Objective: The objective of these studies was to investigate the efficacy and tolerability of the selective acetylcholinesterase inhibitor, donepezil, in vascular dementia (VaD) patients.
Background: VaD accounts for approximately 10-20% of all dementia cases. There are currently no approved treatments for the symptoms of VaD. However, there is evidence that patients with VaD exhibit a cholinergic deficit and may therefore benefit from treatment with the potent and selective acetylcholinesterase inhibitor, donepezil.
Design: Combined analysis of efficacy data from two 24-week, randomized, double-blind, placebo-controlled, parallel-group studies (with identical protocols) of donepezil (5 or 10 mg/day) in patients with probable or possible VaD.
Materials and Methods: A diagnosis of probable or possible VaD of >3 months’ duration was required (according to NINDS-AIREN criteria) for enrolment. Patients with a prior diagnosis of Alzheimer’s disease (AD) and subsequent cognitive impairment due to stroke or other cerebrovascular disease were excluded. Patients were randomized to receive placebo, donepezil 5 mg/day, or donepezil 10 mg/day (5 mg/day for the first 28 days and 10 mg/day thereafter). Efficacy measures included the Alzheimer’s Disease Assessment Subscale-cognitive subscale (ADAS-cog); the Clinician’s Interview-Based Impression of Change-plus version (CIBIC-plus); the Clinical Dementia Rating-Sum of the Boxes (CDR-SB); and the Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS). Results are reported for intent-to-treat observed cases, least-squares mean change from baseline at Week 24.
Results: Of 1219 enrolled patients (392 placebo, 406 donepezil 5 mg/day, 421 donepezil 10 mg/day), 73% had probable VaD and 27% had possible VaD. Both donepezil-treated groups showed significant improvements in cognitive function compared with placebo (ADAS-cog: placebo, -0.10; donepezil 5 mg/day, -1.89, P<0.001; donepezil 10 mg/day, -2.38, P<0.001). Greater improvements in global function were observed with both donepezil groups than with the placebo group both in the CIBIC-plus (% patients showing minimal, moderate, or marked improvement: placebo, 29%; donepezil 5 mg/day, 41%, P<0.001; donepezil 10 mg/day, 33%, P=0.07; overall treatment, P=0.001), and on the CDR-SB (placebo, 0.10; donepezil 5 mg/day, -0.11, P=0.11; donepezil 10 mg/day, -0.33, P=0.002). Ability to perform activities of daily living (ADLs) was maintained in both donepezil-treated groups, compared with a decline in the placebo-treated group with significant treatment benefits observed (ADFACS: placebo, 0.82; donepezil 5 mg/day, -0.19, P=0.02; donepezil 10 mg/day, -0.19, P=0.02).
Conclusion:Donepezil-treated patients with probable or possible VaD demonstrated significant benefits in cognition and global function compared with placebo-treated patients. In addition, donepezil-treated patients showed significant benefits on ability to perform ADLs, thus donepezil treatment may also help to delay functional decline in patients with VaD. Donepezil was well tolerated in this population, which has a high incidence of cardiovascular disease. These results indicate that donepezil may have an important role in the management of patients with VaD.
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