Alzheimers Disease Drug May Speed Cognitive Decline in Some Patients


Donepezil could quicken cognitive decline in patients with a BChE-K mutation.

A drug used to treat Alzheimer’s disease may pose harm for patients prescribed the drug off-label to treat mild cognitive impairment.

When treated with the drug donepezil (Aricept), patients with the K-variant of butyrylcholinesterase (BChE-K) could experience accelerated cognitive decline, according to a new study published by the Journal of Alzheimer’s disease.

The study authors said patients with mild cognitive impairment should undergo genetic testing prior to treatment with donepezil to prevent serious disease progression related to a genetic mutation.

Mild cognitive impairment is a state between normal age-related cognitive decline and dementia. This condition is characterized by problems with memory, language, thinking, and judgement that are more advanced than changes seen with normal aging. These changes typically are not severe enough to impact day-to-day activities, but may increase the risk of progressing to dementia, the Mayo Clinic reported.

Since many patients with the condition present symptoms similar to Alzheimer’s disease, physicians tend to prescribe drugs that treat the disease, including donepezil, according to the study. Donepezil is central acetylcholinesterase inhibitor, and is the most commonly prescribed Alzheimer’s disease drug.

While donepezil was previously tested in a large clinical trial of patients with mild cognitive impairment, the drug never received regulatory approval in this population. However, physicians often prescribe the drug off-label to patients with mild cognitive impairment.

Using data from the previously conducted clinical trial, the investigators examined the link between BChE-K and alterations in cognitive function. They used the Mini-Mental State Examination and the Clinical Dementia Rating Sum of Boxes to measure the level of cognitive impairment.

The study authors found that patients with the genetic variant who were treated with donepezil had substantially larger changes in their cognitive scores, compared with those taking placebo, according to the study.

The investigators also discovered that patients who took the drug had faster cognitive decline, compared with those treated with placebo. This suggests that patients with the BChE-K mutation may be adversely impacted by treatment with donepezil, according to the study.

Physicians are largely implementing personalized medicine to improve patient care and outcomes. The study results suggest that physicians should discuss the benefits and risks of treatment with donepezil for these patients, and potentially explore alternate treatment options, the study concluded.

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