATES (US) POPULATION? DESPITE KNOWLEDGE THAT PERSONS WITH PRED AND T2D ARE A HIGH-RISK GROUP FOR COGNITIVE DECLINE, MILD COGNITIVE IMPAIRMENT (MCI), AND DEMENTIA, THE RISK FACTORS, MECHANISMS, AND NEUROPATHOLOGY OF COGNITIVE IMPAIRMENT IN PERSONS WITH PRED AND T2D REMAIN UNCLEAR. GAPS IN KNOWLEDGE ON COGNITIVE IMPAIRMENT IN PRED AND T2D INCLUDE: (A) THE ROLE OF AD AND/OR NON-AD NEUROPATHOLOGY BEYOND VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA (VCID); (B) THE ROLE OF GLYCEMIA, RELATED METABOLIC FACTORS SUCH AS HYPERINSULINEMIA, AND TRADITIONAL MICRO AND MACROVASCULAR COMPLICATIONS OF PRED/T2D; (C) THE ROLE OF GLUCOSE-LOWERING MEDICATIONS, PRIMARILY METFORMIN; AND (D) THE ROLE OF PHYSICAL ACTIVITY, PHYSICAL FUNCTION, AND FRAILTY, KEY IN PRED AND T2D. WE PROPOSE 4 INTERRELATED PROJECTS THAT WILL ADDRESS THESE GAPS, LEVERAGING THE DIABETES PREVENTION PROGRAM (DPP) OUTCOMES STUDY (DPPOS) COHORT AND ITS DETAILED PRED/T2D PHENOTYPING, ADDING STATE OF THE ART AD/ADRD PHENOTYPING. THE DPPOS COHORT CURRENTLY HAS A MEAN AGE OF 72 YEARS, WITH 76% OVER THE AGE OF 65. THUS, THE COHORT IS IN A PERIOD OF THE LIFESPAN WHEN THE DEVELOPMENT OF COGNITIVE DECLINE, MCI, AND DEMENTIA ACCELERATES. THIS EXTENSIVELY PHENOTYPED COHORT REPRESENTS AN ESTIMATED 50 MILLION AMERICANS. TO ADDRESS THIS PROPOSAL’S COMPLEX INTERRELATED QUESTIONS, WE WILL PERFORM TWO WAVES OF STATE-OF-THE-ART AD/ADRD PHENOTYPING DURING THE PROPOSED 5-YEAR FUNDING PERIOD, INCLUDING COMPREHENSIVE COGNITIVE ASSESSMENTS AND SYNDROME ADJUDICATION AND PLASMA AND BRAIN IMAGING BIOMARKERS OF AD/ADRD. WE WILL ADDRESS THE COMPLEX OVERARCHING QUESTION OF OUR PROJECT THROUGH THE FOLLOWING AIMS: (1) TO ESTABLISH 5 CORES TO SUPPORT THE 4 INTEGRATED SCIENTIFIC PROJECTS: AN ADMINISTRATIVE CORE, A CLINICAL OPERATIONS AND PROCEDURES CORE, A COGNITIVE ASSESSMENT AND ADJUDICATION CORE, A NEUROIMAGING AND PLASMA BIOMARKERS CORE, AND A BIOSTATISTICS AND DATA INFRASTRUCTURE CORE: (2) TO CONDUCT 4 INTEGRATED PROJECTS FOCUSED ON KEY ASPECTS OF THE CENTRAL QUESTION OF THIS PROPOSAL: PROJECT 1 WILL EXAMINE THE ASSOCIATION OF COGNITIVE DECLINE, MCI, AND DEMENTIA IN THE DPPOS COHORT WITH BIOMARKERS OF NEUROPATHOLOGY AND BRAIN INSULIN SIGNALING, AND WITH SOCIODEMOGRAPHIC AND BEHAVIORAL FACTORS; PROJECT 2 WILL EXAMINE THE ASSOCIATIONS OF CUMULATIVE GLYCEMIA, RELATED METABOLIC FACTORS, AND MICROVASCULAR AND MACROVASCULAR COMPLICATIONS, WITH COGNITIVE SYNDROMES AND BIOMARKERS OF NEUROPATHOLOGY; PROJECT 3 WILL EXAMINE THE ASSOCIATION OF CUMULATIVE EXPOSURE TO METFORMIN AND OTHER T2D MEDICATIONS WITH COGNITIVE SYNDROMES AND BIOMARKERS OF NEUROPATHOLOGY; PROJECT 4 WILL EVALUATE THE ASSOCIATION OF TRAJECTORIES OF PHYSICAL ACTIVITY, PHYSICAL FUNCTION AND FRAILTY WITH COGNITIVE SYNDROMES AND BIOMARKERS OF NEUROPATHOLOGY.

Verbatim from USAspending.gov. Capitalization, abbreviations, and codes are unchanged.

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• 2026-04-20SUSTAIN AND ACCELERATE A COMPREHENSIVE HIV RESPONSE IN THE UNITED REPUBLIC OF TANZANIA UNDER PEPFAR - ICAP IS UNIQUELY POSITIONED TO LEAD THE MULTI-YEAR SUSTAIN AND ACCELERATE A COMPREHENSIVE HIV RESPONSE IN THE UNITED REPUBLIC OF TANZANIA (TZ) UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR) ON BEHALF OF CDC IN TZ. ICAP HAS BEEN A PREMIER U.S. GOVERNMENT IMPLEMENTING PARTNER (IP) IN TZ SINCE 2005, FIRST AS A PEPFAR-FUNDED HEALTH FACILITY (HF) IP THAT TRANSITIONED ACTIVITIES TO THE MINISTRY OF HEALTH (MOH) AND LOCAL NON-GOVERNMENTAL ORGANIZATIONS (NGO) (2005?2014); NEXT CONDUCTING KEY STUDIES TO INFORM THE HIV LANDSCAPE AND BUILDING HEALTHCARE WORKER CAPACITY THROUGH INNOVATIVE LEARNING PLATFORMS; AND FOR THE LAST FIVE YEARS AS A COMMUNITY IP WITH ITS PEPFAR-FUNDED FIKIA (?TO REACH? IN KISWAHILI) PROJECT. AS A DRIVING FORCE BEHIND MANY OF TZ?S STRIDES IN PREVENTION, TESTING, TREATMENT INITIATION, AND VIRAL LOAD (VL) SUPPRESSION, ICAP NOW PROPOSES TO TRANSFORM CLIENT-CENTERED HIV TESTING, PREVENTION, AND TREATMENT SERVICES OVER THE NEXT FIVE YEARS. THIS PROJECT RESPONDS TO TZ?S GENERALIZED HIV EPIDEMIC WITH 4.8% ADULT PREVALENCE AND APPROXIMATELY 1.7 MILLION PEOPLE LIVING WITH HIV (PLHIV). AS OF 2019, 83% OF PLHIV IN TZ KNOW THEIR STATUS, 75% OF ALL PLHIV ARE ON ANTIRETROVIRAL THERAPY (ART), AND 69% ARE VIRALLY SUPPRESSED, WITH SIGNIFICANT VARIATIONS IN GEOGRAPHY AND POPULATIONS ACROSS THESE GLOBAL TARGETS. TO ACHIEVE THE 95-95-95 GOALS, TZ MUST IMPROVE SERVICE COVERAGE AND QUALITY FOR MEN, ESPECIALLY THOSE IN MIGRATORY OCCUPATIONS, AND CHILDREN, WHO FALL BEHIND ACROSS THE CASCADE; ONLY 81% AND 66%, RESPECTIVELY, OF PLHIV IN THESE GROUPS KNOW THEIR STATUS. THE RESPONSE WILL ALSO TAILOR INTERVENTIONS TO MEET THE NEEDS OF ADOLESCENT GIRLS AND YOUNG WOMEN AT HIGH RISK OF ACQUIRING HIV, AND KEY POPULATIONS FACING STIGMA, DISCRIMINATION, AND HIGH HIV PREVALENCE, INCLUDING PEOPLE WHO INJECT DRUGS (36%), FEMALE SEX WORKERS (26%), AND MEN WHO HAVE SEX WITH MEN (25%).THE PURPOSE OF THIS PROJECT IS TO PROVIDE RAPID, FLEXIBLE SUPPORT TO AC CELERATE EVIDENCE-BASED HIV PREVENTION AND TREATMENT PROGRAM IMPLEMENTATION IN HF AND COMMUNITIES AND ALIGNED HEALTH SYSTEMS STRENGTHENING ACTIVITIES TOWARD EPIDEMIC CONTROL IN TZ. WORKING DIRECTLY ALONGSIDE REGIONAL AND COUNCIL HEALTH MANAGEMENT TEAMS (R/CHMT), ICAP WILL PROVIDE A TAILORED PACKAGE OF TECHNICAL SUPPORT FEATURING: 1) MULTI-MODAL TRAINING AND HUMAN RESOURCES FOR HEALTH CAPACITY BUILDING; 2) STRENGTHENED SERVICE CONTINUITY ACROSS HEALTH FACILITY (HF) AND COMMUNITY SETTINGS USING DIFFERENTIATED SERVICE DELIVERY MODELS; 3) AND COLLABORATIVE CONTINUOUS QUALITY IMPROVEMENT (CQI) AT HF, REGIONAL, AND NATIONAL LEVELS. ANTICIPATED SHORT TERM OUTCOMES INCLUDE: IMPROVED IDENTIFICATION AND TIMELY INITIATION ON ART OF ALL NEWLY IDENTIFIED HIV+ CLIENTS, INCLUDING HARD-TO-REACH SUB-GROUPS IN SUPPORTED LOCATIONS; INCREASED ART COVERAGE, ADHERENCE, RETENTION, AND VL TESTING OF PLHIV, AMONG ALL SUB-GROUPS; INCREASED COVERAGE OF OPTIMAL ART REGIMENS AMONG ALL SUB-GROUPS; IMPROVED COVERAGE OF COMPREHENSIVE CARE SERVICES, SUCH AS DETECTION AND TREATMENT OF OPPORTUNISTIC INFECTIONS AND PROVISION OF TUBERCULOSIS PREVENTIVE THERAPY; INCREASED COVERAGE OF HIV PREVENTION SERVICES INCLUDING VOLUNTARY MEDICAL MALE CIRCUMCISION, PRE-EXPOSURE PROPHYLAXIS AND MEDICATION ASSISTED TREATMENT, AMONG TARGETED GROUPS; INCREASED HIV-EXPOSED INFANTS RECEIVING EARLY DIAGNOSIS AT SUPPORTED HF IN LINE WITH NORMATIVE GUIDANCE; AND ENHANCED MONITORING AND EVALUATION SYSTEMS IN PLACE FOR IMPROVED DATA COLLECTION, DATA QUALITY, AND OVERSIGHT OF PROGRAM PERFORMANCE.THIS PROJECT WILL OPTIMIZE ICAP?S EXTENSIVE PARTNER NETWORK BUILT OVER 17 YEARS IN TZ COLLABORATING WITH GOVERNMENT OF TZ PARTNERS, LOCAL INSTITUTIONS THAT OVERSEE THE HEALTH SYSTEM (E.G., RHMT IN THE FOUR TARGET REGIONS, ALL 32 RELATED CHMT); A ROBUST NGO NETWORK, AND OTHER STRATEGIC COLLABORATORS. ICAP BUILDS LONG-TERM, HIGH-IMPACT RELATIONSHIPS THAT HELP AD$117.5M
• 2026-04-20ADVANCING SUSTAINABLE IMPLEMENTATION OF COMPREHENSIVE HIV/TB SERVICES FOR EPIDEMIC CONTROL IN THE REPUBLIC OF MOZAMBIQUE UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR)$105.5M
• 2026-05-05CENTER FOR HIGH-THROUGHPUT MINIMALLY-INVASIVE DOSIMETRY$90.8M
• 2026-02-20CANCER CENTER SUPPORT GRANT$85.5M
• —STRENGTHENING REGIONAL, NATIONAL, AND SUBNATIONAL INSTITUTIONAL CAPACITIES TO SUSTAINABLY COMBAT HIV/AIDS AND TUBERCULOSIS UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR)$39.9M