Clinica Neurologica, Ospedale S. Maria della Misericordia, Università degli studi di Perugia, Perugia, Italy.
Acta Neurol Scand. 2011 Aug;124(2):122-9. doi: 10.1111/j.1600-0404.2010.01435.x. Epub 2010 Sep 29.
To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs).
Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1- year treatment.
Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment.
AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
测量来自三个欧洲中心的阿尔茨海默病（AD）患者在接受随机临床试验时的脑脊液（CSF）乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的活性，这些患者在接受不同的乙酰胆碱酯酶抑制剂（AChEIs）长期治疗前后。
在这项研究中，纳入了 144 名患者，其中 104 名患者接受了多奈哌齐治疗，15 名患者接受了加兰他敏治疗，16 名患者接受了利伐斯的明治疗，9 名患者接受了安慰剂治疗。在基线和治疗 1 年后，测量了 CSF 中的 AChE 和 BChE 活性。
在随访中，多奈哌齐和加兰他敏组的 CSF AChE 活性显著增加，而 BChE 活性没有变化；在多奈哌齐组中，记录到了血浆浓度与 AChE 活性之间的正相关。相反，在利伐斯的明组中，两种酶的 CSF 活性均下降。在考虑的任何一组中，CSF AChE 和 BChE 活性均与临床结果无关。治疗后 CSF 生物标志物没有任何变化。
AChEIs 以与药效学作用无关的方式，对 CSF 中靶酶的活性产生不同的影响。
