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People with mild cognitive impairment (MCI) taking the drug donepezil
were at reduced risk of progressing to Alzheimer's disease (AD) for
the first 18 months of a 3-year study when compared with their counterparts
on placebo, according to a presentation of preliminary data from
a recently completed clinical trial supported by the National Institute
on Aging (NIA), part of the National Institutes of Health. The reduced
risk of progressing from MCI to a diagnosis of AD among participants
on donepezil disappeared after 18 months, and by the end of the study,
the probability of progressing to AD was the same in the two groups.
The study compared donepezil, vitamin E, or placebo in participants with MCI
to see whether the drugs might delay or prevent progression to AD. Over the
course of the study, among people who did progress to AD, the MCI participants
on donepezil averaged 661 days until a diagnosis of AD, a second group on vitamin
E averaged 540 days from MCI to AD, and those on placebo averaged 484 days
to AD. The study investigators reported a statistically significant effect
when donepezil was compared to placebo, but said there was no apparent benefit
from vitamin E.
The study is part of the Alzheimer's Disease Cooperative Study clinical trials
consortium supported by NIA. Ronald Petersen, M.D., Ph.D., of the Mayo Clinic,
Rochester MN, was principal investigator for this trial. Leon Thal, M.D., University
of California at San Diego, heads the Alzheimer's Disease Cooperative Study.
The NIA and the scientists conducting the study emphasized that further analyses
will be needed to assess the practical, clinical implications of the new data;
the study is very complex, and the effects appear time limited. “We will
subject the data to considerable scrutiny over the next few months for additional
information on whether and, if so, when the drug could benefit people with
MCI.” said Neil Buckholtz, Ph.D., Chief of the NIA’s Dementias
of Aging Branch. “Today's presentation of a possible but limited effect
of donepezil is encouraging. But we are hoping that further clinical studies
in MCI patients will result in more significant progress in delaying a diagnosis
of Alzheimer's disease.”
The preliminary data from the Memory Impairment Study were presented at the
Alzheimer Association’s 9th International Conference on Research on AD
and Related Disorders (ICAD) in Philadelphia on July 18, 2004. Besides primary
support from the NIA, additional funding for the study was provided by Pfizer,
Inc., and Eisai Inc. Pfizer and Eisai additionally contributed the donepezil
study medication, and vitamin E was given by DSM Nutritional Products, Inc.
People with this form of MCI have notable memory loss and are at higher risk
of developing AD than those of similar age and health in the general population.
During the study, patients with MCI were given donepezil, vitamin E, or a placebo.
Donepezil was selected because of its current approval as a drug for treating
patients already diagnosed with AD. The antioxidant vitamin E has been linked
in animal research to a reduction in cognitive decline and in some population
studies to reduced risk of AD.
In addition to being tested for AD, the participants were assessed in specific
areas of cognitive function, including orientation, language, and attention,
and in everyday function, such as activities of daily living. These secondary
analyses suggest that decline among the group on donepezil occurred at a slower
rate on tests of global cognition, memory, and language than the other participants
during the first half of the study but progressed at the same rate thereafter.
“Certainly, we need to continue our analyses,” said the study’s
principal investigator Petersen. “But these are the first reported data
to show some kind of positive treatment effect on progression from MCI to AD,
suggesting that it may be possible to design better trials to intervene at
an earlier stage in the disease process and slow the progression to AD.”
The Memory Impairment Study was conducted nationwide at 69 sites. It involved
769 participants with MCI, who were followed for 3 years and tested for AD
at 6-month intervals during their 36 months in the study. The average age of
the participants was 73.
The NIA is currently funding 7 prevention trials and 19 treatment trials for
AD. Many of these trials are continuing to enroll participants, including,
for example, trials testing anti-inflammatory drugs, a statin drug, and B vitamins
and folate. For more information on participation in an AD clinical trial,
visit www.clinicaltrials.gov (search for Alzheimer’s disease trials),
or visit the Alzheimer’s Disease Education and Referral (ADEAR) Center
website at www.alzheimers.org ADEAR.
ADEAR can also be contacted toll free at 1-800-438-4380.
The ADEAR Center is sponsored by the NIA to provide information to the public
and health professionals about AD and age-related cognitive change and can
be contacted at the website and phone number above for a variety of publications
and fact sheets, as well as information on clinical trials.
Information on clinical trials and AD can also be obtained from the Alzheimer’s
Association, the private national advocacy organization for families and patients
with AD. The Association’s website is www.alz.org.
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