| Summary: | 碩士 === 國立成功大學 === 臨床藥學研究所 === 88 === Background:
The prevalence of dementia among victims of ischemic stroke is as high as 24.6% after the first stroke and that of cognitive decline is 61.7%. Cerebral hypoperfusion after stroke is considered the cause of vascular dementia (VaD). Cholinesterase inhibitors（ChEI）can enhance cerebral blood flow in the ischemic area. In addition, the acetylcholine（ACh）concentration in cerebrospinal fluid of patients with VaD is lower than that of normal subjects and this fact is associated with cognition of these patients. Thus, the role of ACh in VaD may be important, and increasing the ACh concentration of brain in stroke and VaD patients may improve their cognition. Donepezil, a selective acetylcholinesterase inhibitor, results in cognition improvements in patients with Alzheimer''s disease when administrated 5 mg once daily. We made a hypothesis that using donepezil could improve the cognition in stroke patients.
Objective:
To evaluate the efficacy and safety of donepezil on cognition improvement in patients with ischemic stroke.
Methods:
The patients with ischemic stroke within three months were included in study. The study was a double-blind, parallel-group design and patients were random assigned to once-daily treatment with either donepezil 5 mg or placebo. The 11-week double-blind phase was followed by a 4-week single-blind placebo washout. The efficacy was measured by the Cognitive Ability Screening Instrument Chinese Version 2.0(CASI C-2.0), CASI estimated Mini-mental State Examination (MMSE-CE), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and Blessed Dementia Rating Scale (BDRS).
Results:
The study included 39 patients. Thirty-four patients completed the 11-week treatment and 33 patients completed the 15-week treatment. At week 11, the improvements in CASI C-2.0 and MMSE-CE were greater with donepezil than with placebo. The mean donepezil-placebo differences were 2.3 units in CASI C-2.0 (p=0.45) and 0.4 units in MMSE-CE (p=0.84). The mean changes in recent memory of CASI C-2.0 were 1.5 units with donepezil (p=0.006) and 0.8 units with placebo (p=0.37). The improvements in IQCODE and BDRS were greater with placebo than with donepezil. The mean donepezil-placebo differences were 0.04 units in IQCODE (p=0.24) and 0.5 units in BDRS (p=0.51). At week 15, the mean donepezil-placebo differences were 1.3 units in CASI C-2.0 (p=0.78), -0.12 units in IQCODE (p=0.79), -0.2 units in MMSE-CE (p=0.73) and 0.5 units in BDRS (p=0.46).
Eighteen patients (46%) had global cognition impairment at baseline. At week 11, there was a statistically significant change in CASI C-2.0 with donepezil (p=0.018). The improvement in CASI C-2.0 was greater with donepezil than with placebo, and the mean donepezil-placebo difference was 4.6 units (p=0.37). The improvements in MMSE-CE, IQCODE and BDRS were greater with placebo than with donepezil. The mean donepezil-placebo differences were -0.1 (p=0.67), 0.26(p=0.08) and 1.0 units (p=0.59), respectively. At week 15, the mean donepezil-placebo differences were 4.1 units in CASI C-2.0 (p=0.40), -0.2 units in MMSE-CE (p=0.91), 0.27 units in IQCODE (p=0.24) and 0.8 units in BDRS (p=0.32).
The incidence of adverse events in donepezil was 50% and in placebo was 42%. At week 11, there was a statistically significant reduction in fibrinogen with donepezil (p=0.008).
Conclusion:
Donepezil can improve recent memory in patients with ischemic stroke significantly. And, it can improve cognition in patients with global cognition impairment after ischemic stroke. Donepezil is a well-tolerated drug and may reduce the fibrinogen in patients with ischemic stroke.
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