Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimers disease
Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimers disease
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DOI：
10.1093/brain/awn326
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发表时间：
2009-02-01
期刊：
影响因子：
14.5
通讯作者：
Eidelberg, David
中科院分区：
文献类型：
--
作者：
Smith, Gwenn S.;Kramer, Elisse;Eidelberg, David
临床前和人类神经药理学证据表明，胆碱能调节单胺类物质是阿尔茨海默病的一种病理生理和治疗机制。本研究测量了胆碱酯酶抑制剂和烟碱受体调节剂加兰他明治疗对选择性5-羟色胺再摄取抑制剂西酞普兰的大脑代谢反应的影响。7名可能患有阿尔茨海默病的患者和7名人口学上相似的对照组在注射生理盐水安慰剂(第1天)和西酞普兰(40 mg，静脉注射，第2天)后进行了两次正电子发射断层扫描(PET)葡萄糖代谢扫描。阿尔茨海默病患者在滴定到24毫克加兰他明剂量后2个月重复扫描方案。在基线时，阿尔茨海默病患者的大脑葡萄糖代谢在右侧颞叶中段、左侧后扣带回和顶叶皮质(楔前叶和顶下小叶)与对照组相比降低，这与预期不谋而合。在阿尔茨海默病患者中，两组患者在西酞普兰治疗后都表现出大脑葡萄糖代谢的急剧下降，程度更大。在患者中，与对照组相比，西酞普兰在治疗前更大程度地降低了双侧额中回、左侧颞中回和右侧扣带后回的糖代谢。加兰他明单独治疗可增加右侧楔前叶、右侧顶下小叶和右侧枕中回的新陈代谢。相比之下，在加兰他明治疗期间，西酞普兰增加了右侧额中回、右侧中央后回、右侧颞上中回和右侧小脑的代谢。与临床前数据一致的是，加兰他明和西酞普兰的联合脑代谢效应表明，胆碱能系统和5-羟色胺能系统之间存在协同作用。
Pre-clinical and human neuropharmacological evidence suggests a role of cholinergic modulation of monoamines as a pathophysiological and therapeutic mechanism in Alzheimers disease. The present study measured the effects of treatment with the cholinesterase inhibitor and nicotinic receptor modulator, galantamine, on the cerebral metabolic response to the selective serotonin reuptake inhibitor, citalopram. Seven probable Alzheimers disease patients and seven demographically comparable controls underwent two positron emission tomography (PET) glucose metabolism scans, after administration of a saline placebo infusion (Day 1) and after citalopram (40 mg, IV, Day 2). The scan protocol was repeated in the Alzheimers disease patients 2 months after titration to a 24 mg galantamine dose. At baseline, cerebral glucose metabolism was reduced in Alzheimers disease patients relative to controls in right middle temporal, left posterior cingulate and parietal cortices (precuneus and inferior parietal lobule), as expected. Both groups demonstrated acute decreases in cerebral glucose metabolism after citalopram to a greater extent in the Alzheimers disease patients. In the patients, relative to the controls, citalopram decreased glucose metabolism to a greater extent in middle frontal gyrus (bilaterally), left middle temporal gyrus and right posterior cingulate prior to treatment. Galantamine treatment alone increased metabolism in the right precuneus, right inferior parietal lobule and right middle occipital gyrus. In contrast, during galantamine treatment, citalopram increased metabolism in the right middle frontal gyrus, right post-central gyrus, right superior and middle temporal gyrus and right cerebellum. The combined cerebral metabolic effects of galantamine and citalopram suggest, consistent with preclinical data, a synergistic interaction of cholinergic and serotonergic systems.