Why the ADCs Were Established

How the ADCs Function Within the NIH Framework

Description of Disease or Condition

Burden of Illness

Scope of NIH Activities: Research and Programmatic

NIH Funding for FY 2006 and FY 2007

Programmatic Accomplishments

• National Alzheimer's Coordinating Center (NACC): Beginning in 1999, the NACC was established to facilitate collaborative research and to standardize procedures among the 29 ADCs. NACC developed and maintains a large relational database of standardized clinical and neuropathological research data collected from each ADC. This database provides a valuable resource to qualified research scientists for both exploratory and explanatory AD research. The data provided by NACC will permit large studies that use patient samples from diverse populations and multiple ADCs. One goal is to standardize procedures among the ADCs in several ways: (1) the approach to diagnosis of AD; (2) the approach to followup with those who have the disease; and (3) the collection of common data elements, also known as the uniform dataset. Although the unique aspects of the individual ADCs will be preserved, a core of common elements will help promote communication among the ADCs as well as with non-ADC researchers and the public. Autopsy confirmation of many of the cases makes these aggregate data especially valuable.
• Alzheimer's Disease Cooperative Study (ADCS): The ADCS is a major AD clinical trials effort that has grown out of the ADC program. This consortium was initially funded in 1991 to test the safety and efficacy of compounds of little interest to large pharmaceutical companies and to evaluate treatments for cognitive and behavioral symptoms of AD. The trials include drugs that are off-patent, were patented and marketed for another use but might be effective in AD, or novel compounds from individual investigators or small companies that lack adequate resources to conduct clinical trials. The ADCS helps to facilitate the testing of new drugs for the treatment of AD and functions as part of the AD Prevention Initiative, which was established to invigorate efforts to discover new treatments, risk factors, methods of early detection, and diagnosis of AD. The ADCS also develops strategies for improving patient care and alleviating caregiver burdens and expedites movement of promising new treatments and prevention strategies into clinical trials. The ADCs serve as performance sites for the ADCS.
• Alzheimer's Disease Neuroimaging Initiative (ADNI): ADNI is an innovative public-private partnership for examining the potential for serial magnetic resonance imaging (MRI), positron emission tomography (PET), or other biomarkers to measure earlier, and with greater sensitivity, the development and progression of mild cognitive impairment and AD. Most ADCs participate in the ADNI. Early results suggest that researchers may be able to reduce the costs associated with clinical trials by improving imaging and biomarker analysis. As part of the ADNI study, a standard physical model (i.e., a plastic phantom) was developed to monitor the performance of MRI scanners at multiple clinical sites, ensuring the accuracy of the MRI images. In another preliminary analysis, investigators compared changes over time in PET scans of brain glucose metabolism in people with normal cognition, mild cognitive impairment, and AD. They found that scans correlated with symptoms of each condition and that images were consistent across sites, suggesting the validity of PET scans for monitoring the effectiveness of therapies in future clinical trials. More than 200 researchers, as well as other interested individuals, have already accessed a public database containing thousands of brain images and related clinical data obtained through blood and cerebrospinal fluid analyses.
• Late-Onset Alzheimer's Disease (LOAD) Genetics Initiative: NIH launched the LOAD Genetics Initiative in 2002 to help advance AD-related genetics research. Eighteen ADCs participate in the initiative. The goal is to collect samples from 1,000 families having at least 2 members with late-onset AD as well as 1,000 control subjects. The Columbia University ADRC serves as the coordination center for the Genetics Initiative. As of 2007, more than 3,000 new blood samples from approximately 400 late-onset AD families have been sent to NCRAD. To complete enrollment, characterization, and followup of patients and control subjects in the Genetics Initiative, NIH awarded a resource grant to a group of six ADCs, which formed a consortium. In 2006, the NIH Center for Inherited Disease Research performed whole-genome scans on approximately 2,500 samples from members of these families. An article based on analysis of these data will be published in summer 2008.
• Overlapping Dementing Diseases: NIA and the National Institute of Neurological Disorders and Stroke (NINDS) are exploring the overlap of Parkinson's disease dementia, dementia with Lewy bodies, and AD, as well as the contributions of cerebrovascular disease to the brain pathology seen in AD. Joint initiatives in these overlap areas are under way. The ADCs collaborate with the NINDS-supported Udall Parkinson's Disease Centers to further the goals of examining the overlapping scientific and clinical issues related to AD, dementia with Lewy bodies, frontotemporal dementia, and Parkinson's disease dementia.
• ADCs Minority Outreach: A major objective for the ADCs is to recruit minority and ethnically diverse research subjects for AD research. A strategy to address this goal was developed in 1990 by creating a program to add Satellite Diagnostic and Treatment Clinics linked to existing ADCs. The number of satellites has fluctuated; 23 are currently active and are recruiting African American, Hispanic, Native American, and Asian research subjects. NACC data now show that approximately 20 percent of those enrolled in the ADCs are minorities.
• Education Outreach: All ADCs have Education and Information Transfer Cores (EITC) that support the development of clinical and research skills related to AD for physicians and other professional staff, as well as outreach to the public, including caregivers. EITC efforts have recently been redefined to emphasize subject recruitment for projects such as the NIA Genetics Initiative, ADCS, ADNI, and other clinical trials and initiatives. Collaborations include ongoing interactions with groups such as the Alzheimer's Association and the NIA's Alzheimer's Disease Education and Referral Center. The ADCs pay special attention to issues of cultural sensitivity, and, where appropriate, the information is structured so it can effectively reach minority populations, including non-English-speaking people. ADCs work with ADEAR to develop materials for broad audiences.
• New York Consortium for Alzheimer's Research and Education (NYCARE): The three New York City ADCs—at Columbia University, Mount Sinai School of Medicine, and New York University—and the New York City chapter of the Alzheimer's Association joined in 2000 to form NYCARE. The consortium provides continuing medical education programs for community physicians on AD diagnosis, management, and research opportunities.
• The Alzheimer's Clinical Research and Training Awards Act: This congressional initiative helps train the next generation of physician-scientists to conduct basic and clinical research on AD and associated dementias. The program provides support for promising clinicians through awards for research, study, and practice at the ADCs. Twelve awards have been made, and most of the awardees are working at ADCs.

Research Accomplishments

• Amyloid-beta Protein Metabolism Studies. Biochemical, genetic, and animal model evidence implicates amyloid-beta as a pathogenic peptide in AD that can lead to abnormal communication among nerve cells and cell death. In late-onset AD, concentrations of this peptide in brain tissue from AD patients are 100- to 200-fold higher than in control brains. Recently, investigators at the Washington University ADC reported a new method for quantifying the synthesis and clearance rates of amyloid-beta in the normal human adult central nervous system. For the first time, investigators can now accurately measure the production and clearance rates of amyloid-beta in the central nervous system of living humans, indicating that under normal circumstances it is rapidly produced and cleared from the central nervous system. This new technique may prove to be of critical importance to scientists in their efforts to address crucial questions about the underlying pathogenesis of AD, to find possible biomarkers, and to test proposed disease-modifying therapies.
• Standards for Assessing Cognitive Status in Understudied Populations: One difficulty in evaluating the cognitive status of people in understudied populations is that the normative values available for standard tests often are not appropriate for other populations. Cultural, linguistic, educational, and other factors differ among groups and consistently have been shown to influence neuropsychological evaluations. Recently, scientists at the Mayo Clinic ADC produced a large set of normative data on older African Americans, using several common neuropsychological assessment tools. The authors note that these normative values may be applicable only to older African Americans raised in the South, making it important to determine whether the new data can be generalized. In addition, over time, even a narrowly defined group might have different characteristics; for example, participants in this sample were educated prior to the Brown vs. the Board of Education decision by the U.S. Supreme Court to end segregation of public school systems. Despite some limitations in its clinical utility, this study represents the first large-scale publication of normative data for an understudied population.
• Establishing Commonalities Between Frontotemporal Dementias and Amyotrophic Lateral Sclerosis: Frontotemporal dementias (FTDs) are a group of neurodegenerative diseases that are sometimes misdiagnosed as AD or related dementing disorders. It is estimated that 35-50 percent of FTD cases have a family history of dementia; nearly half have been linked to a mutation on chromosome 17. In recent studies, researchers have linked some cases of FTD to another mutation on chromosome 17. In addition, a new brain protein has been identified, related to the pathogenesis of both FTD and amyotrophic lateral sclerosis (ALS), in which dementia also can occur. It is thought that changes caused by this mutation impair the ability of the cell to degrade abnormal proteins, thereby causing them to remain in the nervous system, where they contribute to the development of FTD and ALS disease processes. Investigators are continuing to study these proteins and other genetic mutations to further identify and understand the mechanisms involved in the development of FTD, ALS, and other neurodegenerative diseases.

Recommendations for Improving the Effectiveness, Efficiency, and Outcomes of the ADCs

Evaluation Plans

Future Directions