The National Institute on Aging (NIA) is launching a nationwide treatment study targeting individuals with mild cognitive impairment (MCI), a condition characterized by a memory deficit, but not dementia. The start-up of the trial, announced at a news conference held in Washington, D.C., coincides with publication of a separate NIA-funded study in this month's issue of Archives of Neurology * confirming that MCI is different from both dementia and normal age-related changes in memory. Accurate and early evaluation and treatment of MCI individuals might prevent further cognitive decline, including development of Alzheimer's disease (AD).
The upcoming Memory Impairment Study is the first such AD prevention clinical trial carried out by NIH, and will be conducted at 65-80 medical research institutions located in the United States and Canada. This study will test the usefulness of two drugs to slow or stop the conversion from MCI to AD. The trial will evaluate placebo, vitamin E, and donepezil, an investigational agent approved by the Food and Drug Administration for another use. Vitamin E (a-tocopherol) is thought to have antioxidant properties, and was shown in a 1997 study to delay important dementia milestones, such as patients' institutionalization or progression to severe dementia, by about seven months.
Participants will be randomly assigned to one of the three groups. The study will be carried out in 720 people over a 3-year period within the NIA's consortium of AD clinical research centers, called the Alzheimer's Disease Cooperative Study (ADCS). The study will be directed by Dr. Ronald C. Petersen, Ph.D., M.D., of the Mayo Clinic in Rochester, Minnesota, and Dr. Michael Grundman, M.D., M.P.H., of the University of California at San Diego (UCSD). Dr. Leon Thal, M.D., of UCSD directs the ADCS.
"While cognitive testing may reveal people with MCI to have a significant memory problem, their other cognitive functions remain normal and are for the most part unaffected by MCI," said Dr. Thal. "Prior to today, most treatments tested for slowing memory decline have been evaluated in patients with well-defined AD. What we hope to accomplish in this trial is to test agents that delay or stop further memory deterioration or the onset of AD in persons with MCI. In order to do that, it is our hope that as many people as possible with specific memory impairments volunteer to participate in this study."
In a different study, Dr. Petersen and colleagues at the Mayo Clinic compared the cognitive testing results of three groups of people: people with MCI, patients with mild AD, and people with normal memory. On memory measures, people with MCI performed worse than those with normal memory and were much more similar to patients with AD. On other cognitive measures, the MCI individuals were equivalent to people with normal memory and better than the AD patients. Dr. Petersen's study appears in the March 1999 issue of Archives of Neurology .
Investigators have long been interested in MCI in part because a significant number of people over the age of 65 with the condition eventually develop AD—as many as 12-15 percent of them per year (or about 40 percent after 3 years). Only 1 percent per year (or 3 percent after 3 years) of healthy people over the age of 65 develop AD. While individuals who eventually develop dementia go through a phase of mild cognitive impairment, some individuals with MCI may never convert to the clinical stages of AD.
The Memory Impairment Study targets people between the ages of 55 and 90. Those interested in participating in the clinical trial should have a memory complaint, exhibit memory impairment in testing—but be able to perform everyday activities normally—and should not have a clinical diagnosis of Alzheimer's disease. Information on patient recruitment for the trial is available by calling 1-888-455-0655 and at http://www.memorystudy.org .
Normal memory loss generally associated with aging is characterized by misplacing an item, forgetting someone's name, or forgetting to pick up something at the store. Memory loss associated with MCI is more severe and involves continuing problems in delayed recall of information. Abnormal memory loss, associated with dementia, is characterized by even more severe problems, such as disorientation, an inability to recall very recent events, and general confusion. A number of other conditions, diseases, and medications can cause many of the symptoms associated with dementia, making correct clinical evaluation essential.
"Before now, evaluating people with MCI has been difficult because we haven't had a clear definition of the symptoms of the disease," says Dr. Marcelle Morrison-Bogorad, Ph.D., Associate Director of NIA for the Neuroscience and Neuropsychology of Aging Program where the bulk of the Federal Government's Alzheimer's disease research is coordinated. "Now we can use information from Dr. Petersen's study and related studies to identify people with MCI and to develop ways to prevent or delay the onset of AD in this high-risk population. To delay or prevent the slide from mild cognitive impairment to dementia, even in a fraction of people, would have profound effects socially, financially, and otherwise."
The Memory Impairment Study is sponsored by the Alzheimer's Disease Cooperative Study at the University of California, San Diego with grant funding from the National Institute on Aging and contributions from Pfizer Inc. and Eisai Inc. Additional support is from Roche Vitamins Inc.
* Ronald C. Petersen, Ph.D., M.D., Glenn E. Smith, Ph.D., Stephen C. Waring, D.V.M., Ph.D., Robert J. Ivnik, Ph.D., Eric G. Tangalos, M.D., Emre Kikmen, M.D. "Mild Cognitive Impairment: Clinical Characterization and Outcome". Archives of Neurology . March 1999, pp. 303-308.
The NIA, one of 25 Institutes and Centers at the National Institutes of Health, leads the Federal effort in studying Alzheimer's disease and supporting basic, clinical, epidemiological and social research on aging and on the special needs of older people.