Alzheimer's Disease Neuroimaging Initiative (ADNI)
Long Name: Alzheimer's Disease Neuroimaging Initiative (ADNI)
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).
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 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.
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.
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.
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.
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.
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.
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.