Donepezil May Have Short-Term Benefit for Mild Cognitive Impairment
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 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. 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.
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.
NIACIN MAY PROTECT AGAINST ALZHEIMER DISEASE: July 16, 2004
The study in the Journal of Neurology, Neurosurgery, and Psychiatry points out that severe niacin deficiency is known to cause dementia. However, the researchers note that it is unclear if more subtle variations in niacin intake influence the risk of mental deterioration.
"There have been no epidemiologic studies to look at the association between dietary niacin and Alzheimer's disease or cognitive decline," lead author Dr. Martha C. Morris, from the Rush Institute for Healthy Aging in Chicago, told Reuters Health. Moreover, "animal studies and other studies have really focused on the effects of very high therapeutic dose levels of niacin," not amounts found in a standard diet. To investigate, the researchers asked several thousand elderly people living in a Chicago community about the types and amounts of food they ate and tested their mental abilities.
The study focused on 815 randomly selected subjects who were free from Alzheimer's disease at the start of the study. After an average of nearly four years, 131 of the participants were diagnosed with Alzheimer's disease. A high level of total niacin intake seemed to protect against both Alzheimer's disease and cognitive decline. The association was stronger for niacin intake from foods than for niacin taken in vitamin supplements.
"We were surprised to see a fairly strong association between niacin intake from foods and Alzheimer's disease," Morris said. Compared with the lowest intake, the highest intake "was linked to an 80 percent reduction in risk." In the overall study population, high niacin intake was also linked to a reduced risk of cognitive decline. Although the finding are provocative, Morris concluded, they will require verification before any changes to current dietary guidelines can be recommended.
SOURCE: the Journal of Neurology, Neurosurgery, and Psychiatry; August 2004.
NIA News: AD Research Update
Diabetes Linked to Increased Risk of Alzheimer's in Long-Term Study May 17, 2004
Excerpted from http://www.alzheimers.org/nianews/nianews65.html
Diabetes mellitus was linked to a 65 percent increased risk of developing Alzheimer's disease (AD), appearing to affect some aspects of cognitive function differently than others in a new study supported by the National Institute on Aging (NIA) at the National Institutes of Health. The findings, from the Rush Alzheimer's Disease Center's Religious Orders Study, add to a developing body of research examining a possible link between diabetes and cognitive decline. The results reported today are among the first to examine how certain cognitive "systems" - memory for words and events, the speed of processing information, and the ability to recognize spatial patterns -- may be affected selectively in people with diabetes.
The research, by Zoe Arvanitakis, M.D., David Bennett, M.D., and colleagues at the Rush University Medical Center in Chicago, IL, appears in the May 2004 issue of the Archives of Neurology. The investigators are part of the institution's Rush Alzheimer's Disease Center, headed by Dr. Bennett. The AD Center is one of 30 across the U.S. supported by the NIA to study and care for Alzheimer's patients.
"The research on a possible link between diabetes and increased risk of AD is intriguing, and this study gives us important additional insights," says Neil Buckholtz, Ph.D., head of the Dementias of Aging Branch in the NIA's neurosciences program. "Further research, some currently underway, will tell us whether therapies for diabetes may in fact play a role in lowering risk of AD or cognitive decline."
Some 824 Catholic nuns, priests, and brothers participating in the Religious Orders Study were followed for an average of 5.5 years. They received detailed clinical evaluations annually, including neuropsychological testing of five cognitive "systems" commonly affected by aging, AD, and other dementias - episodic memory (memory of specific life events), semantic memory (general knowledge), working memory (ability to hold and mentally rearrange information), perceptual speed (the speed with which simple perceptual comparisons can be made, such as whether two strings of numbers are the same or different), and visuospatial ability (the ability to recognize spatial patterns).
Over the study period, 151 of the participants had a clinical diagnosis of AD, including 31 who had diabetes. The researchers found a 65 percent increase in the risk of developing AD among those with diabetes compared with people who did not have diabetes.
In measures of cognitive function, only in the area of perceptual speed was there an association with an increased rate of decline over time, by about 44%, when comparing the diabetes and non-diabetes groups. Since stroke-related changes in the brain were found in a previous study to be tied to a decline in perceptual speed, the researchers could not say whether the link between cognitive decline and diabetes appeared because of the changes in the brain associated with Alzheimer's disease or those of some other common age-related condition like stroke or other vascular complications. Studies looking at pathological or brain imaging data would be needed to address these possibilities.
In other areas of cognition, the rate of change over the time period of the study was no different in the two groups. However, at the start of the study, the baseline cognitive function scores of people with diabetes were lower than those of people without diabetes.
"We found that diabetes was related to decline in some cognitive systems but not in others," says Dr. Arvanitakis of Rush, the lead author of the report. "Since all participants have agreed to brain donation at their deaths, we will have the opportunity to examine the pathologic basis of the association of diabetes to cognitive decline." The Rush researchers also expressed their indebtedness to the more than 1,000 nuns, priests, and brothers from across the U.S. participating in the Religious Orders Study.
The NIA is the lead Federal agency conducting and supporting research on Alzheimer's disease and age-related cognitive change. For more information, readers and viewers can visit the NIA's Alzheimer's Disease Education and Referral (ADEAR) Center at http://www.alzheimers.org or call toll-free 1-800-438-4380. Information on aging generally may be viewed at the NIA's general website at http://www.nia.nih.gov or by calling the NIA Information Center at 1-800-222-2225.
For information on diabetes, see the website of the National Institute on Diabetes, Digestive, and Kidney Diseases (NIDDK), at http://www.niddk.nih.gov, or call the National Diabetes Information Clearinghouse, a service of the NIDDK, at 1-800-860-8747.
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