Querfurth H W, Allam G J, Geffroy M A, Schiff H B, Kaplan R F
Department of Neurology at St. Elizabeth's Medical Center, Boston, MA 02135, USA.
Dement Geriatr Cogn Disord. 2000 Nov-Dec;11(6):314-21. doi: 10.1159/000017260.
Dementia with Lewy bodies (DLB) is the second commonest form of dementia. The response to acetylcholinesterase inhibition (AChEI) could be greater in DLB than in Alzheimer's disease (AD) because cholineacetyl-transferase levels are more reduced in the former. This preliminary trial seeks to compare performances in cognitive tasks before and after tacrine administration in DLB and AD subjects.
Six DLB and 6 AD patients were enrolled in an open, nonrandomized, intervention trial using 80 mg/day tacrine. Patients met ADRDA or DLB consortium criteria for probable diseases. Subjects were matched for Mini Mental State Examination (MMSE) score, age and sex. Mattis Dementia Rating Scale (DRS), Controlled Oral Word Association Test (FAS) and Boston Naming tests were administered at baseline and at 6 months into treatment.
AD and DLB groups did not differ in initial mean total DRS scores. In the primary analysis, both groups declined during the course of treatment (-7.3 +/- 4.2 and -16.8 +/- 39.2 DRS points, respectively). Due to the large variability in DLB posttreatment scores, this group was divided post hoc into responders (DLBr) and nonresponders (DLBnr). The DLBr group outperformed the DLBnr group at baseline (p < 0.05) and, notably, in follow-up DRS test scores (p < 0.001). Two-way MANOVA comparing both DLB subgroups with either the entire AD cohort or similarly stratified AD subgroups showed a significant interaction (F = 7.6; p < 0.015), attributed mostly to declines in DLBnr group scores (p < 0.01). Surprisingly, on DRS memory subscale and FAS tests, there were significant improvements in DLBr scores (p < 0.02). A baseline MMSE (or DRS memory) score >/=15 predicted a positive response to tacrine in DLB. Acceleration of parkinsonism occurred in all DLB subjects.
Results from a primary analysis of the therapeutic effect of 80 mg/day tacrine in DLB and AD were negative. However, post hoc analysis showed that mild to moderate DLB responds favorably to AChEI relative to AD through stabilization of global cognitive decline and improvements in specific cognitive areas. These results could be useful in the planning of a more definitive study.
路易体痴呆（DLB）是第二常见的痴呆类型。DLB对乙酰胆碱酯酶抑制（AChEI）的反应可能比对阿尔茨海默病（AD）的反应更大，因为前者的胆碱乙酰转移酶水平降低得更多。这项初步试验旨在比较DLB和AD受试者服用他克林前后在认知任务中的表现。
6名DLB患者和6名AD患者参加了一项开放、非随机的干预试验，使用80毫克/天的他克林。患者符合ADRDA或DLB联盟可能疾病的标准。受试者在简易精神状态检查表（MMSE）评分、年龄和性别方面进行了匹配。在基线和治疗6个月时进行马蒂斯痴呆评定量表（DRS）、受控口语单词联想测验（FAS）和波士顿命名测试。
AD组和DLB组的初始平均DRS总分无差异。在初步分析中，两组在治疗过程中均有所下降（分别下降-7.3±4.2和-16.8±39.2个DRS点）。由于DLB治疗后评分差异较大，该组事后被分为反应者（DLBr）和无反应者（DLBnr）。DLBr组在基线时（p < 0.05）以及在随访DRS测试评分中（p < 0.001）的表现均优于DLBnr组。将DLB的两个亚组与整个AD队列或类似分层的AD亚组进行双向多变量方差分析显示存在显著交互作用（F = 7.6；p < 0.015），这主要归因于DLBnr组评分的下降（p < 0.01）。令人惊讶的是，在DRS记忆子量表和FAS测试中，DLBr组的评分有显著改善（p < 0.02）。基线MMSE（或DRS记忆）评分≥15预测DLB患者对他克林有阳性反应。所有DLB受试者均出现帕金森症状加速现象。
对80毫克/天他克林在DLB和AD中的治疗效果进行的初步分析结果为阴性。然而，事后分析表明，相对于AD，轻度至中度DLB通过稳定整体认知衰退和改善特定认知领域，对AChEI反应良好。这些结果可能有助于规划更具确定性的研究。
