Core Leaders: Jaideep Kapur, MBBS, PhD, & Carol Manning, PhD, ABPP-CN

The overall mission of the Administrative Core is to provide the coordinating infrastructure to integrate the Virginia Alzheimer’s Disease Center (VADC) cores, actively promoting Team Science approaches, and to foster collaborative research on aging and dementia. The VADC’s focused research will contribute basic knowledge about AD, as well as evidence for improved prevention, diagnosis, and intervention strategies. The Administrative Core provides foundational infrastructure to enable all cores to meet their goals and function synergistically.

Core Leaders: George Bloom, PhD, & Harry Sontheimer, PhD

One of the most daunting obstacles to developing effective methods for preventing and managing ADRD has been a poor understanding of fundamental disease mechanisms at the cellular and molecular levels. Multiple complex factors contribute to dementias, starting with classical AD pathology of amyloid-β (Aβ) plaques and tau tangles, compounded by metabolic contributions, neurovascular dysfunction that provokes vascular dementia, and central and peripheral neuro-immune responses. Modifiable factors in ADRD include hypertension, metabolic parameters such as high BMI, exercise, diet, and cerebral Aβ load, which can be reduced by passive immunization. The primary focus of VADC is on vulnerable rural populations, care partners, and Black Americans, all of whom face chronic socioeconomic stress, which manifests biologically and clinically as an allostatic load: high BMI, metabolic syndrome, hypertension, and disrupted sleep patterns. The BSC connects resources with researchers and serves as a formal consortium to foster the exchange of ideas and collaborations between basic scientists and clinicians.

Core Leader: Stuart Berr, PhD

The Biomarker Core (BC) focuses on collecting and storing biomarkers to monitor Alzheimer's disease severity, progression, and treatment effects. Biomarkers obtained from blood, cerebral spinal fluid, and neuroimaging will be analyzed for individuals with dementia, their care partners, and healthy controls. The BC aims to explore relationships between genetic and relational aspects of dementia, stress biomarkers, and increased dementia risk for care partners. Imaging data will provide additional biomarkers to understand the disease and monitor its severity and progression. The BC collaborates with other cores to integrate amyloid and tau burden measurements, structural MRI, histological information, clinical assessment, and genetic data analysis. The BC also supports investigators with project planning, data analysis, interpretation, and educational opportunities related to imaging. Its mission is to facilitate research on biomarkers for Alzheimer's disease and related dementias, deepen understanding of their interactions, and develop new techniques for detection and progression monitoring. The BC aims to provide state-of-the-art resources, tools for early AD detection, and novel image acquisition and analysis techniques.

Core Leaders: Anelyssa D'Abreu, MD, MPH, & Carol Manning, PhD, ABPP-CN

The mission of the Virginia Alzheimer’s Disease Center (VADC) CC is to facilitate cross-sectional and longitudinal studies in persons with dementia (PWDs), care partners (CP), with an emphasis on Black and rural participants examining the influence of health disparities on cognitive decline, psychological health, and sleep. The CC will accomplish this by working with the Outreach, Recruitment and Engagement Core to maintain a trial-ready cohort of diverse research participants in the VADC Registry to support research on Alzheimer’s disease and related dementias (ADRD) and caregiving,. Due to the University of Virginia’s location in central Virginia and our catchment area, we are positioned to recruit a large number of rural and Black individuals from lower socioeconomic levels who are often underrepresented in national registries and ADRD research. The CC will also enroll dyads of PWDs and their CPs (minimum = 150 dyads) from the VADC Registry and other community recruiting mechanisms into the VADC Clinical Cohort. Biopsychosocial data will be collected annually from PWDs, CPs, and healthy controls (50% matched to PWDs and 50% matched to CP groups). The CC has the following primary aims: 1) Support rigorous, novel ADRD research investigating the impacts of behavioral, biological, and socioenvironmental determinants of health on aging, cognitive decline, and caregiving using biomarkers and assessments reflecting health disparities; 2) support systematic research on biopsychosocial and environmental impacts of ADRD within and between dyads of PWDs and CPs; and  3) characterize environmental, subjective, and physiological outcomes of CPs’ stress using validated psychological and physiological measures of allostatic load,  the cumulative burden of chronic stress, sleep disturbances, and negative life experiences. We will accomplish these aims by collecting Uniform Data Set measures and health disparities biomarkers (i.e., biomarkers associated with differential health outcomes in populations with historically relatively low access to resources and high psychological stress/allostatic load – including heart rate, body mass index, complete serum metabolic panel, serum cholesterol, c-reaction protein, A1C), health disparities questionnaires (i.e., measures of social determinants of health, daily experienced discrimination, time scarcity, rurality, neighborhood advantage, physical activity, overall well-being), caregiving questionnaires (i.e., measures of caregiving intensity, duration, readiness, cultural justification, preparedness, knowledge), sleep measures (self-report and objective markers), and ATN biomarkers (e.g., brain MRI, amyloid and tau PET, amyloid and tau serum, and CSF). The Clinical Core collaborates with the other Cores to collect, store, analyze, and share novel, comprehensive longitudinal data to support NAPA goals of inclusive research focused on the wide-ranging impacts of dementia on families and diverse populations. We will contribute a unique dataset to national registries regarding social determinants of health, stress, and sleep among rural and underrepresented PWDs and CPs. 

Core Leaders: Tim Clark, PhD, & Sarah Ratcliffe, PhD

The Data Management and Statistical Core (DMSC) enables and accelerates Alzheimer Disease and Related Dementias (AD/ADRD) research, using the most up-to-date methods of the rapidly evolving disciplines comprising Biomedical Data Science. It is foundational in building the Virginia Alzheimer Disease Center (VADC) and will make its methods and outputs available to research collaborations nationally and internationally. The DMSC is a “launch pad” for introducing advanced data science methods and infrastructure to accelerate AD/ADRD research as a foundation for all VADC Cores, and will share methods and collaborate with other Centers. 

The DMSC manages day-to-day operational data of the VADC across Cores, sharing subject cohort data securely with the National Alzheimer’s Coordinating Center, and will manage submission of neuroimaging data to SCAN. It provides world-class expertise and tools in biomedical data science to promote new AD/ADRD research projects at the University. 

This includes a Virginia Dementia Commons Environment (VDCE), based on the UVA FAIRSCAPE instance and FAIRSCAPE extended AI-Readiness tools and frameworks developed in the NIH Bridge2AI program, on which the Core leads serve as co-PIs.  FAIRSCAPE is a computational data lake where investigational data, software tools, and computational results, can be found and shared by authorized researchers, and directly cited in research publications. Its Bridge2AI-based AI-Readiness tools provide machine-readable detailed descriptions of all stages of data preparation as a foundation for pre-model AI explainability. 

The DMSC will continue to work closely with the Research Education Core, to provide training in advanced data science methods to Center-affiliated researchers. 

Core Leader: Jim Mandell, MD, PhD

The Neuropathology Core performs critical work necessary for validation and translation of basic research.  Collection of human biospecimens is an essential step towards developing better diagnostic tools and therapies for neurodegenerative disorders. The Core provides state-of-the-art neuropathological autopsy diagnostic evaluations and collects brain tissue specimens that are representative of diverse and historically underrepresented populations suffering from neurodegenerative disorders. The Core maintains a repository of well-characterized and clinically annotated  tissue samples. Within the VADC ecosystem, our Core bidirectionally connects to all the other Cores within the center. For example, the Neuropathology Core receives specimens from and provides results to the Clinical Core as well as receives validated biomarkers from and provides specimens to the Biomarker Core. The Core also facilitates collaborative projects within the Basic Science Core and engages with the Research Education Component in several formal and informal teaching environments.

Core Leader: Ishan Williams, PhD

The Outreach, Recruitment, and Engagement Core (OREC) works to build community awareness and educational opportunities for patients and their family care partners related to Alzheimer’s disease and Related Dementias (ADRD), cognitive aging, and research through the Virginia Alzheimer’s Disease Center (VADC). The OREC develops key outreach and engagement opportunities to improve access to ADRD education and clinical trials. The OREC actively engages underserved and marginalized community members in community-based solutions and focused outreach efforts to reduce health inequities and improve quality of life. Despite the prevalence of higher rates of Alzheimer’s disease among Black adults, research participation and postmortem examinations in this population continues to remain low, particularly among those from rural locales. This underscores the need for valid and reliable research from diverse cohorts with varying levels of education and SES to determine if there are unique within group differences in the characteristics and mechanisms of cognitive aging and the trajectory of ADRD.  The recruitment of Black adults, and or rural adults, for clinical research studies is a well-established barrier in research that has limited the generalizability of research findings and perpetuated a degree of uncertainty regarding the etiology and risk for ADRD.  Recruitment of rural and historically underrepresented populations is an even greater challenge. As such, the OREC is making a concerted effort to create culturally sensitive materials and programming in which the development and delivery are informed by members of the community the OREC will serve. The OREC of the VADC at the University of Virginia (UVA) is invested in increasing the representation of rural and Black patients and care partners in research, as well as providing evaluation and follow-up to patients and control subjects followed in the Clinical Core and enrolled in the participant registry. Specifically, the OREC provides a detailed evaluation of the outreach and engagement efforts to increase awareness of AD, recruitment into participant registries, and interprofessional training and education to students, healthcare professionals, and community advocates. The Core strives to assess and address how ethical, historical, social, economic, socio-cultural, and contextual factors serve as barriers to the treatment or management of AD, especially in mistreated, underrepresented, or underserved communities. We will also establish the VADC as a model for minority recruitment and central resource for AD research, support, and training within the state, region, and country.  

Core Leaders: Meghan Mattos, PhD, & Jack Van Horn, PhD

The goal of the Virginia Alzheimer’s Disease Center (VADC) Research Education Component (REC) is to provide enriching and comprehensive research education opportunities to a spectrum of young investigators with interests in building careers in Alzheimer’s Disease (AD) research. Under the VADC REC Scholars program, we actively recruit, cultivate, and support post-doctoral and clinical research associates, and junior faculty by leveraging the interdisciplinary and collaborative nature of UVA faculty in the VADC and its related programs. Carefully identified young researchers from across varied scientific domains and extant research training programs at UVA including training in the foundations of AD neurobiology, clinical neurology, care partner health, and data science techniques. A particular emphasis is placed on recruiting women and under-represented minorities to our VADC REC program. Each VADC Scholar is strategically partnered with a specifically-selected set of VADC Core faculty mentors to supervise their AD research education. VADC Post-Doctoral and Clinical Scholars receive hands-on research training in AD-related research approaches in association with VADC Core mentors and their teams. VADC Faculty Scholars broaden their collaborative networks through engagement with the VADC Cores, contribute to active research, etc. All VADC Scholars take part in virtual and in-person skills training activities, are exposed to examples and means for effective collaborative research practice, understand sources of research funding, and the generation of innovative ideas for team research projects. Opportunities are provided for maximal career development, taking next steps in AD/ADRD research, and research independence. The VADC REC works closely with the VADC Outreach, Recruitment & Engagement Core to attract participants from HBCU institutions in Virginia, to offer community-focused workshops and seminars relevant to AD/ADRD, showcasing the outcomes of VADC research studies, and featuring a guest speaker series. The highlight of the VADC REC program is a rigorous and interactive 3-day workshop for all stakeholders, held each spring, featuring a review of VADC activities, responsible research practice, team building, instruction in data science resources, manuscript, and seed grant proposal development sessions. The VADC REC rigorously assesses the progress of individual VADC Scholars through the program, the effectiveness of its research training activities, and the long-term career paths of past VADC Scholars. With a well-suited VADC REC team, leadership structure, and a track record of prior success, ours is a novel program for ADRD research training and community building, fully aligned with the goals of the NIA P30 program.