23 February 2017
Donepezil, a medication that is approved to treat people with Alzheimer’s disease, should not be prescribed for people with mild cognitive impairment without a genetic test. UCLA School of Nursing researchers discovered that for people who carry a specific genetic variation — the K-variant of butyrylcholinesterase, or BChE-K — donezpezil could accelerate cognitive decline.
Mild cognitive impairment is a transitional state between normal age-related changes in cognition and dementia. Because many people with the condition display symptoms similar to those caused by Alzheimer’s disease, some physicians prescribe donepezil, which is marketed under the brand name Aricept and is the most-prescribed medication for Alzheimer’s.
Donepezil was tested as a possible treatment for mild cognitive impairment in a large, federally funded study published in 2005, but it was not approved by the FDA. Still, doctors have often prescribed the drug “off-label” — meaning that it is not approved for that specific disorder — for their patients with mild cognitive impairment.
From data collected during the 2005 trial, the researchers looked at the association between BChE-K and changes in cognitive function. Using two tests that measure cognitive impairment, the Mini-Mental State Examination and the Clinical Dementia Rating Sum of Boxes, they found that people with the genetic variation who were treated with donepezil had greater changes in their scores than those who took placebos. They also found that those who took donepezil had a faster cognitive decline than those who took the placebo.
Physicians are increasingly using personalized medicine, including pharmacogenetics — the study of how genetics affect a person’s response to a drug — to tailor their patients’ care. The findings reinforce the importance of physicians discussing the possible benefits and risks of this treatment with their patients.
The study was led by Sophie Sokolow, an associate professor at the UCLA School of Nursing. Co-authors were Ziaohui Li, Lucia Chen, Kent Taylor and Jerome Rotter, all of UCLA.
The study was published in the Journal of Alzheimer’s Disease.
Sokolow S, Li X, Chen L, Taylor KD, Rotter JI, Rissman RA, Aisen PS, Apostolova LG (2017) Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment. J Alzheimers Dis 56, 229-237.
The work was supported by the National Institute on Aging (grant 1K23AG05141601A1).