卡德西尔
多奈哌齐
血管性痴呆
痴呆
临床痴呆评级
内科学
医学
认知功能衰退
安慰剂
临床终点
心理学
临床试验
疾病
病理
替代医学
作者
Martin Dichgans,Hugh S. Markus,Stephen Salloway,Auli Verkkoniemi,Margaret Moline,Qing Wang,Holly Posner,Hugues Chabriat
标识
DOI:10.1016/s1474-4422(08)70046-2
摘要
Cholinergic deficits might contribute to vascular cognitive impairment. Trials of cholinesterase inhibitors in patients with vascular dementia are difficult because of heterogeneous disease mechanisms and overlap between vascular and Alzheimer's disease (AD) pathology in the age-group recruited. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a genetic form of subcortical ischaemic vascular dementia. It represents a homogeneous disease process, and because of CADASIL's early onset, comorbid AD pathology is rare. We did a multicentre, 18-week, placebo-controlled, double-blind, randomised parallel-group trial to determine whether the cholinesterase inhibitor donepezil improves cognition in patients with CADASIL.168 patients with CADASIL (mean age 54.8 years) were assigned to 10 mg donepezil per day (n=86) or placebo (n=82) by a computer-generated randomisation protocol. Inclusion criteria included a mini-mental state examination (MMSE) score of 10-27 or a trail making test (TMT) B time score at least 1.5 SD below the mean, after adjustment for age and education. The primary endpoint was change from baseline in the score on the vascular AD assessment scale cognitive subscale (V-ADAS-cog) at 18 weeks. Secondary endpoints included scores on the ADAS-cog, MMSE, TMT A time and B time, Stroop, executive interview-25 (EXIT25), CLOX, disability assessment for dementia, and sum of boxes of the clinical dementia rating scale. Analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00103948.161 patients were analysed. There was no significant difference between donepezil (n=84) and placebo (n=77) in the primary endpoint. The least-squares mean change from baseline score was -0.81 (SE 0.59) in the placebo group and -0.85 (SE 0.57) in the donepezil group (p=0.956). There was a significant treatment effect favouring donepezil on the following secondary outcomes: TMT B time (p=0.023), TMT A time (p=0.015), and EXIT25 (p=0.022). Ten donepezil-treated patients discontinued treatment due to adverse events compared to seven placebo-treated patients.Donepezil had no effect on the primary endpoint, the V-ADAS-cog score in CADASIL patients with cognitive impairment. Improvements were noted on several measures of executive function, but the clinical relevance of these findings is not clear. Our findings may have implications for future trial design in subcortical vascular cognitive impairment.
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