Changes in brain 11C-nicotine binding sites in patients with mild Alzheimer's disease following rivastigmine treatment as assessed by PET
Changes in brain 11C-nicotine binding sites in patients with mild Alzheimer's disease following rivastigmine treatment as assessed by PET
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DOI：
10.1007/s00213-007-0725-z
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发表时间：
2007-05-01
影响因子：
3.4
通讯作者：
Nordberg, Agneta
中科院分区：
文献类型：
--
作者：
Kadir, Ahmadul;Darreh-Shori, Taher;Nordberg, Agneta
基本原理 在阿尔茨海默病 (AD) 患者的大脑中观察到皮质烟碱乙酰胆碱受体显着减少。尽管胆碱酯酶抑制剂用于轻度至中度 AD 患者的对症治疗，但大量长期治疗研究表明，它们可能通过恢复中枢胆碱能神经传递来稳定或阻止疾病的进展。因此，我们使用正电子发射断层扫描（PET）技术作为一种灵敏的方法来评估AD患者大脑中尼古丁结合位点的纵向变化。 目的 评估卡巴拉汀治疗后脑部烟碱结合位点的变化与脑脊液（CSF）和血浆中胆碱酯酶抑制水平的关系以及患者在不同神经心理测试中认知能力的变化。 材料与方法 10名轻度AD患者接受了卡巴拉汀治疗。卡巴拉汀 12 个月。使用给予 O-15-水和 (S)(-)C-11-尼古丁的双示踪剂 PET 模型来评估基线时以及治疗 3 个月和 12 个月后大脑中的 C-11-尼古丁结合位点。采用比色法评估脑脊液和血浆中的胆碱酯酶活性。结果与基线相比，治疗3个月后，几个皮质脑区域的11C-尼古丁结合位点显着增加12-19%，而治疗12个月后增加不显着。治疗 3 个月后，脑脊液和血浆中较低的酶抑制与较高的皮质 C-11-尼古丁结合相关。在12个月的随访中，C-11-尼古丁结合与注意力任务呈正相关。结论 卡巴拉汀治疗期间C-11-尼古丁结合的变化可能代表胆碱能和相关神经元网络的重塑。
Rationale Marked reduction in the cortical nicotinic acetylcholine receptors is observed in the brain of patients suffering from Alzheimer's disease (AD). Although cholinesterase inhibitors are used for symptomatic treatment of mild to moderate AD patients, numerous long-term treatment studies indicate that they might stabilize or halt the progression of the disease by restoring the central cholinergic neurotransmission. Thus, we used positron emission tomography (PET) technique as a sensitive approach to assess longitudinal changes in the nicotine binding sites in the brains of patients with AD.Objectives To evaluate changes in brain nicotinic binding sites in relation to inhibition level of cholinesterases in cerebrospinal fluid (CSF) and plasma and changes in cognitive performance of the patients in different neuropsychological tests after rivastigmine treatment.Materials and methods Ten mild AD patients received rivastigmine for 12 months. A dual-tracer PET model with administration of O-15-water and (S)(-)C-11-nicotine was used to assess C-11-nicotine binding sites in the brain at baseline and after 3 and 12 months of the treatment. Cholinesterase activities in CSF and plasma were assessed colorimetrically.Results The 11C-nicotine binding sites were significantly increased 12-19% in several cortical brain regions after 3 months compared with baseline, while the increase was not significant after 12 months of the treatment. After 3 months treatment, low enzyme inhibition in CSF and plasma was correlated with higher cortical C-11-nicotine binding. The C-11-nicotine binding positively correlated with attentional task at the 12-month follow-up.Conclusions Changes in the C-11-nicotine binding during rivastigmine treatment might represent remodeling of the cholinergic and related neuronal network.