That’s according to a recent article in the Journal of Alzheimer's Disease about the medication approved to treat patients with Alzheimer’s disease. The McGill University-led researchers report that donepezil could actually accelerate cognitive decline in people who carry the K-variant of butyrylcholinesterase (BChE-K) and urge more genetic testing before the drug is prescribed.
Donepezil, marketed as Aricept, is the most-prescribed medication for Alzheimer’s and often is used when mild cognitive impairment, a transitional state between normal age-related changes in cognition and dementia, is detected, according to background information in the report.
While the drug was tested as a possible treatment for mild cognitive impairment in a large, federally funded trial in 2005, the Alzheimer’s Disease Cooperative Study (ADCS), it was not approved by the FDA for that specific purpose, although physicians often prescribe it off-label.
“Genetic heterogeneity in amnestic mild cognitively impaired (aMCI) subjects could lead to variations in progression rates and response to cholinomimetic agents. Together with the apolipoprotein E4 (APOE-?4) gene, butyrylcholinesterase (BCHE) has become recently one of the few Alzheimer’s disease (AD) susceptibility genes with distinct pharmacogenomic properties,” the researchers point out.
In a re-analysis of the 2005 trial, 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.
“These results clearly emphasize the necessity of monitoring potential pharmacogenomic effects in this population of subjects, and suggest enrichment strategies for secondary prevention trials involving prodromal AD subjects,” study authors conclude.
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