Vitamins, Drugs Of Limited Benefit for Mild Cognitive Impairment

April 19, 2005

April 19, 2005

A rigorous new study has concluded that a popular vitamin supplement and a prescription medicine for Alzheimer’s did little if any to delay progression from mild cognitive impairment to Alzheimer’s disease. Mild cognitive impairment, or MCI, is a somewhat serious form of memory loss or loss of other cognitive faculties that strikes some elderly men and women. It is more severe than common age-related forgetfulness, and less severe than Alzheimer’s disease. Mild cognitive impairment, in some people, progresses to Alzheimer’s disease in anywhere from one to ten or more years.

Vitamin E, a popular nutritional supplement commonly taken to stem the decline of Alzheimer’s disease, appeared to have no effect in delaying progression. But it did have a mild effect at slowing the decline of certain cognitive abilities other than memory (e.g., language). Aricept, a popular drug used to treat early Alzheimer’s, however, showed more promise. It delayed somewhat the progression to Alzheimer’s during the first year of treatment, but at later times did not delay progression in those with MCI.

Mild cognitive impairment is a more severe form of memory loss than the ordinary forgetfulness that strikes many as they age. MCI can affect memory, language, attention, critical thinking, reading and writing, and other skills. However, symptoms of MCI are nowhere near as severe as the profound memory impairment, loss of reasoning skills, and personality changes that accompany Alzheimer’s disease. For example, people with MCI typically go about their daily lives, with much of their judgment, perception, and reasoning skill intact.

Some but not all people with MCI go on to develop Alzheimer’s disease. In some studies, up to 16 percent of people with MCI, particularly those whose main symptom is memory loss, go on to develop Alzheimer’s disease each year. In the current study, researchers studied vitamin E and Aricept (generic name donepezil) because both have shown some benefit for people with Alzheimer’s disease in earlier research. Both are also considered generally safe, although some recent research has called into question the safety of high-dose vitamin E.

Investigators were hopeful that one or both might help stem memory loss at an earlier step in the process and stem the progression from MCI to full-blown Alzheimer’s disease.

Vitamin E, Aricept

The study involved 769 older men and women at various medical centers across the United States and Canada. They ranged in age from 55 to 90 years. All had a type of MCI that affected primarily their memories a form of the condition that is especially likely to progress to Alzheimer’s disease.

One third of the study participants with MCI were given Aricept, a drug that has been shown to slow the progression of memory loss in those with mild to moderate Alzheimer’s. Another third were given high doses of vitamin E (2,000 IU a day), a popular cell-protecting antioxidant that some research suggests may protect brain cells against damage from an excess of naturally formed compounds called free radicals. The remaining third received a look-alike dummy pill (placebo). All the study participants also received a general multivitamin. Each group was given memory tests and other exams at the start of the study and then every six months. They continued to take the pills for three years, but nobody knew who was getting which type of pill.

At the end of three years, those who had been receiving vitamin E fared no better than those who had been getting a placebo. About 16 percent in either group went on to develop Alzheimer’s disease. The results were disappointing, because one earlier study had suggested that the vitamin might help to slow memory decline in those with moderately severe Alzheimer’s disease.

Aricept, on the other hand, showed some promise, although benefits were modest. The drug appeared to slow the progression to Alzheimer’s during the first year of the study. Unfortunately, any benefits from the drug wore off by year three, so that there were no differences in the rate of progression to Alzheimer’s between the Aricept and placebo groups. Researchers estimate that Aricept slowed progression from MCI to Alzheimer’s, on average, by about six months. The drug, however, did not permanently prevent the worsening of memory.

Still, doctors are hopeful that Aricept or related drugs such as Exelon (rivastigmine) or Razadyne (galantamine), as well as new drugs under development, may offer some benefits for MCI. While the results in the current study were modest, they are among the first to suggest that very early treatment may help some people in the earliest stages of mental decline. Further research and follow-up is called for.

The findings were published in The New England Journal of Medicine, a highly respected publication for doctors.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Deborah Blacker, MD, ScD, “Mild Cognitive Impairment: “No Benefit from Vitamin E, Little from Donepezil” (editorial). New England Journal of Medicine, 10:1056, April 14, 2005.

Ronald C. Petersen, PhD, MD, Ronald G. Thomas, PhD, Michael Grundman, MD, MPH, et al: “Vitamin E and Donepezil  for the Treatment of Mild Cognitive Impairment.” New England Journal of Medicine, 10:1056, April 14, 2005.


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