University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536-0230, USA.
CNS Neurosci Ther. 2010 Dec;16(6):330-6. doi: 10.1111/j.1755-5949.2010.00182.x. Epub 2010 Oct 15.
Rivastigmine is approved in the USA for the treatment of mild to moderate Alzheimer's disease and Parkinson's disease dementia (PDD). Executive function (EF) deficits are a core symptom of PDD. The current objective was to investigate the effects of rivastigmine capsules versus placebo on EF in PDD, focusing on secondary outcome measures from a large, international, randomized, double-blind, placebo-controlled, 24-week trial (EXPRESS, CENA713B2311).
Secondary outcomes included Delis-Kaplan Executive Function System (D-KEFS) measures of EF. Data from three D-KEFS subtests (Card Sorting, Letter Fluency, Color-Word Interference), plus the Symbol Digit Modalities Test were analyzed in the observed case (OC) population. Changes from baseline in the rivastigmine versus placebo groups were evaluated using the van Elteren test blocking for country.
Of 541 patients in the EXPRESS study, 402, 71, 97, and 65 patients provided data for Letter Fluency, Card Sorting and Color-Word Interference subtests, and the Symbol Digit Modalities Test, respectively. On Letter Fluency, rivastigmine was associated with improvements in correct responses, set loss errors, and responses made (all P < 0.05), but not repetition errors. Higher Card Sorting recognition description score (P= 0.03), and more correct substitutions on the Symbol Digit Modalities Test (P= 0.02) were also recorded.
Rivastigmine was associated with significant improvements over placebo on EF tests evaluating flexibility of thinking, problem solving and planning in patients with PDD. These findings support the hypothesis that rivastigmine may affect frontal subcortical circuits, which potentially contributes to observed clinical improvement associated with EF.
卡巴拉汀胶囊在美国被批准用于治疗轻度至中度阿尔茨海默病和帕金森病痴呆（PDD）。执行功能（EF）缺陷是 PDD 的核心症状。本研究旨在研究卡巴拉汀胶囊与安慰剂对 PDD 患者 EF 的影响，重点关注大型国际随机双盲安慰剂对照 24 周试验（EXPRESS，CENA713B2311）的次要结局测量。
次要结局包括 Delis-Kaplan 执行功能系统（D-KEFS）的 EF 测量。在观察性病例（OC）人群中分析了来自三个 D-KEFS 子测试（卡片分类、字母流畅性、颜色-单词干扰）以及符号数字模态测试的数据。使用范埃伦滕测试对组间进行阻滞，根据国家评估卡巴拉汀与安慰剂组之间从基线的变化。
在 EXPRESS 研究的 541 名患者中，402、71、97 和 65 名患者分别提供了字母流畅性、卡片分类和颜色-单词干扰子测试以及符号数字模态测试的数据。在字母流畅性方面，卡巴拉汀与正确反应、集失错误和反应次数的改善相关（均 P<0.05），但与重复错误无关。更高的卡片分类识别描述评分（P=0.03）和符号数字模态测试中更多的正确替代（P=0.02）也被记录下来。
卡巴拉汀与安慰剂相比，在评估 PDD 患者思维灵活性、解决问题和计划能力的 EF 测试中，显著改善。这些发现支持了卡巴拉汀可能影响额叶皮质下回路的假设，这可能有助于观察到与 EF 相关的临床改善。
