Scholarship and Research

May 2, 2005
Drug, early treatment can slow onset of Alzheimer’s disease

BY janet Christenbury

In an important finding about the ability of drugs to prevent or delay the onset of Alzheimer’s disease, a group of physicians at Alzheimer’s research centers throughout the nation found that patients with a type of mild cognitive impairment characterized by memory loss who are treated with donepezil (brand name Aricept) had a lower rate of progression to symptoms of Alzheimer’s disease during the early part of treatment.

This effect was extended in patients with genetic variations associated with risk for Alzheimer’s disease. The study also found that vitamin E had no benefit in delaying the disease. The study, supported by the National Institutes of Health, is published online in the New England Journal of Medicine and will appear in the journal’s June 9 print issue.

Allan Levey, professor and chair of neurology and director of the Emory Alzheimer’s Disease Research Center, led the Emory component of the study, which was conducted by the Alzheimer’s Disease Cooperative Study Group and led by Ronald Petersen of the Mayo Clinic College of Medicine.

Patients with mild cognitive impairment (MCI) experience memory loss but do not have clinical symptoms of Alzheimer’s disease, and they are able to function independently. Approximately 10–15 percent of patients with MCI progress to Alzheimer’s within a year, and 40–50 percent develop the disease within three years. Only 1–2 percent of elderly people without MCI develop Alzheimer’s disease each year. The rate of progression is higher in patients with certain genetic variations in the apolipoprotein (APOE) gene.

Donepezil is a type of drug called a cholinesterase inhibitor, commonly prescribed for patients with mild to moderate Alzheimer’s disease. Cholinesterase inhibitors are designed to enhance memory and other cognitive functions by influencing chemical activities in the brain to compensate for the loss of functioning brain cells.

An earlier study by the Alzheimer’s co-op study group showed that treatment with the antioxidant vitamin E could delay disease progression in patients with moderate to severe Alzheimer’s; the current study was designed to find out whether vitamin E or donepezil could delay the clinical diagnosis of Alzheimer’s disease in patients with MCI characterized by memory loss.

In conducting the double-blind, three-year study, physicians assigned 769 patients with MCI to three study groups. One group received vitamin E daily, a second group received donepezil daily, and a third group received placebo. Of the total patients enrolled in the study, 212 developed possible or probable Alzheimer’s disease over the three-year period. The overall rate of progression from MCI to Alzheimer’s was
16 percent per year.

At the end of the three-year study, the researchers found no significant differences in the progression to Alzheimer’s disease among the vitamin E group, the donepezil group and the placebo group. However, 12 months into the project, the donepezil group did have a reduced likelihood of progression to Alzheimer’s disease.

Although this effect disappeared in most patients by 18 months, the reduction in rate of progression remained throughout the three-year follow-up period for individuals with the genetically variant APOE alleles. The findings revealed a strong correlation between APOE alleles and progression to Alzheimer’s disease, with 76 percent of the cases of progression to Alzheimer’s disease occurring in these genetic carriers.

“This study shows that it may be very important to identify individuals with MCI in order to begin early treatment with available drugs or others currently under development,” Levey said. “Because the brain is likely already seriously affected by the disease process by the time MCI symptoms are noticeable, earlier identification of disease would allow treatment to be initiated even sooner.

“Although our results did not show that [donepezil] actually changes the underlying disease, it did delay onset of symptoms,” he continued. “This is the first study to demonstrate any ability to slow the clinical progression from MCI to Alzheimer’s disease.”

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