卡巴拉汀用于帕金森病所致痴呆。

Rivastigmine for dementia associated with Parkinson's disease.

作者信息

Emre Murat, Aarsland Dag, Albanese Alberto, Byrne E Jane, Deuschl Günther, De Deyn Peter P, Durif Franck, Kulisevsky Jaime, van Laar Teus, Lees Andrew, Poewe Werner, Robillard Alain, Rosa Mario M, Wolters Erik, Quarg Peter, Tekin Sibel, Lane Roger

机构信息

Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

出版信息

N Engl J Med. 2004 Dec 9;351(24):2509-18. doi: 10.1056/NEJMoa041470.

DOI:10.1056/NEJMoa041470

PMID:15590953

Abstract

BACKGROUND

Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients.

METHODS

Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer's Disease Cooperative Study-Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini-Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test.

RESULTS

A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer's disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01).

CONCLUSIONS

In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson's disease but also with higher rates of nausea, vomiting, and tremor.

摘要

背景

胆碱能缺陷在患有帕金森病相关痴呆的患者中很突出。我们研究了双重胆碱酯酶抑制剂卡巴拉汀对此类患者的影响。

方法

在临床诊断为帕金森病至少2年后出现轻度至中度痴呆的患者被随机分配接受安慰剂或每天3至12毫克卡巴拉汀，为期24周。主要疗效变量是阿尔茨海默病评估量表认知分量表（ADAS-cog）和阿尔茨海默病协作研究-临床医生对变化的整体印象（ADCS-CGIC）的评分。次要临床结局是阿尔茨海默病协作研究-日常生活活动量表、10项神经精神症状量表、简易精神状态检查表、认知药物研究注意力测试、语言流畅性测试和十点画钟测试的评分。

结果

共纳入541例患者，410例完成研究。接受卡巴拉汀治疗的患者的结局优于接受安慰剂的患者；然而，这两组之间的差异中等，与卡巴拉汀治疗阿尔茨海默病的试验中报告的差异相似。卡巴拉汀治疗的患者在70分的ADAS-cog评分上平均改善2.1分，基线评分为23.8分，而安慰剂组从基线评分24.3分恶化0.7分（P<0.001）。在卡巴拉汀组19.8%的患者和安慰剂组14.5%的患者中观察到ADCS-CGIC评分有临床意义的改善，分别有13.0%和23.1%的患者出现临床意义的恶化（24周时平均评分分别为3.8和4.3；P=0.007）。在所有次要疗效变量方面，卡巴拉汀的结局明显更好。最常见的不良事件是恶心（卡巴拉汀组29.0%的患者和安慰剂组11.2%的患者，P<0.001）、呕吐（16.6%和1.7%，P<0.001）和震颤（10.2%和3.9%，P=0.01）。