For first time, a current Alzheimer drug may delay transition from MCI to Alzheimer's
PHILADELPHIA, Sunday, July 18 – Individuals with mild cognitive impairment (MCI) who took the Alzheimer drug donepezil had a reduced risk of progressing to Alzheimer's disease compared to those who took placebo, according to preliminary data reported today at the 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer's Association.
The risk reduction appeared to be temporary, lasting for only the first 18 months of a three-year trial. When individuals in the study did progress to Alzheimer's, those taking donepezil developed the disorder an average of six months later than those taking the placebo.
"This is the first study to demonstrate a positive treatment effect on progression to Alzheimer's disease from MCI," said Ronald Petersen, M.D., Ph.D., a principal investigator in the study, which was funded by the National Institute on Aging (NIA). "It looks like the drug had a modest, time-limited effect. Nonetheless, we are optimistic because we have begun to make progress toward delaying the development of Alzheimer's."
MCI is often but not always a transitional state between normal aging and Alzheimer's disease. A person with MCI experiences memory problems greater than normally expected with aging, but does not show other symptoms of Alzheimer's, such as difficulties in performing activities of daily living.
Two other studies reported at ICAD found that factors including age, level of education, rural residence in youth, history of head injury, and presence of the e4 allele of the APOE gene were associated with higher frequency of MCI, but not race or ethnicity as had been previously reported.
"These encouraging studies show that we need more research to help us answer the question of which cases of MCI are most likely to progress to Alzheimer's, and whether it is justified and effective to begin treating those people with current or future therapies," said Claudia Kawas, M.D., a member of the Alzheimer's Association's Medical and Scientific Advisory Council. "It is vitally important to be able to intervene in Alzheimer's early to delay or prevent the onset of symptoms.
Alzheimer Therapy May Benefit People With MCI Among the most anticipated studies at the ICAD were the preliminary findings from a clinical trial of donepezil (Aricept, Eisai/Pfizer) and vitamin E in people with MCI. Ronald Petersen, M.D., Ph.D., of the Mayo Clinic in Rochester, Minnesota, and Leon Thal, M.D., University of California, San Diego, led the multicenter trial, which was sponsored by the National Institute on Aging (NIA) as part of its Alzheimer's Disease Cooperative Study clinical trials consortium. Pfizer, Eisai and DSM Nutritional Products, Inc. provided additional support. The trial was a randomized, double-blind, placebo-controlled study of 769 people with MCI who had been assigned to treatment arms with either 10 mg/day donepezil, 2000 IU/day vitamin E or placebo.
Over the course of the 3-year study, the MCI subjects progressed to Alzheimer's disease at a rate of 13 percent per year, compared to about 1-2 percent per year in people of similar age without MCI. The donepezil treated group appeared to develop Alzheimer's disease more slowly for the first 18 months of the trial, but then was not significantly different from the untreated placebo group for the remainder of the study. There was no apparent benefit derived from the treatment with vitamin E.
The researchers cautioned that much further analysis is needed before clinical recommendations can be made about whether the drug should be taken at this early stage of cognitive impairment, and at what point it might be most effective.
"This study gives us hope for the effectiveness of early intervention and raises the urgency for developing accurate ways to identify Alzheimer's earlier in the process and treat the disease even more effectively," Kawas said.
Age and Education Associated with MCI, Not Race Many researchers believe that tests used to detect memory impairments are not as accurate among ethnic minorities and elders with few years of education. As a result, African American and Hispanic elders are more likely to be misdiagnosed with cognitive impairment. This is potentially a problem for research studies of MCI among ethnically diverse elders, and also for studies to test the efficacy of treatments to prevent or slow progression of Alzheimer's.
Researchers led by Jennifer Manly, Ph.D., of Columbia University Medical Center, attempted to address this problem by establishing appropriate expectations for cognitive test performance based on ethnic group, educational level, and age.
They studied 1,654 nondemented elderly in Northern Manhattan in a neighborhood that is roughly 50 percent Hispanic, 30 percent African American, and 20 percent White. Once given thorough evaluation, participants were classified as having amnestic MCI (which involves isolated impairment in memory) as well as other subtypes of MCI depending on whether executive function, language, or visuospatial skill were affected in isolation or with memory.
The frequency of amnestic MCI was 3.7 percent. Other subtypes of MCI ranged in frequency from 2.7 to 10.0 percent. MCI was more frequent among elders age 75 years and older compared to those age 65 – 75 years. Individuals with fewer than nine years of school were also more likely to meet MCI criteria, even when the tests accounted for educational level. IN addition, cardiovascular risk factors such as hypertension, diabetes, and heart disease were more common among those with MCI.
"When proper normative values were used, only age and education were associated with higher frequency of MCI, not race or ethnicity," Manly said.
More Cognitive Impairment Each Year Than Dementia or Alzheimer's Another term for the group of people in the category between normal aging and dementia is Cognitive Impairment No Dementia (CIND). Frederick Unverzagt, Ph.D., of Indiana University School of Medicine, and colleagues investigated the number of new cases of, and risk factors for, CIND in African Americans age 65 and older in Indianapolis. 2,212 participants started in the study. 1,668 completed a 2-year re-screening; 1,255 participants completed a 5-year follow-up.
The researchers found there were more new cases of CIND each year than dementia or Alzheimer's. The annual incidence of CIND was 4.8 percent, compared to 3.2 percent for dementia and 2.5 percent for Alzheimer's. Risk of developing CIND was increased by rural residence in youth, history of head injury, and presence of the e4 allele of the APOE gene. Head injury and APOE-e4 have been identified as risk factors for Alzheimer's, as well.
"This group is of interest because people in it develop dementia at a much higher rate than normal elderly," Unverzagt said. "We found that some but not all persons with CIND are in the earliest stages of Alzheimer's. We need to identify the factors associated with progression from CIND to dementia and Alzheimer's in large community populations."
The 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer's Association, is the largest gathering of Alzheimer researchers in history. More than 4,500 scientists from around the world will present and discuss the findings of 2,000 studies showcasing the newest treatment advances in Alzheimer's disease and steps toward prevention. ICAD will be held July 17-22, 2004, at the Pennsylvania Convention Center in Philadelphia, Pennsylvania.
The Alzheimer's Association is the world leader in Alzheimer research and support. Having awarded more than $165 million to nearly 1,400 projects, the Alzheimer's Association is the largest private funder of Alzheimer research. To sustain the rapid progress, the Association calls for $1 billion in annual federal funding for Alzheimer research. For more information about Alzheimer's disease, visit http://www.alz.org or call 800-272-3900.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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