Centers of Excellence
Alzheimer’s Disease Centers
Based on concerns about the enormity of the problems posed by Alzheimer’s disease, Congress directed NIH to foster further research related to Alzheimer's disease (AD) in the Public Health Service Act of 1984. Under section 445 of this act, Congress authorized the establishment of the NIH Alzheimer’s Disease Centers (ADCs) program. (42 U.S.C. 285e-2). The first ADCs were established through NIH funding in the mid-1980s in response to the congressional directive, information on AD emerging from the work of NIH grantees and other researchers, and the prospect of a medical and social crisis triggered by an explosion of AD cases due to population aging. The principal objectives of the ADC program are to conduct cutting edge basic, clinical, translational, and social/behavioral research; train the next generation of researchers; and provide information to the public about research findings, access to support services, and opportunities to participate in research. Much of the research takes place through multicenter cooperative studies to better understand the causes and effects of AD and to develop and test new interventions for the diagnosis, treatment, and prevention of AD and other age-related neurodegenerative diseases.
NIH currently funds 27 ADCs (see Table 4-1). Funding for the ADCs comes from NIA through the P30 (center core grant) and P50 (specialized center grant) mechanisms for five years; centers compete through a peer review process for additional funding. New applicants for ADC funding compete with existing grantees.
AD is the most common form of dementia among older people. It is an age-related, irreversible brain disorder that develops over many years. In the earliest stage, people experience memory loss or other, usually mild, behavioral or cognitive changes; these are sometimes mistaken for changes that may occur during the normal aging process. As the disease progresses however, these symptoms gradually lead to dementia, a condition characterized by marked memory loss accompanied by behavior and personality changes. The disease also leads to a decline in other cognitive abilities (such as decision-making and language skills) and eventually to an inability to recognize family and friends and severe mental decline. These losses are related to the breakdown of the connections between neurons in the brain and the eventual death of many of these cells. For most people who develop AD, symptoms first appear after age 65. AD and other dementing disorders are caused by disease processes that affect the brain, although age-related brain and body changes also can affect the timing and progression of AD and other dementias.
AD probably has no single cause. The most important known risk factors for the development of AD are age and family history, although education, diet, and environment appear to play a role. Scientists also are finding evidence that some of the risk factors for heart disease and stroke—such as high blood pressure, high cholesterol, and low levels of the vitamin folate—might increase the risk for AD. Increasing evidence also suggests that physical, mental, and social activities may help to delay the onset of AD. Although scientists have learned a great deal about AD, they still do not know what causes the disease and have not identified a cure.
Recent estimates from a nationally representative sample in the Aging, Demographics, and Memory Study (part of the ongoing NIH-supported Health and Retirement Study) suggest that one in seven Americans age 72 or older has dementia and about 2.4 million have AD. Other investigators, using projections from community-based studies, estimate that 5.1 million Americans ages 65 or older have AD. Despite the differing methodologies and results of their studies, experts agree that the number of people with AD will increase significantly if current U.S. demographic trends continue and no effectiveprevention methods emerge. Our aging society makes AD an especially critical issue because the number of people with the disease doubles for every five-year age interval beyond age 65. The U.S. Census Bureau estimates that the size of the population ages 65 and older will increase to about 72 million people in the next 25 years. Moreover, the fastest growing segment of the U.S. population consists of people 85 years of age or older.
The ADC program provides infrastructure and core resources to enhance ongoing research by bringing together basic biomedical, behavioral and social, and clinical scientists to study the causes, progression, prevention, diagnosis, and treatment of AD and to improve health care delivery. ADCs also foster the development of new research approaches and provide training opportunities for research fellows and junior faculty interested in conducting interdisciplinary AD research. By pooling resources and working cooperatively with other ADCs, these centers have produced research findings and developed resources that would have been impossible for investigators working alone.
The ADC program includes two types of centers. NIH requires all ADCs to contain administrative, clinical, data management and statistics, education and information transfer, and neuropathology components, known as “cores,” and some Centers support other cores providing specialized resources such as neuroimaging or genetic data. The eleven Alzheimer’s Disease Core Centers provide investigators within and outside the ADC program with access to the broad spectrum of ADC resources, while 16 Alzheimer’s Disease Research Centers conduct research projects in addition to providing core resources. Some Centers also support satellite diagnostic and treatment clinics to help recruit from underrepresented groups.
Resources shared among ADCs include brain and specimen banks at each center, which consist of well-characterized specimens collected under standardized protocols; ADCs have provided biological samples from patients with AD for hundreds of non-ADC funded projects.
A major resource shared by the ADCs is the National Cell Repository for Alzheimer’s Disease (NCRAD) at Indiana University, which collects and stores blood, DNA, and cell lines from families with several members affected by AD and from unaffected control participants. NCRAD also stores well-documented phenotypic data, including age and gender. The repository is part of the NIH Alzheimer’s Disease Genetics Initiative, which was established to identify genetic risk factors for late-onset AD, and the recently funded Alzheimer’s Disease Genetics Consortium (ADGC), which conducts large-scale whole-genome studies on AD. The ADGC itself maintains one of the largest collections of samples available for genome-wide association studies of Alzheimer’s disease that are being used to identify the susceptibility and protective genes influencing the onset and progression of late-onset disease. These samples are especially valuable because of the rich associated clinical data also available for each participant.
The ADCs have helped create additional collaborative research resources or projects such as the National Alzheimer’s Coordinating Center, the Alzheimer’s Disease Cooperative Study, and the Alzheimer’s Disease Neuroimaging Initiative. Descriptions of these and other efforts are provided in the following section.
Much of the important progress in AD research in the U.S. during the past 28 years stems from research conducted at or resources provided by the ADCs. ADC scientists have conducted a significant amount of the research on protein processing related to plaque and tangle formation in the brain, hallmarks of Alzheimer’s disease. ADC researchers also have identified the common properties of the abnormal proteins associated with several neurodegenerative diseases. In recent years, ADC researchers have evaluated cognitive changes associated with normal aging and the transitions to mild cognitive impairment (early difficulties with thinking and remembering) and dementia. With that has come a more precise understanding of the timing of various types of cognitive changes as well as the development of better ways to measure and evaluate those changes. They also have identified factors that contribute to changes in cognitive abilities such as social and physical activity.
Currently, many ADCs are carrying out important studies relating changes in brain structure to the clinical stages of AD. For these studies, researchers are examining patients enrolled in the clinical cores, brain imaging supported by imaging cores, and autopsy evaluations from the neuropathology cores. ADC researchers also are examining relationships and commonalities between AD and cerebrovascular disease or other neurodegenerative diseases as well as contributions of co-existing non-neurological conditions that occur in people with AD. In addition, the ADCs are exploring commonalities between AD and other dementias, including Parkinson’s disease dementia. In this regard, collaborations are underway with the NINDS-supported Udall Parkinson’s Disease Centers to examine many overlapping scientific and clinical issues.
Another major objective for the ADCs is to recruit minority and ethnically diverse research participants for AD research. To achieve this goal, NIH created the Satellite Diagnostic and Treatment Clinics and linked them to the ADCs. Currently there are 18 active Satellite Clinics recruiting African American, Hispanic, Native American, and Asian participants. National Alzheimer’s Coordinating Center data now show that approximately 20 percent of those enrolled in the ADCs are minorities. Also, the ADCs conduct research related to specific minority concerns in cooperation with the NIH-supported Research Centers on Minority Aging Research.
All ADCs have Education and Information Transfer Cores (EITCs) that provide research training for new investigators, as well as outreach to the public, including caregivers. EITC efforts also have been redefined recently to facilitate participant recruitment for large scale, national projects such as the NIA Genetics Initiative, Alzheimer’s Disease Cooperative Study, Alzheimer’s Disease Neuroimaging Initiative, and other clinical trials and initiatives. Collaborations include ongoing interactions with organizations such as the Alzheimer’s Association, Administration on Aging, and NIH’s Alzheimer’s Disease Education and Referral Center. The ADCs pay special attention to issues of cultural sensitivity and, where appropriate, structure their information to effectively reach minority populations, including non-native English speakers people.
NIH funding for the ADCs was $50.55 million in FY 2010 and $49.76 million in FY 2011 for non-ARRA (regular appropriations), and $10,000 in FY 2010 for ARRA appropriations.
Programmatic accomplishments for the ADCs include the following examples.
In 2012, the ADCS renewal application will be submitted and reviewed. Building on recent exciting discoveries from the Alzheimer’s Disease Neuroimaging Initiative, the ADCS will focus on new trial approaches using imaging and other biomarkers in cerebrospinal fluid and plasma to identify participants with AD pathology and to track disease progression and treatment response. ADCS investigators will also place an increased emphasis on prevention studies, particularly in at-risk but presymptomatic individuals.
In 2009, Recovery Act funding enabled the ADNI study to move into the “ADNI GO” phase. The ADNI GO research effort is the first of its kind to focus on participants who exhibit the earliest signs of memory loss in mild cognitive impairment, thought to be a precursor to AD. While the ADNI GO project work continues, the overall ADNI effort is rapidly moving into a third phase, known as “ADNI 2,” which has built upon the successes of earlier ADNI phases to identify the earliest signs of Alzheimer’s disease.
Since the establishment of the ADC program in 1984, investigators have published thousands of research papers on all aspects of AD and related disorders. Topics have ranged from the disease’s biology to its family and societal impact, as well as many studies of diagnosis and treatment.
Research accomplishments include the following important recent studies carried out by ADC scientists, which highlight research on biomarkers and AD recently carried out by several centers. These studies are only a few examples from a wide spectrum of research studies conducted by the ADCs.
The National Advisory Council on Aging evaluates and makes recommendations for the ADC program every four years. The next evaluation is scheduled for 2013.
NIH plans for the ADCs to continue to emphasize research related to the transition from normal aging to mild cognitive impairment and to full-blown AD, as well as on studies of the overlap between AD and other neurodegenerative diseases instead of concentrating on late-stage AD . In addition, the ADCs will continue to search for biomarkers that predict cognitive decline and diagnose cognitive impairment and dementia.
|Institution and Location||Year Established|
|University of California, San Diego, CA||1984|
|Massachusetts General Hospital, Boston, MA||1984|
|Mount Sinai School of Medicine, New York, NY||1984|
|University of Southern California, Los Angeles, CA||1984|
|Johns Hopkins University, Baltimore, MD||1984|
|University of Kentucky, Lexington, KY||1985|
|University of Pittsburgh, Pittsburgh, PA||1985|
|University of Washington, Seattle, WA||1985|
|Washington University, St. Louis, MO||1985|
|University of Texas Southwestern Medical Center, Dallas, TX||1988|
|Columbia University Health Sciences, New York, NY||1989|
|Oregon Health & Science University, Portland, OR||1990|
|New York University School of Medicine, New York, NY||1990|
|Mayo Clinic College of Medicine, Rochester, MN||1990|
|University of Pennsylvania, Philadelphia, PA||1991|
|University of California Davis School of Medicine, Sacramento, CA||1991|
|Indiana University, Indianapolis, IN||1991|
|Rush University Medical Center, Chicago, IL||1991|
|University of California, Los Angeles, CA||1991|
|Boston University Medical Campus, Boston, MA||1996|
|Northwestern University, Chicago, IL||1996|
|University of California, Irvine, CA||1996|
|Arizona Alzheimer’s Center, Phoenix, AZ||2001|
|University of California, San Francisco, CA||2004|
|Emory University, Atlanta, GA||2005|
|University of Wisconsin, Madison, WI||2009|
|University of Kansas Medical Center, Kansas City, KS||2011|