Donepezil in the Treatment of Vascular Dementia

Clinical Question

Is donepezil effective in the treatment of vascular dementia?

Evidence-Based Answer

Donepezil in a dosage of 10 mg daily provides a small benefit in patients with mild to moderate vascular dementia and generally is well tolerated.

Practice Pointers

Donepezil, a cholinesterase inhibitor, is somewhat effective in the treatment of mild to moderate cognitive impairment caused by Alzheimer’s disease. Malouf and Birks examined the evidence from two similar manufacturer-sponsored studies of donepezil in a total of 1,219 patients with vascular cognitive impairment (sometimes called “multi-infarct dementia” or “vascular dementia”). Both studies were randomized, double blinded, and placebo controlled. Validated diagnostic criteria were used to identify patients with probable vascular dementia. Given the challenge of diagnosing dementia subtypes before death, however, a substantial number of patients probably had mixed vascular and Alzheimer’s dementia.¹

Patients who took donepezil performed slightly better on tests of cognitive function, such as the Mini-Mental State Examination (weighted mean difference, 1.2 points at 24 weeks on this 30-point scale) and the Alzheimer’s Disease Assessment Scale cognitive subscale. Patients who took the 10-mg dosage did better than those who took the 5-mg dosage. Patients who took the 10-mg dosage (but not the 5-mg dosage) also did better than control patients on the Clinical Dementia Rating scale. There was no difference between groups on the Alzheimer’s Disease Functional Assessment and Change Scale, which focuses on activities of daily living. Compared with the lower dosage and placebo, the 10-mg dosage was associated with more adverse events (odds ratio for at least one adverse event, 1.95; 95 percent confidence interval, 1.20 to 3.15;P = .007). Most adverse events were minor, and the pooled dropout rate and the rate of severe adverse events were similar between groups.