Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.
Lancet Neurol. 2010 Oct;9(10):969-77. doi: 10.1016/S1474-4422(10)70194-0. Epub 2010 Aug 20.
Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB).
Patients (≥50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day) according to a computer-generated list. Patients and all physicians who had contact with them were masked to treatment assignment. No primary endpoint was defined. Safety analyses were done for all patients who took at least one dose of memantine or placebo, and efficacy analyses were done for all patients who had at least one valid postbaseline assessment. This trial is registered with ClinicalTrials.gov, number NCT00855686.
Of the 199 patients randomly assigned to treatment, 34 with DLB and 62 with PDD were given memantine, and 41 with DLB and 58 with PDD were given placebo. 159 (80%) patients completed the study: 80 in the memantine group and 79 in the placebo group. 93 patients treated with memantine and 97 patients treated with placebo were included in the efficacy analysis. At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo (mean change from baseline 3·3 vs 3·9, respectively, difference -0·6 [95% CI -1·2 to -0·1]; p=0·023). No significant differences were noted between the two treatments in patients with PDD (3·6 with memantine vs 3·8 with placebo, -0·1 [-0·6 to 0·3]; p=0·576) or in the total population (3·5 with memantine vs 3·8 with placebo, -0·3 [-0·7 to 0·1]; p=0·120). Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group (-4·3 vs 1·7, respectively, -5·9 [-11·6 to -0·2]; p=0·041) in patients with DLB, but not in those with PDD (-1·6 vs -0·1, respectively, -1·4 [-5·9 to 3·0]; p=0·522) or in the total patient population (-2·6 vs 0·4, respectively, -2·9 [-6·3 to 0·5]; p=0·092). In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations. The incidence of adverse events and number of discontinuations due to adverse events were similar in the two groups. The most common serious adverse events were stroke (n=3 in memantine group), falls (n=2 in memantine group; n=1 in placebo group), and worsening of dementia (n=2 in memantine group).
Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients.
Lundbeck.
先前的研究表明，与路易体相关的痴呆症患者可能受益于 N-甲基-D-天冬氨酸受体拮抗剂美金刚的治疗，但需要更多的数据。因此，我们对美金刚治疗轻度至中度帕金森病痴呆（PDD）或路易体痴呆（DLB）患者的疗效和安全性进行了研究。
我们从奥地利、法国、德国、英国、希腊、意大利、西班牙和土耳其的 30 个专科中心招募了年龄≥50 岁的轻度至中度 PDD 或 DLB 患者。他们根据计算机生成的列表随机分配至安慰剂或美金刚（每天 20mg）组。患者和所有与他们接触过的医生都对治疗分配进行了盲法。未定义主要终点。对至少服用一剂美金刚或安慰剂的所有患者进行了安全性分析，对至少有一次有效基线后评估的所有患者进行了疗效分析。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT00855686。
在 199 名随机接受治疗的患者中，34 名患有 DLB，62 名患有 PDD 的患者接受了美金刚治疗，41 名患有 DLB，58 名患有 PDD 的患者接受了安慰剂治疗。159 名（80%）患者完成了研究：美金刚组 80 名，安慰剂组 79 名。93 名接受美金刚治疗的患者和 97 名接受安慰剂治疗的患者被纳入疗效分析。在第 24 周，接受美金刚治疗的 DLB 患者根据阿尔茨海默病合作研究（ADCS）-临床总体印象变化评分显示出比接受安慰剂治疗的患者更大的改善（分别为基线变化 3.3 与 3.9，差值 -0.6 [95%CI -1.2 至 -0.1]；p=0.023）。在 PDD 患者（美金刚组为 3.6，安慰剂组为 3.8，差值 0.1 [-0.6 至 0.3]；p=0.576）或总人群（美金刚组为 3.5，安慰剂组为 3.8，差值 -0.3 [-0.7 至 0.1]；p=0.120）中，两种治疗方法之间没有显著差异。在接受美金刚治疗的 DLB 患者中，神经精神问卷评分显示出显著更大的改善（美金刚组为 -4.3，安慰剂组为 1.7，差值 -5.9 [-11.6 至 -0.2]；p=0.041），但在接受 PDD 治疗的患者中（美金刚组为 -1.6，安慰剂组为 -0.1，差值 -1.4 [-5.9 至 3.0]；p=0.522）或总患者人群中（美金刚组为 -2.6，安慰剂组为 0.4，差值 -2.9 [-6.3 至 0.5]；p=0.092）则没有。在大多数认知测试评分、ADCS-日常生活活动评分和 Zarit 照顾者负担评分中，在任何研究人群中，两组治疗之间都没有显著差异。两组的不良事件发生率和因不良事件而停药的人数相似。最常见的严重不良事件是中风（美金刚组 3 例）、跌倒（美金刚组 2 例，安慰剂组 1 例）和痴呆恶化（美金刚组 2 例）。
美金刚似乎可以改善轻度至中度 DLB 患者的整体临床状况和行为症状，可能是治疗这些患者的一种选择。
Lundbeck。
