The Alzheimer’s Disease Research Center (ADRC) at Wake Forest School of Medicine brings together the latest technologies in neuroscience, neuropsychology, brain imaging and new treatments—all helping to find new ways to slow brain aging. The ADRC studies the role of metabolic and vascular risk factors in promoting the transition from normal aging to mild cognitive impairment, and then to Alzheimer’s or other forms of pathological brain aging such as vascular cognitive impairment (VCI). Our researchers aim to delay, prevent and ultimately cure Alzheimer’s disease and other dementia disorders.
Specifically, the Wake Forest ADRC provides infrastructure for translational, interdisciplinary research on the pathophysiology, prevention and treatment of Alzheimer’s disease and related disorders. Our ADRC focuses on the transition from normal aging to mild cognitive impairment and then to Alzheimer’s disease and other dementias, with emphasis on understanding the contribution of metabolic and vascular factors to these transitions. The ADRC is enrolling a diverse group of adults to facilitate the discovery of new biomarkers and promising targets for prevention and therapy. We also are using novel nonhuman primate models to promote pivotal mechanistic and translational research. Finally, we are educating new investigators in translational research practices, and educating health professionals, afflicted adults, their families and their communities about Alzheimer's disease and strategies for reducing risk. The ADRC orchestrates these efforts through seven integrated Cores.
The Administrative Core is led by Suzanne Craft, PhD, (ADRC PI) and co-led by Jeff Williamson, MD, MHS, and Laura Baker, PhD (Associate Directors). The Administrative Core ensures that ADRC goals are achieved by providing oversight, governance and scientific direction to the Center. Executive Committee members include Drs. Suzanne Craft, Laura Baker, Jeff Williamson, Stephen Kritchevsky, Mark Espeland, Steve Rapp, Kathleen Hayden, Tim Hughes, Carol Shively, Tom Register, Chris Whitlow, Sharon Letchworth, Thomas Montine (Stanford University) and Dr. Dirk Keene (University of Washington). The Executive Committee integrates input regarding scientific, educational and other programmatic missions from the Cores, Internal Advisory Committee, External Advisory Committee and Community Advisory Board.
In addition, the Committee for Resource Utilization and Research Expansion (CRUX) establishes key metrics for funding, publication, education, resource distribution and recruitment. This committee guides the referral of clinical trial participants to research studies locally and nationally and the distribution of data and biospecimens for studies worldwide. The CRUX committee helps integrate the Wake Forest ADRC into the national Alzheimer’s Disease Center (ADC) network, the National Alzheimer’s Coordinating Center (NACC) and the National Cell Repository for Alzheimer’s Disease (NCRAD), thus enhancing its scientific impact through collaborative exchange of resources and ideas.
Finally, the Pilot Grant Committee oversees the solicitation of applications and selection of pilot grant awards for early-career investigators and new Alzheimer’s disease researchers. ADRC pilot grants help Wake Forest investigators generate preliminary data to expand their extramural funding.
The Clinical Core studies the role of metabolic and vascular risk factors in promoting the transition from normal aging to mild cognitive impairment, and then to Alzheimer’s or other forms of pathological brain aging such as vascular cognitive impairment (VCI).
The Clinical Core, led by Jeff Williamson, MD, MHS, and Suzanne Craft, PhD, is establishing a well-characterized cohort, called the Healthy Brain Study, of approximately 500 people consisting of cognitively normal adults, adults with mild cognitive impairment (MCI) and patients with early Alzheimer’s disease with different metabolic risk profiles to participate in ongoing clinical trials. The Core will maximize the participation of African American adults and others from diverse racial and ethnic backgrounds who have higher rates of metabolic and vascular disease and dementia. In addition, it will create a powerful data and biospecimen repository available to the National Alzheimer’s Coordinating Center (NACC), the National Cell Repository for Alzheimer’s Disease (NCRAD) and Alzheimer’s disease investigators worldwide for innovative translational research.
The interdisciplinary Clinical Core team includes geriatricians, neurologists, neuropsychologists, neuroradiologists and other experts to evaluate metabolic and neurologic disease. The Clinical Core coordinates recruitment efforts with the Outreach Core; aligns key measures and combines biospecimens and data with the MESA Core; provides biospecimens to the Neuropathology Core; and provides data (clinical, cognitive and imaging) to the Data Management and Data Analytics Core. The Clinical Core provides innovative methods, a unique cohort and an extensive repository of data, imaging and biospecimens that will enable numerous studies to accelerate our understanding of the earliest stages of Alzheimer’s disease and other forms of pathological brain aging.
The Data Management and Data Analytics (DMDA) Core is led by Mark Espeland, PhD, and and co-led by Iris Leng, MD, PhD. The mission of the DMDA Core is to provide outstanding data management, biomedical computing and analytical collaboration to ADRC investigators and affiliates and to provide high-quality standardized research data. The DMDA Core collaborates with other Cores on the dissemination of Wake Forest ADRC study findings and the engagement of diverse cohorts.
The DMDA Core maintains state-of-the-art resources for data management, study management and reporting to ensure the highest data quality and study integrity and to increase the efficiency and impact of ADRC research. We will leverage our leadership in the coordination of major studies of dementia and cognitive decline with large numbers of adults with high-risk metabolic and vascular disease profiles. This synergy permits the efficient development of studies to assess both potential mechanisms affecting the risk of Alzheimer’s disease and the clinical impact of promising therapeutic strategies.
The DMDA Core provide methodological and analytical expertise in study design, biostatistics and other analytical sciences (including measurement, image analysis, modeling, computational biology, statistical genetics, precision medicine and biomathematics) to ADRC projects. The Core uses state-of-the-art and novel analytical methods to mine our data resources from major studies of cognition and Alzheimer’s disease, to facilitate efficient study design, to provide a platform for pooled analyses and to provide resources to foster the development of Alzheimer’s disease researchers. The Core also develops and maintains efficient and secure platforms for data exchange within the Wake Forest ADRC and with the National Alzheimer’s Coordinating Center (NACC), National Cell Repository for Alzheimer’s Disease (NCRAD), the national Alzheimer’s Disease Center (ADC) network and Alzheimer’s disease researchers. These efforts ensure that the Wake Forest ADRC research programs are designed and conducted according to thoughtful and rigorous standards and that data are vigorously explored and appropriately shared.
The Multi-Ethnic Study of Atherosclerosis (MESA) Core, co-led by Tim Hughes, PhD, Stephen Rapp, PhD, and Kathleen Hayden, PhD, will follow a diverse group of older adults (45 percent African American) for whom metabolic/cardiovascular status has been intensively characterized since 2000. The MESA Core will identify early markers of risk and share data and biospecimens with Wake Forest ADRC researchers, the National Alzheimer’s Coordinating Center (NACC), the National Cell Repository for Alzheimer’s Disease (NCRAD) and Alzheimer’s disease investigators worldwide.
The parent MESA study is an NIH-supported multi-site study of subclinical and incident vascular and metabolic disease. Wake Forest is one of six MESA clinical sites, which provides a unique opportunity for partnership with the ADRC. The Wake Forest site cohort currently consists of approximately 400 adults (47 percent African American, 54 percent women) who have been monitored at regular intervals since 2000. Participants now range from 58 to 97 years of age and are within the window for onset of later-life cognitive impairment and dementia. Participants have undergone extensive metabolic phenotyping such as fasting glucose, insulin, hemoglobin A1C, lipid particle size, plasma lipidomic and metabolomic analyses; vascular phenotyping such as arterial stiffness, coronary artery calcification and carotid ultrasound; whole genome and exome sequencing and epigenetic characterization; repeated retinal imaging; and a brief cognitive assessment.
To this rich array of data, the Wake Forest ADRC will add more extensive clinical and cognitive assessment (Uniform Data Set and supplemental cognitive tests); neuroimaging (magnetic resonance imaging, amyloid positron emission tomography); and collection of cerebrospinal fluid and brain donations. With these data, we can thoroughly assess cognitive and biomarker trajectories over time and derive clinical/pathological diagnoses of Alzheimer’s disease, vascular cognitive impairment and other disorders. The Wake Forest ADRC MESA Core will leverage extensive, multidimensional data available in the racially diverse and well-characterized MESA cohort to rapidly identify specific vascular and metabolic contributions to Alzheimer’s disease and other dementias.
In 2018, MESA received funding from the National Institute on Aging to extend MESA Core initiatives to all six MESA Field Centers (Wake Forest, Columbia University, Johns Hopkins University, Northwestern University, University of Minnesota and the University of California, Los Angeles). Wake Forest serves as the administrative core for these efforts, led by Timothy Hughes, PhD, Kathleen Hayden, PhD, and Jose Luchsinger, MD, MPH.
The Neuroimaging Core is co-led by Christopher Whitlow, MD, PhD, MHS, and Samuel Lockhart, PhD. This Core enables systematic, longitudinal, multimodal neuroimaging using both magnetic resonance imaging (MRI) and positron emission tomography (PET) of amyloid and tau in intensively characterized, ethnically diverse participants enrolled in the Wake Forest ADRC. The Neuroimaging Core provides state-of-the-art imaging data aligned with other valuable ADRC resources to Wake Forest investigators, to the National Alzheimer’s Coordinating Center (NACC) and to other researchers to enhance the conduct of high-impact research on Alzheimer’s disease. The Neuroimaging Core will also apply human imaging protocols to aged nonhuman primates who develop amyloid pathology and vascular disease to facilitate translational research. In addition, the Core will provide consultation and training regarding imaging methods and scientific advances.
The NIC will leverage valuable clinical data from the unique and diverse Clinical Core and significantly enhance the ADRC’s contribution to the Alzheimer’s Disease Centers network and to investigators worldwide through the following goals:
- Provide a comprehensive research infrastructure that incorporates the latest scientific advances in neuroimaging to enhance our understanding of Alzheimer’s disease, with special imaging resources to investigate metabolic and vascular contributions to early transitions from normal aging to mild cognitive impairment, Alzheimer’s disease and other dementias
- Optimize participation of underrepresented groups in neuroimaging activities, with a special focus on African-Americans, to better understand and reduce disparities in their risk of Alzheimer’s disease and other dementias
- Expand interactions with the Alzheimer’s Disease Centers network, key affiliates such as NACC and institutional partners such as the Pepper Center through aligned neuroimaging methods and new collaborations
- Provide training and consultation regarding the latest scientific advances in neuroimaging to ADRC-affiliated investigators and projects
The Neuropathology Core, led by neuropathologist Thomas Montine, MD, PhD, (Stanford University) and co-led by C. Dirk Keene, MD, PhD, (University of Washington) and Ryan Mott, MD (Wake Forest University), collects, archives and analyzes biospecimens and brain donations from clinical study participants and from nonhuman primate models to build a repository for mechanistic and translational research.
The Neuropathology Core provides resources to support the Wake Forest ADRC focus on early-phase transitions from normal aging to mild cognitive impairment, Alzheimer’s disease, vascular cognitive impairment and related disorders, and the role of metabolic and vascular risk pathways in these transitions. The Neuropathology Core provides state-of-the-art collection, storage and distribution of DNA, blood, cerebral spinal fluid, brain and other biospecimens; establishes neuropathological diagnoses of deceased Clinical and MESA Core participants; and provides resources and expertise for non-human primate and rodent models for pivotal mechanistic and therapeutic Alzheimer’s disease research. The Core builds on Wake Forest’s existing strengths in postmortem diagnosis, as the leading provider of forensic autopsy services in North Carolina, analysis of specialized metabolic and vascular biomarkers, intensively characterized human cohorts, and nonhuman primate models of human disease.
The Neuropathology Core currently maintains a biospecimen repository of DNA, blood and cerebral spinal fluid from more than 1,100 well-characterized participants and will receive and archive biospecimens from ADRC participants in the Clinical and MESA Cores whose metabolic and vascular risk factors put them at high risk for Alzheimer’s disease. DNA is collected for APOE genotyping and genetic analysis and will be provided to National Cell Repository for Alzheimer’s Disease (NCRAD).
Cerebrospinal fluid biomarkers (Aβ, tau, and p181-tau) for Alzheimer’s disease are measured on participants who undergo lumbar puncture, and special expertise is available for biomarkers of metabolic and vascular disease, such as measures of glucose metabolism, neuroinflammation, endothelial dysfunction, lipid/lipoprotein metabolism, metabolomics/proteomics, synaptic function, epigenetic/transcriptomics and mitochondrial function. The Core facilitates distribution of data and specimens in the repository to Wake Forest ADRC and national Alzheimer’s Disease Centers network of investigators, and to NCRAD and Alzheimer’s disease researchers worldwide.
Further, human protocols for specimen collection and neuroimaging have been applied to nonhuman primate models, creating a unique resource with which the Alzheimer’s disease research community can conduct pivotal translational research. We have demonstrated that aged nonhuman primates have neuropathologic changes similar to early Alzheimer’s disease, Alzheimer’s disease-like CSF biomarker profiles, cerebral hypometabolism, brain atrophy and brain mitochondrial abnormalities. Through its unique biospecimen repositories and preclinical models, the Neuropathology Core provides an exceptional resource to investigators engaged in research to discover novel biomarkers and therapeutic targets that impact progression from normal aging to mild cognitive impairment and Alzheimer’s disease or related disorders.
The Outreach and Recruitment Core, co-led by Laura Baker, PhD, and Goldie Byrd, PhD, is the liaison between the Wake Forest ADRC and the community. The Core actively establishes relationships with the community to recruit participants for ADRC studies and provide education and resources for the public. The Outreach Core is recruiting a racially diverse group of research participants, including cognitively normal adults, individuals with mild cognitive impairment at higher and lower risk for cognitive decline and dementia due to metabolic and vascular factors, and adults with Alzheimer’s disease dementia.
The Outreach and Recruitment Core is implementing a program to improve community practices for detection, progression, treatment and prevention of Alzheimer’s disease. The Core works to educate the public and community healthcare professionals about early detection, risk modification, prevention and treatment of mild cognitive impairment, Alzheimer’s disease and related disorders, and to encourage routine clinical screening and treatment practices targeting metabolic and vascular risk modification.
A key educational theme for the Core’s community outreach is the effects of metabolic disease and other vascular risk factors on Alzheimer’s disease onset and progression. Outreach and education for African Americans in North Carolina is a priority, given their high rates of metabolic and vascular disease, and prevalence of Alzheimer’s disease that is two to three times higher than for non-Hispanic white adults. This outreach priority also supports and contributes to escalating national efforts to increase racial and ethnic minority representation in Alzheimer’s disease clinical trials.
The Research Education Component, led by Laura Baker, PhD, and Stephen Kritchevsky, PhD, provides mentoring, training and new research opportunities for early-stage investigators and advances Alzheimer’s disease research for faculty at all stages of career development. The programs will have a translational research focus, particularly with respect to the contributory role of metabolic and vascular risk factors, to bridge the gap between preclinical and clinical development of therapeutic interventions that will prevent, slow and treat Alzheimer’s disease. We leverage Wake Forest resources, including the Claude D. Pepper Older Americans Independence Center, our Clinical and Translational Science Institute and Wake Forest Innovations to support a diverse training curriculum.
This Component draws from Wake Forest’s extensive scientific community to identify key mentors within targeted areas of research and recruits early-stage investigators and other trainees from diverse racial and ethnic backgrounds through multiple Wake Forest Centers and Institutes such as:
- Alzheimer's Disease Research Center
- Sticht Center on Healthy Aging and Alzheimer’s Prevention
- Maya Angelou Center for Health Equity (MACHE)
- Clinical and Translational Science Institute
- Hypertension and Vascular Research Center
- Center for Genomics and Personalized Medicine
- Diabetes Center
- Comparative Medicine/Clarkson Campus
We will conduct a series of “Alzheimer’s Disease 101” workshops which will provide a scientific and clinical overview of Alzheimer’s disease to investigators and trainees to facilitate their research programs in this area. We will also recruit trainees into Research Education Component programs from nearby affiliate academic institutions, including two Historically Black College and Universities (HBCUs) with whom we have established collaborative relationships.