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OHSU Alzheimer's Center Part of NIH Neuroimaging Effort

   Portland, Ore.

National initiative calls for comparing techniques for measuring cognitive decline.

Oregon Health & Science University is participating in a comprehensive national study that will compare neurological imaging data to monitor progression of cognitive decline, including that associated with Alzheimer's disease.

The Layton Aging & Alzheimer's Disease Center in the OHSU School of Medicine's Department of Neurology is one of 50 sites across the country taking part in the five-year, $60 million Alzheimer's Disease Neuroimaging Initiative - ADNI - funded primarily by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and the Food and Drug Administration.

"OHSU is very pleased to be one of the sites for this major national initiative," said Jeffrey Kaye, M.D., professor of neurology and director of the Layton center.

Scientists will compare information from magnetic resonance imaging (MRI) and positron emission tomography (PET) with known biological indicators of dementia, and clinical and neuropsychological assessments. Their goal is to find correlations that will help them track the advancement of memory loss from its inception and, ultimately, allow researchers and clinicians to develop and monitor new treatments.

"The need is for a uniform dataset that will guide treatment around the country and the world such that one can reliably say that if this drug is working, these biomarkers should change by a predictable amount," Kaye said. "Currently, these important benchmarks are not uniform."

The National Institutes of Health calls the initiative the most comprehensive effort to date to find neuroimaging and other biological markers for the cognitive changes associated with mild cognitive impairment and Alzheimer's disease.

Kaye, who serves on ADNI's national steering committee and who helped design the protocol for the upcoming clinical trials, said the Layton Center has been well poised as a site for a study of this magnitude.

"Our site, in particular, is unique because we are one of the few sites that will be involved in not just the neuroimaging portion of the initiative, but also in obtaining the biochemical measures in the blood and spinal fluid," he said.

Indeed, OHSU is one of only a handful of institutions around the country that specializes in longitudinal studies on biological markers for dementia found in blood, cerebrospinal fluid and urine. It also possesses a solid network of study volunteers, and its team of neurologists specializing in cognitive assessment is top tier.

"We have an excellent relationship with the community and the volunteers that are necessary to be in this project over many years," Kaye said. "And we have a great deal of expertise in performing the imaging techniques that are planned for this project."

ADNI investigators will begin recruiting 800 adults ages 55 to 90 for the study in April 2005. About 200 cognitively normal older individuals will be tracked for three years, 400 people with mild cognitive impairment will be monitored for two years, and 200 people with early Alzheimer's disease will be followed for two years.

Kaye said he hopes to recruit about 50 volunteers for the Layton center's portion of the study. "Participants will need to be screened, they can't have certain medical conditions and, obviously, they have to sign a consent to participate."

Layton researchers will study "how the brain loses volume over time," Kaye said. "We also will be periodically taking cerebrospinal fluid and blood samples to look at things such as the amyloid proteins we think accumulate as people develop Alzheimer's disease." Spinal fluid is important because it "bathes the brain and has many of the chemicals we think might be related to why the brain starts to atrophy or degenerate."

Another accumulating protein associated with Alzheimer's, tau, will be studied, along with markers of oxidative stress, such as oxysterols and isoprostanes. Other biomarkers to be examined are C-reactive proteins and alpha-anti-chymotrypsin, which may be indicators of dementia-related inflammation, and genes associated with increased risk of Alzheimer's.

Neuropsychological assessments will be important in tying the clinical status of volunteers to the biomarkers, Kaye said.

OHSU has long tracked changes in the brain associated with Alzheimer's diseases using MRI. Among the Layton Center Neuroimaging Lab's many ongoing projects are the Oregon Brain Aging Study, which examines the effects of aging on the brain of healthy individuals; the African American Dementia & Aging Project, which examines age-related memory loss among African Americans; and the Dementia Prevention Study, a research trial investigating standardized ginkgo biloba extract.

Earlier this year, Layton center scientists following 55 people during a 14-year period found that rates of total brain volume loss may help identify patients with mild cognitive impairment who are at high risk of developing dementia. The discovery, presented to the American Academy of Neurology in April, could help doctors plan early treatment strategies and prevention studies.

The next step in the study is to recruit clinical trial volunteers and roll out the technical protocol that will assure all MRI scanners around the country meet the same quality control standards.

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