Could Shorten Testing Time to One or Two Years; 'Save A Generation'
PHOENIX, March 13 /PRNewswire/ -- A study published today in the Proceedings of the National Academy of Sciences may hold the answer to a vexing problem facing medical scientists involved in Alzheimer's disease research -- how to test Alzheimer's prevention drugs in a relatively short time period.
"In the last few years, researchers have made remarkable scientific progress in the effort to understand, treat, and even prevent Alzheimer's disease," said the study's principal investigator, Eric Reiman, MD, of Good
Samaritan Regional Medical Center in Phoenix, Ariz. "A strategy is needed to test the potential of treatments to prevent this disorder without having to wait many years to determine whether or when research subjects develop
symptoms."
The study utilized the capabilities of Positron Emission Tomography (PET), which is an imaging technique that provides information about the inner workings of the brain.
The study capitalized on studies of persons at genetic risk for Alzheimer's disease. The APOE-4 gene is found in about one-fourth of the population and appears to account for about half of those who develop Alzheimer's symptoms. Reiman and his team found that cognitively normal, late
middle-aged persons with a copy of the APOE-4 gene had distinctive declines in PET measurements of sugar utilization, a measure of brain activity.
From these findings, they determined that PET could be used to efficiently to test the potential of treatments to prevent Alzheimer's disease in as few as 100 to 200 cognitively normal APOE-4 carriers in just one or two years. In contrast, a study that relied on clinical evidence of Alzheimer's disease would likely require thousands of research subjects and take many years,
particularly if the treatment is started in the research subjects' 50s or 60s.
"When one considers the toll that Alzheimer's disease takes on affected persons and their families, it is critically important to identify treatments to prevent the disorder without losing a generation along the way," said
Reiman.
Alzheimer's disease is the most common form of cognitive impairment in older persons, afflicting 10 percent of those over the age of 65 and almost half of those over 85. Due to an aging population and the prevalence of Alzheimer's, the incidence of the disease is projected to quadruple in the next 50 years. "Without an effective way to treat and prevent this disorder,
Alzheimer's disease is projected to become a catastrophic public health problem," said Reiman.
Studies performed by Reiman and his colleagues have shown how PET could be used to track the progression of Alzheimer's disease prior to the onset of memory and thinking problems in carriers of the APOE-4 gene. In a study previously published in the New England Journal of Medicine, the investigators found abnormally low brain activity in cognitively normal, late middle-aged
persons with the APOE-4 gene at the time of their baseline PET scans. In the present study, they found that brain activity continues to decline over two years in persons who are APOE-4 carriers in the absence of memory or thinking
problems. This decline is greater than that found in persons who are not APOE-4 gene carriers. (Similar findings have been reported by researchers at UCLA in a complementary study of older APOE-4 carriers with memory concerns.)
Based on the rate of this decline, they determined the number of APOE-4 carriers that would be required to test treatments to slow down the decline in PET measurements in just one or two years. If, as studies suggest, the
decline in brain activity is related to the development of Alzheimer's disease, Reiman proposes that PET could be used in the APOE-4 gene carriers to efficiently test the potential of treatments to prevent this devastating
disorder.
Researchers have already raised the possibility that several currently available treatments might decrease the risk and delay the onset of memory and thinking problems caused by Alzheimer's disease. Potential prevention
therapies that are currently available include anti-oxidants like vitamin E, anti-inflammatory medications, hormone replacement therapy, and a class of medications known as cholinesterase inhibitors, which is already approved for the treatment of affected patients. Even more promising treatments, including an innovative immunization therapy and a class of medications known as "plaque busters," are now being developed, and some of these have begun to be tested for their safety.
According to Reiman, even modestly successful treatments could have an enormous public health benefit. A treatment that delayed the onset of the disorder by five years would cut the number of new cases in half. By the year 2050, such a treatment could reduce the projected number of affected persons from 16 million to 9 million cases and reduce the projected cost of the disorder from 750 to 425 billion dollars per year.
Eric Reiman, MD, who is the study's principal investigator, is a full-time faculty member in the Department of Psychiatry at Good Samaritan. He is the
Scientific Director of the Good Samaritan PET Center, has an appointment at the University of Arizona College of Medicine, and is Scientific Director of the state-supported, multi-institutional Arizona Alzheimer's Research Center.*
Richard Caselli, MD, is the study's co-principal investigator. He is Chairman of the Neurology Department at Mayo Clinic Scottsdale. Other investigators of
the study are Kewei Chen, Ph.D. of the Good Samaritan PET Center and Gene Alexander of Arizona State University. The study was supported by grants from the National Institutes of Health, the Banner Health Foundation of Arizona, Mayo Clinic Foundation, and the State of Arizona.
* The Arizona Alzheimer's Research Center is a research consortium that capitalizes on the state's resources in brain imaging, computer science and the basic and behavioral neurosciences at seven of the state's biomedical
research institutions. These institutions include Arizona State University, Barrow Neurological Institute, Good Samaritan Regional Medical Center, Harrington Arthritis Research Center, Mayo Clinic Scottsdale, Sun Health
Research Institute, and the University of Arizona.
For additional information, please contact the Good Samaritan Regional Medical Center's Public Relations office at (602) 239-4411 or visit the Web site at bannerhealthaz.com. |
