Nordberg A, Lundqvist H, Hartvig P, Andersson J, Johansson M, Hellstrŏm-Lindahi E, Långström B
Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Sweden.
Dement Geriatr Cogn Disord. 1997 Mar-Apr;8(2):78-84. doi: 10.1159/000106611.
Functional imaging techniques offer new possibilities for further understanding of changes in functional correlates of structural and biological changes in dementia disorders like Alzheimer's disease (AD). Regional disturbances in glucose metabolism and cerebral blood flow are known to occur in AD brains and probably roughly correlate to changes in neurotransmitter activities. A proper estimate would be to visualize the neuroreceptors themselves. In this study the cholinergic nicotinic and muscarinic receptors were studied in brain by positron emission tomography (PET). The rate constant k2* (s) (-)11C-nicotine was significantly higher (+43%) in temporal cortex of AD patients compared to controls (p < 0.017) indicating a lower binding of 11C-nicotine in AD brains compared to controls. Treatment with the cholinesterase inhibitor tacrine (80 mg daily) during 3 months to AD patients resulted in a mean plasma concentration of 7.7 +/- 0.8 ng/ml and a corresponding inhibition of the cholinesterase activity in plasma by 34 +/- 5%. A significantly lower k2* (increased binding) for 11C-nicotine binding (-15%; p < 0.006) was obtained in the temporal cortex after 3 months of treatment compared to prior treatment. The muscarinic antagonist 11C-benztropine was used to visualize muscarinic receptors and the binding capacity of 11C-benztropine (KR) was found to be decreased in the temporal cortex after 3 months of tacrine treatment.
功能成像技术为进一步理解痴呆症（如阿尔茨海默病，AD）中结构和生物学变化的功能关联变化提供了新的可能性。已知AD大脑中会出现葡萄糖代谢和脑血流量的局部紊乱，并且可能大致与神经递质活动的变化相关。更准确的评估是直接可视化神经受体本身。在本研究中，通过正电子发射断层扫描（PET）对大脑中的胆碱能烟碱受体和毒蕈碱受体进行了研究。与对照组相比，AD患者颞叶皮质中11C-尼古丁的速率常数k2*（s）（-）显著更高（+43%）（p < 0.017），这表明与对照组相比，AD大脑中11C-尼古丁的结合较低。给AD患者连续3个月每日服用胆碱酯酶抑制剂他克林（80毫克），导致平均血浆浓度为7.7 +/- 0.8纳克/毫升，血浆胆碱酯酶活性相应抑制34 +/- 5%。与治疗前相比，治疗3个月后颞叶皮质中11C-尼古丁结合的k2*显著降低（结合增加）（-15%；p < 0.006）。使用毒蕈碱拮抗剂11C-苯海索可视化毒蕈碱受体，发现他克林治疗3个月后颞叶皮质中11C-苯海索的结合能力（KR）降低。
