Donepezil May Have Short-Term Benefit for Mild Cognitive Impairment|
More Analyses Needed to Assess Clinical Implications of New Data
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 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