Study proves concept: Treatment can delay transition to Alzheimer's
A large study shows donepezil (Aricept) can temporarily delay the risk of developing Alzheimer's disease for individuals with mild cognitive impairment (MCI), marking the first time any drug has been shown to postpone the transition from MCI to Alzheimer's. These findings were presented at the annual meeting of the American Academy of Neurology and will be published online April 14 in the New England Journal of Medicine.
The delay for those taking donepezil was modest, lasting for only the first 12 months of a three-year clinical trial. Vitamin E, the other study drug, showed no significant benefit at any point. Still, Alzheimer experts expressed optimism that the study provides an important proof of concept that will set the stage for testing future drugs with potentially greater effect. Results also demonstrate success in the medically challenging process of identifying individuals with MCI and monitoring their status in a large, multi-site clinical trial. MCI is a difficult-to-diagnose condition that often represents an intermediate stage between normal function and dementia.
"This study may be pivotal in shifting our sights toward altering the Alzheimer's disease process as early as possible, buying time and preserving function for those who may later develop dementia," says Ronald C. Petersen, M.D., Ph.D., lead study investigator as well as professor of neurology at the Mayo Clinic College of Medicine in Rochester, Minn., and director of Mayo's Alzheimer's Disease Center. Petersen also serves on the Alzheimer's Association Medical and Scientific Advisory Council.
The three-year Memory Impairment Study enrolled more than 750 older adults who met criteria for "amnestic MCI," in which individuals have measurable memory difficulties greater than expected for their age and education but no reduction in overall ability to function. Participants were randomly assigned to one of three daily regimens: 10 milligrams of donepezil (Aricept), 2,000 international units of vitamin E or a placebo (inactive treatment). Investigators administered regular tests to determine whose symptoms had progressed to meet criteria for Alzheimer's disease as well as to monitor performance in various types of mental function.
Participants receiving donepezil had a reduced risk of developing Alzheimer's disease during the first year of the trial, but by the end of the study their risk was the same as those taking vitamin E or the placebo.
According to the study authors, approximately 80 percent of individuals who meet diagnostic criteria for amnestic MCI will develop Alzheimer's disease within six years.
The authors note their findings are not strong enough to support a clear recommendation to treat MCI with donepezil, but the results "could prompt a discussion between the clinician and the patient about this possibility."
The study found donepezil reduced risk of progressing to Alzheimer's for two to three years for one group: those with a genetic variation called APOE-4, which has been linked to an increased risk of developing Alzheimer's disease. The researchers are not, however, recommending genetic testing for individuals with MCI.
Donepezil is currently approved by the U.S. Food and Drug Administration (FDA) to treat symptoms of mild to moderate Alzheimer's disease. Its benefit in treating Alzheimer's is also modest, often described as postponing progression for an average of six months for some, but not all, individuals.
The study, which was funded by the National Institute on Aging (NIA), Eisai Europe, Ltd and Pfizer Inc, will also be published in the June 9, 2005, print version of the New England Journal of Medicine.
For more information, please see:
- Alzheimer's Association fact sheet on MCI
- Alzheimer's Association fact sheet on cholinesterase inhibitors, the class of Alzheimer drugs that includes donepezil