RSNA News - April 2005

Groundbreaking Alzheimer Disease Neuroimaging Trial Begins

We hope to learn which imaging modalities have the greatest power to detect the rates of change in the brain in healthy aging, mild cognitive impairment and the transition to Alzheimer disease.
—Michael W. Weiner, M.D.

Imaging is leading the way in a groundbreaking study designed to establish Alzheimer disease (AD) biomarkers and to better understand AD diagnosis and therapeutic response.

The Alzheimer's Disease Neuroimaging Initiative (ADNI)—a $60 million, five-year public and private partnership—will study the combination of serial MR imaging, positron emission tomography (PET), biological markers, and clinical and neuropsychological assessment in measuring the progression of mild cognitive impairment (MCI) and early AD.

"Imaging is a promising tool for diagnosing early AD and following disease progress and treatment effect," said Susan Molchan, M.D., program director for AD clinical trials at the National Institute on Aging (NIA). "The AD associated changes in the brain happen decades before symptoms are evident. The hope is that eventually, treatments will be developed that can prevent or slow the disease early in its course."

Because of that, time is critical. The seven- to 10-year wait for results of clinical trials is too long. "Markers need to be established now to lessen the cost and time of trials," Dr. Molchan said. "Some of the most promising biomarkers are from imaging."

More than four million Americans have AD and countless others have dementia, resulting in a cost of more than $100 billion annually to the U.S. economy, according to government statistics. By 2025, the incidence of dementia is expected to double.

Although existing treatments are not known to slow the progression of AD, many new therapies are being developed. When effective AD treatments are available, subjects at risk for cognitive decline and dementia will need to be identified at the earliest stage possible.

The information on disease course and biomarkers collected in ADNI are expected to help develop new AD treatments by monitoring their effectiveness. NIA said the project is the most comprehensive effort to date to find neuroimaging and other biomarkers for the cognitive changes associated with mild cognitive impairment and AD.

ADNI will compare neuroimaging, biological and clinical information from 800 participants to find correlations that track memory loss progression from the earliest stages. Approximately 50 sites across the United States and Canada will participate. Enrollment of patients—adults ages 55 to 90 years—begins in mid-May.

"We hope to learn which imaging modalities have the greatest power to detect the rates of change in the brain in healthy aging, mild cognitive impairment and the transition to Alzheimer disease," said ADNI principal investigator Michael W. Weiner, M.D. "We are developing improved methods for imaging in AD clinical trials. ADNI will provide a huge amount of clinical biomarker and imaging data for future analysis."

The ultimate goal, he said, is to establish validated biomarkers for AD treatment trials that will speed conduction of studies and reduce the number of subjects required.

"Most radiologists are involved in looking at scans and making diagnoses," explained Dr. Weiner, who is director of the MR unit at the VA Medical Center in San Francisco and professor of medicine, radiology, psychiatry and neurology at the University of California, San Francisco. "ADNI establishes standards for obtaining images, and all images will be quantitatively measured. Ultimately, radiologists may become more and more involved in quantitative analysis of images, and ADNI is another step in that direction."

Dr. Weiner is urging RSNA members who are located at a site and are involved in imaging research to develop projects that use the ADNI data.

PET scans of a normal brain (left) and an Alzheimer disease brain (right).

View more images

Collaborative Study is First of Its Kind

This type of study is going to be the wave of the future, according to Dr. Molchan. "I think that with many complex diseases we are going to need more than one biomarker," she said. "Heart disease is an excellent example—blood pressure, as well as cholesterol levels, homocystine and C-reactive protein affect risk. We think a battery of tests will be needed to definitively diagnose AD and follow treatment. Neuroimaging is a valuable tool for this type of assessment."

Several pharmaceutical companies, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), Food and Drug Administration (FDA), Alzheimer's Association, Institute for the Study of Aging, and the National Institutes of Health (NIH) Foundation have partnered with NIA on the initiative. The NIH Foundation has received more than $20 million in corporate commitments for ADNI. The federal government is funding about two-thirds of the study and private partners will fund the remaining third. Additional NIH grants will fund ancillary studies.

"The public/private partnership component is important," said Dr. Molchan. "We have been very happy with it and think it's a great model for public/private partnership. We've been working with pharmaceutical companies, universities, the FDA and NIH to get everyone in this field involved in the neuroimaging initiative."

NIBIB Deputy Director Belinda Seto, Ph.D., agreed about the importance of the partnership. "ADNI has a component on neuroimaging that lends itself to this institute's expertise and mission, which is focused on biomedical imaging. NIBIB does not have an emphasis on clinical trials or large-scale human subject studies. We are typically involved in technology development and may support research in early phase feasibility studies."

Dr. Seto said NIBIB is reaching out to other institutes and research communities to partner and leverage resources—both intellectual and material—to do things that NIBIB cannot do on its own.

For more information on ADNI, go to www.loni.ucla.edu/ADNI.