Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months
Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months
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DOI：
10.1212/wnl.59.4.563
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发表时间：
2002-08-27
期刊：
影响因子：
9.9
通讯作者：
Nordberg, A
中科院分区：
文献类型：
--
作者：
Darreh-Shori, T;Almkvist, O;Nordberg, A
目的：研究卡巴拉汀对AD患者乙酰胆碱酯酶（ACNE）和丁酰胆碱酯酶（BuChE）的长期双重抑制作用。方法：11例轻度AD患者接受卡巴拉汀治疗12个月。用比色法测定脑脊液和血浆中胆碱酯酶（ChE）活性。免疫印迹分析用于评估ACNE亚型。在整个研究期间进行神经精神测试。结果如下：12个月时，利斯的明的平均剂量为8.6 mg/d，CSF中ChE的比活性低于基线值（ACNE降低36%，BuChE降低45%），与血浆中的平行降低相关（ACNE降低27%，BuChE降低33%）。CSF（而非血浆）中比活度的降低似乎取决于剂量和治疗持续时间。与记忆和注意力相关的一些神经心理学测试的分数与血浆和CSF ACNE和BuChE抑制长达6个月相关。免疫印迹分析显示“通读”痤疮异构体（ACNE-R）的上调，而突触异构体的水平不变。结论：卡巴拉汀可持续抑制CSF和血浆中的ACNE和BuChE。持续的CSF抑制与可逆性胆碱酯酶抑制剂他克林长期治疗后的早期结果形成对比，后者显示CSF中的ACNE活性增加，但血液中的ACNE活性未增加。卡巴拉汀对ACNE-R亚型优先上调的作用可能对疾病稳定有有利影响。
Objective: To study the long-term dual inhibitory effects of rivastigmine on acetylcholinesterase (ACNE) and butyrylcholinesterase (BuChE) in patients with AD. Methods: Eleven patients with mild AD received rivastigmine for 12 months. Cholinesterase (ChE) activities in the CSF and plasma were assessed colorimetrically. Immunoblot analysis was used to evaluate ACNE isoforms. Neuropsychiatric tests were performed throughout the study. Results: At 12 months, the mean dose of rivastigmine was 8.6 mg/d and specific activities of ChE in the CSF were lower than baseline values (by 36% for ACNE and 45% for BuChE), correlating with parallel reductions in the plasma (27% for ACNE and 33% for BuChE). The reduction of specific activities in the CSF, but not in the plasma, appeared to be dependent on the dose and duration of treatment. Scores of some of the neuropsychological tests associated with memory and attention were correlated with both plasma and CSF ACNE and BuChE inhibition for up to 6 months. Immunoblot analysis revealed up-regulation of the "read-through" ACNE isoform (ACNE-R), whereas levels of the synaptic isoform were unchanged. Conclusions: Rivastigmine causes persistent inhibition of ACNE and BuChE in CSF as well as plasma. The persistent CSF inhibition contrasts with earlier findings after long-term treatment by the reversible ChE inhibitor tacrine, which demonstrated increased ACNE activity in the CSF but not in the blood. Rivastigmine's effects on the preferential up-regulation of the ACNE-R isoform may have a favorable effect on disease stabilization.