In a study of people with mild cognitive impairment ( MCI ), those who took the drug Donepezil were at reduced risk of progressing to a diagnosis of Alzheimer's disease (AD) during the first year of the trial, but by the end of the 3-year study there was no benefit from the drug.
Vitamin E was also tested in the study and was found to have no effect at any time point in the study when compared with placebo.

Mild cognitive impairment is a transitional state that occurs between the cognitive changes of normal aging and the very early stage of Alzheimer's disease.
The amnestic subtype of mild cognitive impairment, the focus of this research, involves memory problems not severe enough to be classified as dementia.
Previous studies have shown that approximately eight in 10 people who meet criteria for amnestic mild cognitive impairment progress to AD within 6 years of diagnosis and that people with the APOE-e4 gene progress to Alzheimer's disease more rapidly.

In this trial, Donepezil and the antioxidant vitamin E were each compared to placebo to see whether either treatment might delay or prevent progression to Alzheimer's disease among people with mild cognitive impairment.

Participants were randomized to three groups, one taking 2000 IU daily of vitamin E, the second receiving 10 mg of Donepezil daily, and the third on placebo.
All participants also took daily multivitamins.
The average age of the participants at baseline was 73 years.

Among the 769 study participants enrolled at 69 sites in the U.S. and Canada, 212 developed possible or probable Alzheimer's disease within the 3-year study period.

The overall rate of progression from mild cognitive impairment to AD for all three treatment groups combined was 16 percent per year.

Donepezil reduced the risk of progression to a diagnosis of Alzheimer's disease by 58 percent one year into the study, 36 percent at 2 years, but there was no risk reduction at the end of the full 3 years of the study.

The researchers examined the effect of Donepezil and vitamin E on delaying diagnosis of Alzheimer’s disease among a subset of people with MCI with apolipoprotein E-4 ( APOE-e4 ), the only known genetic risk factor for late-onset AD.
While the overall rate of progression to Alzheimer's disease was greater in this group, use of Donepezil in the APOE-e4 subset was beneficial for up to 36 months in reducing the risk of an AD diagnosis.

The researchers did not recommend APOE-e4 genotyping for people with mild cognitive impairment, suggesting more research would be needed to understand the mechanism of action of the drug and other factors.

Donepezil ( Aricept ), a cholinesterase inhibitor, is currently prescribed for mild to moderate stages of AD to improve memory and other cognitive functions.
Cholinesterase inhibitors work by delaying the breakdown of the neurotransmitter acetylcholine in the brain.
Acetylcholine helps communication between the nerve cells and is important for memory.

The research was funded in part by the National Institute on Aging ( NIA ) and was conducted as part of the Alzheimer's Disease Cooperative Study ( ADCS ), a nationwide clinical trials consortium supported by the NIA, a component of the National Institutes of Health, U.S. Department of Health and Human Services.

Source: The New England Journal of Medicine, 2005


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