What is the Alzheimer's Disease Neuroimaging Initiative?
The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a $60 million, 5-year public-private partnership to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD).
Why study neuroimaging?
The study will compare neuroimaging, biological and clinical information from study participants seeking correlations among the data that will track the progress of memory loss from its earliest stages. Neuroimaging research has suggested that PET or MRI may serve as a more sensitive and consistent measure of disease progression than the neuropsychological and cognitive assessments now typically used in research. Ultimately, standardizing the methodology for neuroimaging could provide a better way to compare results from different trials and studies, a major goal of the Initiative.
What do scientists hope to learn from the ADNI?
What is learned from the study will be used to help researchers and clinicians develop new treatments and monitor their effectiveness, increasing safety and efficiency of drug development by decreasing the time and cost of clinical trials. The project is the most comprehensive effort to date to find neuroimaging and other biomarkers for the cognitive changes associated with MCI and AD.
Where will the study occur? How many participants will be involved?
The study will take place at approximately 50 sites across the U.S. and Canada. In April 2005, investigators will begin recruiting about 800 adults, ages 55 to 90, to participate in the research—approximately 200 cognitively normal older individuals to be followed for 3 years, 400 people with MCI to be followed for 3 years, and 200 people with early AD to be followed for 2 years.
Who are the Principal Investigators?
A grant to fund the project was awarded to the Northern California Institute for Research and Education (NCIRE), a foundation affiliated with the Department of Veterans Affairs. Michael W. Weiner, M.D., of the Veterans Affairs Medical Center in San Francisco and the University of California at San Francisco, is Principal Investigator for the Initiative. A Coordinating Center for the nationwide, multi-site study will be located at the University of California at San Diego under the direction of Leon J. Thal, M.D.
NIA scientists directly responsible for the Initiative are Neil Buckholtz, Ph.D., head of the Dementias of Aging Branch, Susan Molchan, M.D., head of the Alzheimer's Disease Clinical Trials Section, and Marcelle Morrison-Bogorad, Ph.D., an Associate Director of the NIA who leads the Neuroscience and Neuropsychology of Aging Program.
How can I volunteer?
While recruitment for the study will not begin until spring 2005, people interested in participating in the study can contact the NIA's Alzheimer's Disease Education and Referral (ADEAR) Center at 1-800-438-4380 for additional information.
What is mild cognitive impairment and how does it differ from Alzheimer's disease?
AD is an irreversible disorder of the brain, robbing those who have it of memory, and eventually, overall mental and physical function, leading to death. It is the most common cause of dementia among people over age 65, affecting an estimated 4.5 million Americans. MCI differs from both AD and normal age-related memory change. People with MCI have ongoing memory problems but not to the point where their impairment interferes significantly with daily activities.
What are biomarkers and why are they important in this study?
A biomarker is a biochemical indicator that can be used to measure the progress of disease or the effects of treatment. High cholesterol levels, for instance, are a biomarker for heart disease. PET scans of people with AD show that glucose in certain parts of the brain is metabolized at lower levels than in healthy people, and previous studies have shown that low glucose metabolism can be seen in some people even before noticeable symptoms of memory loss occur.
Other research indicates that biological factors from blood, cerebrospinal fluid (CSF), and urine samples may be markers for dementia. ADNI researchers will be looking at a number of potential markers including levels of beta-amyloid and tau, components of the plaques and tangles considered to be the hallmarks of AD; indicators of inflammation such as C-reactive protein and alpha-anti-chymotrypsin; measures of oxidative stress such as oxysterols and isoprostanes; and genes that are associated with increased risk for AD.
Identifying such biomarkers could help scientists accurately monitor disease progression and detect the effects of treatments which can slow that progression.
How will the study be funded? Who is participating in the public-private partnership?
Within the Federal Government, the NIA is joined in the partnership by another NIH Institute—the National Institute of Biomedical Imaging and Bioengineering (NIBIB)—and the Food and Drug Administration, all of which are part of the U.S. Department of Health and Human Services. The Foundation for NIH is managing corporate and other private participation, and has received commitments totaling more than $20 million in contributions from the following companies and organizations: Pfizer Inc, Wyeth Research, Eli Lilly and Company, Merck & Co, Inc., GlaxoSmithKline, AstraZeneca AB, Novartis Pharmaceuticals Corporation, Eisai Global Clinical Development, Elan Corporation, plc, the Institute for the Study of Aging (ISOA), and the Alzheimer's Association. About two-thirds of the funding is expected to come from the Federal Government, while private partners are expected to make up the other third. Ancillary studies will be funded by additional NIH grants.
Why are pharmaceutical companies participating in this study?
The Initiative is built on basic scientific discoveries that have advanced our understanding of AD pathophysiology and genetics. With this new knowledge have come opportunities for the development of several new compounds designed to interfere directly with mechanisms of the disease in order to slow it down or stop its progression entirely. Pharmaceutical companies involved in the study believe that development of imaging measures and other biological markers may help to rapidly identify appropriate doses, assess safety, and allow for comparisons among drugs, as well as to evaluate the effects of drugs on disease progression.
What can you tell us about the organizations involved in the study?
The National Institute on Aging leads the Federal effort in research on AD and age-related cognitive change. The Institute is currently funding 6 prevention trials and 19 treatment trials for AD, in addition to the Neuroimaging Initiative. For more information on participation in an AD clinical study, visit www.clinicaltrials.gov (search for "Alzheimer's disease" trials), or visit the ADEAR Center website at www.alzheimers.org. The public and health professionals may also contact ADEAR toll free at 1-800-438-4380. The ADEAR Center is sponsored by the NIA to provide information to the public and health professionals about AD and age-related cognitive change.
The National Institute for Biomedical Imaging and Bioengineering is the newest of the research institutes at the NIH, established in 2000. Its mission is to improve health by promoting fundamental discoveries, design and development, and translation and assessment of technological capabilities. The Institute coordinates with biomedical imaging and bioengineering programs of other agencies and within NIH. More information on NIBIB may be found at www.nibib1.nih.gov.
The Foundation for the National Institutes of Health was established by Congress to support NIH research and its activities. A non-profit, 501(c)(3) corporation, the Foundation has been a leading force at NIH in helping to build public-private partnerships to accelerate scientific discovery and the development and delivery of health interventions. More information on the Foundation is available at www.fnih.org.
The Institute for the Study of Aging, a private New York-based foundation endowed by the Estee Lauder Trust, encourages and supports the discovery and development of new therapies to prevent and treat AD. More information on the ISOA can be found at www.aging-institute.org.
The Alzheimer's Association funds AD research and also provides information on clinical trials and the disease. The Association is a private national advocacy organization for families and patients with AD. The Association's website is www.alz.org.
What else do I need to know about the study?
Other important aspects of the project include:
- A data sharing requirement that clinical, imaging, and biological data collected will be made available promptly to all qualified scientific investigators in the public and private sector, whether they are part of the study or not.
- A Coordinating Center to manage the tracking of all subject recruitment and visits, including clinical/neuropsychological assessment, MRI and PET scans, blood/CSF collection, genotyping, data quality assurance/quality control, and transmission, storage, and assurance of confidentiality of data. UCSD's Dr. Thal will build upon his management of the NIA-supported Alzheimer's Disease Cooperative Study (ADCS), a national consortium of academic medical centers, and other researchers, who are already conducting a number of multi-site clinical studies. Ronald Petersen, M.D., Ph.D., Mayo Clinic, Rochester, will help direct clinical aspects of the study.
- "Cores" are set up to manage specific parts of the project. Within a Neuroimaging Core, two investigators will direct sections as follows: MRI led by Clifford Jack, M.D., Mayo Clinic, Rochester, MN, and PET by William Jagust, M.D., University of California, Berkeley. A Biomarkers Core will be directed by John Trojanowski, M.D., University of Pennsylvania, Philadelphia. An Informatics Core will be directed by Arthur Toga, Ph.D., University of California, Los Angeles, and a Biostatistics group will be headed by Laurel Beckett, Ph.D., University of California, Davis. Ron Thomas, Ph.D., of UCSD will lead the Informatics group within the AD Neuroimaging Intiative Clinical Core, which will have responsibility for management of both the ADNI Clinical and Biomarker datasets.
- A Steering Committee made up of investigators and representatives from all the partners in the Initiative will guide the study. An External Scientific Advisory Committee comprised of distinguished researchers will also monitor the progress of the study and provide oversight and additional input from a wide range of experts. The Steering Committee will be headed by Dr. Weiner and the Advisory Committee by Zaven Khachaturian, Ph.D., Senior Science Advisor, Alzheimer's Association.
Will this study have any influence on Medicare funding of neuroimaging?
In September 2004, the Centers for Medicare and Medicaid Services decided to expand Medicare coverage of PET on a limited basis to include beneficiaries who meet the diagnostic criteria for both AD and fronto-temporal dementia, who have been evaluated for specific alternate causes of dementia, and for whom the cause of the clinical symptoms remains uncertain, and for patients in certain large clinical trials. Studies such as the AD Neuroimaging Initiative and other research should help determine the value of PET scans for the broader Medicare population. For more information on Medicare coverage, visit the CMS website at www.cms.hhs.gov/coverage.