Brain proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer's disease: changes after treatment with xanomeline, an M1 selective cholinergic agonist.
Brain proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer's disease: changes after treatment with xanomeline, an M1 selective cholinergic agonist.
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阿尔茨海默病中的脑质子磁共振波谱 (1H-MRS)：用 Xanomeline（一种 M1 选择性胆碱能激动剂）治疗后的变化。
DOI：
10.1176/ajp.154.10.1459
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Renshaw,PF
中科院分区：
文献类型：
--
作者：
Satlin,A;Bodick,N;Offen,WW;Renshaw,PF
目的在阿尔茨海默病患者死后脑组织中发现磷脂分解代谢中间体甘油磷酸胆碱的细胞水平高于正常细胞水平。质子磁共振波谱 (1H-MRS) 可以检测主要由甘油磷酸胆碱引起的胆碱共振。作者检验了这样的假设：xanomeline（一种 M1 选择性毒蕈碱胆碱能激动剂）治疗与 1H-MRS 胆碱共振降低相关。方法 患有轻度至中度阿尔茨海默病的患者接受安慰剂或 xanomeline 治疗 6 个月。 12 名患者在基线时和治疗停止后收集了 1H-MRS 谱，其中 2 名患者服用安慰剂，10 名患者服用 xanomeline，剂量为 25 mg tid (N= 4)、50 mg tid (N= 3) 或 75 mg tid (N= 3)。 结果 对于服用 xanomeline 的联合组患者，胆碱/肌酸比从基线到结论 使用胆碱能激动剂治疗阿尔茨海默病与 MRS 胆碱共振的降低有关。 Xanomeline 可以通过减少细胞对乙酰胆碱合成的游离胆碱的需求来减少胆碱能神经元膜的分解。
ObjectiveHigher than normal cellular levels of the phospholipid catabolic intermediate glycerophosphocholine have been found in postmortem brain tissue of persons with Alzheimer’s disease. Proton magnetic resonance spectroscopy (1H-MRS) can detect a choline resonance that is largely due to glycerophosphocholine. The authors tested the hypothesis that treatment with xanomeline, an M1 selective muscarinic cholinergic agonist, would be associated with a decrease in the 1H-MRS choline resonance.MethodPatients with mild to moderate Alzheimer’s disease received placebo or xanomeline for 6 months. 1H-MRS spectra were collected at baseline and after treatment discontinuation for 12 patients, two taking placebo and 10 taking xanomeline at a dose of 25 mg tid (N= 4), 50 mg tid (N= 3), or 75 mg tid (N= 3).ResultsFor the combined group of patients taking xanomeline, there was a significant decrease in the choline/creatine ratio from baseline to endpoint.ConclusionsTreatment of Alzheimer’s disease with a cholinergic agonist is associated with a decrease in the MRS choline resonance. Xanomeline may reduce breakdown of cholinergic neuron membranes by reducing the cellular requirement for free choline for acetylcholine synthesis.