Neurologists may have foot in the door to preventing Alzheimer’s before it starts

Apr 13 2005

A study led by Mayo Clinic shows for the first time that a drug appears to have a slowing effect -- though limited -- on the progression from mild cognitive impairment to Alzheimer's disease. The findings will be published online in the New England Journal of Medicine on April 14.

"Our findings represent an important shift in the field of Alzheimer's disease treatment, in that this is the only study to date to demonstrate the ability to push back the clinical diagnosis of the disease," says Ronald Petersen, M.D., Ph.D., Mayo Clinic neurologist and lead investigator of the trial. "This may be the sign of new horizons to come in attempting to alter the Alzheimer's disease process as early as possible, buying time for those who may later progress."

Dr. Petersen and his co-investigators are optimistic about these findings and what they represent. Rather than focusing on the effects of the particular drugs tested, Dr. Petersen indicates he is enthusiastic about the underlying concept -- causing any amount of postponement in the heretofore unstoppable progression of Alzheimer's disease. "This study may be the front-runner in shifting our sights toward earlier treatment of the Alzheimer's process, laying the groundwork for testing other drugs," says Dr. Petersen. "Mild cognitive impairment patients are a great population of people to target, hopefully with other treatments as well."

This randomized, double-blind, placebo-controlled, multicenter study compared vitamin E; donepezil, an Alzheimer's treatment drug; and placebo for delay or prevention of progression to Alzheimer's disease in mild cognitive impairment patients. These patients had the amnesic (memory-related) variety of mild cognitive impairment, a transitional stage between the forgetfulness of normal aging and the more serious memory decline and other problems associated with Alzheimer's disease.

Over the first year of the three-year trial, mild cognitive impairment patients treated with donepezil had a reduced risk of progressing to Alzheimer's disease compared to patients who took placebo, an inactive pill. Although the patients treated with donepezil initially progressed to Alzheimer's disease at a slower rate than patients treated with vitamin E or placebo, the risk of progression to Alzheimer's disease was the same among all three treatment groups by the end of the study. Vitamin E had no effect on slowing the progression to Alzheimer's disease over the course of the study.

The study found one subset of patients for whom the effect of the donepezil treatment lasted longer, up to two to three years: those possessing a particular genotype called Apolipoprotein E4. Previous studies have shown those with Apolipoprotein E4 genotype have a higher propensity to develop Alzheimer's than the general population.

The investigators are not recommending genotyping, or administering tests to determine genetic makeup of patients with mild cognitive impairment. In addition, while they are not recommending treatment with donepezil for all mild cognitive impairment patients, Dr. Petersen indicates that the findings of this study open the door for discussion of donepezil treatment on an individual basis for patients with mild cognitive impairment. For example, donepezil might be considered as an option for mild cognitive impairment patients who want an aggressive approach, he explains.

This study involved 769 participants at 69 medical centers in the United States and Canada. The National Institute on Aging funded this study with additional support from Pfizer, Eisai and DSM Nutritional Products.

http://www.mayo.edu/