The five-year grant, one of the largest ever awarded by the NIA, doubles support for the Alzheimer’s Disease Cooperative Study (ADCS), formed in 1991 as a cooperative agreement between the NIA and the University of California, San Diego (UCSD), and directed by Leon Thal, M.D., chair of the Department of Neurosciences, UCSD School of Medicine. The previous 5-year grant totaled $27 million.
Composed of Alzheimer’s researchers at 83 sites in the United States and Canada, the ADCS conducts coordinated clinical trials of new approaches to treating and preventing Alzheimer’s disease. In the past 10 years, nearly 2,500 volunteers have participated in 13 research protocols, with some positive results now in practice. Five new studies are planned for the next five years.
"In the next 10 years or less, we should be able to delay the onset of Alzheimer’s disease," said Thal, who also directs UCSD’s Alzheimer’s Disease Research Center. "In the past 10 years, thanks to support from the NIA, we have made significant progress in the fight against Alzheimer’s disease. We’ve established a group of nationally and internationally recognized Alzheimer’s researchers. With multiple sites working together, the ADCS is large enough to generate significant results in a reasonable period of time, giving us better data from which to draw conclusions."
"NIA is excited about this next round of the ADCS," said Neil Buckholtz, Ph.D., who directs the project and dementia research for the NIA. "We have new assessment and diagnostic tools and a better sense than ever of which drugs might have a chance of working. I am expecting that we will make some inroads against the disease, with the ADCS playing a critical role in facilitating the testing of possible new treatments."
A progressive disease characterized by death of nerve cells in several areas of the brain, resulting in loss of memory, Alzheimer’s disease is the most common type of dementia. Symptoms include gradual memory loss, decline in the ability to perform routine tasks, disorientation, difficulty in learning, loss of language skills, impairment of judgment and planning and personality changes. Eventually patients become totally incapable of caring for themselves. The disease is incurable and ultimately fatal.
"Researchers are fairly close to identifying the proximate cause of the disease and the many places where we can intervene," said Thal. "One current hypothesis is that Alzheimer’s disease is related to the accumulation in the brain of an abnormal, toxic protein called beta amyloid. Unless this hypothesis is wrong, one or more of the research efforts to prevent beta amyloid deposits will turn out to be successful."
While researchers are optimistic about treatment and prevention related to beta amyloid, "it’s important that we don’t concentrate only on a single area," Thal said. "It’s vital that the ADCS continue to pursue other potential treatments for Alzheimer’s disease."
ADCS Findings
The ADCS has completed two trials with major public health impact. In one, researchers demonstrated that vitamin E slowed the progression of Alzheimer’s disease, although it did not affect cognition. A recent survey of neurologists, psychiatrists, family practitioners and internists, has shown that the ADCS findings led to vitamin E being the most widely prescribed medication for Alzheimer’s patients in the U.S.
The second ADCS study with implications Alzheimer’s treatment involved estrogen replacement therapy. Despite widespread belief to the contrary, researchers found that estrogen does not slow the rate of decline in certain women with Alzheimer’s disease.
Other findings and results by ADCS researchers include:
· Designation of mild cognitive impairment (MCI) as a treatable entity and development of a clinical trial to delay conversion from MCI to Alzheimer’s disease;
· Design of new instruments to aid in the assessment of cognitive decline;
· Development of Spanish-language assessment tools.
Additional clinical trials in the past 10 years have investigated drugs to treat agitation, reduce inflammation, improve sleep, and stimulate regrowth of damaged nerve cells. Some of these trials are still in progress while others are at the stage of data analysis.
New Studies Planned
During the next five years of ADCS trials, researchers will continue a study begun in 1997 with more than 700 patients who have mild cognitive impairment. They hope to learn if conversion to Alzheimer’s disease can be prevented with vitamin E or donepezil, a drug designed to increase acetylcholine, a brain chemical associated with memory. The principal investigators for this trial are Ronald Petersen, M.D., Ph.D, professor of neurology, Mayo Clinic and Michael Grundman, M.D., MPH , associate professor of neurosciences, UCSD.
Thal said he is particularly excited about an upcoming test of a cholesterol lowering agent called a statin, to determine if it also slows the progression of Alzheimer’s disease. There is growing evidence from clinical epidemiological and laboratory studies that cholesterol may play a role in the origin and development of Alzheimer’s disease. The principal investigator for this trial is Mary Sano, Ph.D., associate professor of clinical neuropsychology, Columbia University.
The ADCS will continue its role in the development of assessment measures that gauge changes in cognition, activities of daily living, and quality of life, among other factors. Researchers will design sensitive, more effective methods for evaluating change and allowing collection of data in the home, which will make it easier for the patient and reduce the cost of very expensive prevention trials. Also planned for the next five years are studies of:
· High doses of vitamin combinations (folate/B6/B12) that have been shown to reduce homocysteine levels, a possible risk factor for Alzheimer’s disease;
· A potent, naturally occurring antioxidant called indole-3-propionic acid (IPA); and
· Valproate, an antipsychotic drug, to delay the emergence of agitation and psychosis which often co-occur with Alzheimer’s disease and have a particularly high persistence rate in Alzheimer’s patients.
Contact for National Institute on Aging:
Vicky Cahan
301-496-1752
cahanv@nia.nih.gov
Link to National Institute on Aging’s Alzheimer’s Disease Education and Referral (ADEAR) Center: http://www.alzheimers.org
Link to Alzheimer’s Disease Cooperative Study: http://antimony.ucsd.edu
Link to UCSD Alzheimer’s Disease Research Center: http://adrc.ucsd.edu
Link to background information about Leon Thal, M.D.:
http://medicine.ucsd.edu/neurosci/the-faculty/thal.html
http://health.ucsd.edu/ucsd_md/lthal.htm