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Mild cognitive impairment, no benefit from Donepezil after three years

Researchers of the Alzheimer's Disease Cooperative Study evaluated the effect of Vitamin E and Donepezil, an acetylcholinesterase inhibitor, in the progression from mild cognitive impairment ( MCI ) to Alzheimer’s disease.

Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease.

Subjects with mild cognitive impairment were randomly assigned to receive 2000 IU of Vitamin E daily, 10 mg of Donepezil daily, or placebo for three years.

A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212.
The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year.

As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the Vitamin E group or the Donepezil group during the three years of treatment.

Analyses of the treatment effects showed that as compared with the placebo group, the Donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04).

Among carriers of one or more apolipoprotein E 4 alleles, the benefit of Donepezil was evident throughout the three-year follow-up.

The Authors conclude: “ Vitamin E had no benefit in patients with mild cognitive impairment. Although Donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with Donepezil than among those given placebo. “

Petersen RC et al, N Engl J Med 2005; 352: 2379-2388


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