According to a new study, the drug donepezil measurably slows the rate of brain shrinkage in some patients with mild cognitive impairment, a pre-Alzheimer's disease condition. The shrinkage was measured by magnetic resonance imaging (MRI).

Among carriers of the apolipoprotein E4 (APOE 4) allele, serial brain imaging studies of patients treated with donepezil showed less shrinkage of the hippocampus, a structure located at the base of the brain that is key for memory function, than for study patients who received placebo (no treatment). APOE 4 is a molecule involved in cholesterol metabolism and is a common genetic predisposition to Alzheimer's disease. All humans have a form of APOE, but APOE 4, which is present in 25 percent of the population, raises the likelihood of amyloid plaques forming in the brain, an important part of the pathology of Alzheimer's.

Findings will be presented July 17 at the Alzheimer's Association International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain.

"No drug has been shown to slow brain atrophy for patients with mild cognitive impairment," says Clifford Jack Jr., M.D., Mayo Clinic radiologist and lead study investigator. "Our study results seem to imply that donepezil does more than provide symptom relief -- it has an effect on a measure of brain health. Our findings also show that MRI measures can have usefulness in future studies of mild cognitive impairment."

The MRI study is an adjunct study to a previously published larger study of treatment of mild cognitive impairment patients with donepezil, Vitamin E or placebo, led by Ronald Petersen, M.D., Ph.D., Mayo Clinic neurologist. The larger study showed that donepezil slowed the rate of cognitive decline in patients with mild cognitive impairment.

The reason why there was an effect only in APOE 4 carriers remains unclear, according to Dr. Jack. "One possibility is that APOE 4 carriers were more likely to have definite Alzheimer's disease than noncarriers in the study who appear to have symptoms of early Alzheimer's disease, yet turn out to have a different diagnosis when an autopsy is performed after death," he explains.

Brain shrinkage is an essential component of Alzheimer's disease, says Dr. Jack. "In extreme cases, the brain of an Alzheimer's patient might weigh half of what a normal person's brain does at peak health."

No specific brain volume is diagnostic of Alzheimer's disease. The key, according to Mayo Clinic's Dr. Jack, is the rate of brain shrinkage relative to the volume at which a particular person's brain started.

Testing is required to know one is an APOE 4 carrier. However, experts in Alzheimer's disease do not recommend everyone undergo testing for APOE 4.

 

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