A new imaging molecule that can detect and map plaques and tangles in the brains of people with Alzheimer's disease could eventually lead to earlier diagnosis of the devastating disease, researchers at the University of California, Los Angeles report in the Dec. 21, 2006, issue of the New England Journal of Medicine. The compound, developed by UCLA and called FDDNP, also holds promise as a research tool to evaluate new treatments for Alzheimer's. The study was funded in part by the National Institute on Aging (NIA), one of the National Institutes of Health (NIH).
FDDNP binds to plaques and tangles, enabling researchers to see these abnormal deposits that form in the brains of people with Alzheimer's disease on PET (positron emission tomography) scans. PET scans display maps of the brain that scientists use to understand brain function. In a clinical trial with volunteers who reported memory problems, results of PET scans using FDDNP correlated well with the volunteers' clinical diagnoses measured by performance on memory tests.
"Today, an estimated 4.5 million Americans have Alzheimer's disease, and that number could triple by 2050 as the population ages. We urgently need techniques to see brain changes in the earliest stages of cognitive decline so that we can identify people at risk and test drugs to stop or slow the progression of Alzheimer's," says NIA Director Richard J. Hodes, M.D.
In this study, Gary Small, M.D., of UCLA, led a research team that compared PET scans using FDDNP, PET scans using another molecule (FDG) to measure brain activity, and magnetic resonance imaging (MRI), which can show areas losing brain tissue in Alzheimer's disease. Of 83 people who volunteered for the trial, researchers classified 25 as having Alzheimer's, 28 as having mild cognitive impairment, and 30 as healthy. The FDDNP PET scans were more accurate than FDG PET scans or MRI at detecting differences among the groups of volunteers, the study found. Two years later, follow-up testing on a subset of the volunteers showed that FDDNP PET scans continued to correlate well with their clinical symptoms and diagnoses.
"The hope is that better imaging techniques and markers will allow us to conduct clinical trials with fewer volunteers and in less time," says Susan Molchan, M.D., program officer in the NIA Neuroscience and Neuropsychology of Aging Program. "The ability to image brain changes may allow us to see how drugs affect the accumulation of proteins in the brain that cause Alzheimer's plaques and tangles, possibly preventing or delaying the progression of Alzheimer's."
In a separate but related project, NIA also leads the Alzheimer's Disease Neuroimaging Initiative (ADNI), a federal government and private sector partnership that seeks to discover imaging techniques and other biomarkers that, over time, can measure biological changes in the progression from mild cognitive impairment to Alzheimer's disease. One component of the initiative will compare PET scans using another compound that binds to Alzheimer's disease plaques, Pittsburgh Compound B, with other tests.
ADNI began last year and continues to recruit new participants. People can learn more about joining ADNI and obtain a list of U.S. and Canadian trial sites by contacting NIA's Alzheimer's Disease Education and Referral (ADEAR) Center at 1-800-438-4380 or by visiting www.nia.nih.gov/alzheimers.
Beyond public support from NIA, the National Institute of Mental Health and the National Center for Research Resources, components of NIH at the U.S. Department of Health and Human Services, and the U.S. Department of Energy, the research by Small and colleagues was supported by a number of foundations. UCLA owns a patent for FDDNP, and Small and colleagues have a financial interest in the molecule.
NIA leads the federal effort supporting and conducting research on aging and the medical, social and behavioral issues of older people, including Alzheimer's disease and age-related cognitive decline. For information on dementia and aging, including information for patients and caregivers, please visit the ADEAR Center web site, www.nia.nih.gov/alzheimers, or call 1-800-438-4380. For more general information on research and aging, go to www.nia.nih.gov.
NIH--the nation's medical research agency--includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Reference: G.W. Small et al. PET of Brain Amyloid and Tau in Mild Cognitive Impairment. The New England Journal of Medicine. Vol:355;25. pp:2652-63. Dec. 21, 2006.
New England Journal of Medicine