Nordberg A, Lilja A, Lundqvist H, Hartvig P, Amberla K, Viitanen M, Warpman U, Johansson M, Hellström-Lindahl E, Bjurling P
Department of Pharmacology, Uppsala University, Sweden.
Neurobiol Aging. 1992 Nov-Dec;13(6):747-58. doi: 10.1016/0197-4580(92)90099-j.
Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [18F]-fluoro-deoxy-glucose (18F-FDG) (tracer for glucose metabolism); 11C-butanol (cerebral blood flow) and (S)(-)- and (R)(+)-[N-11C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of 11C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(-)- and (R)(+)11C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(-)11C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.
三名阿尔茨海默病患者，一名68岁患有轻度痴呆的女性和两名患有中度痴呆的男性（分别为64岁和72岁），口服胆碱酯酶抑制剂他克林（四氢氨基吖啶），每日80毫克，持续数月。在治疗前、治疗3周和3个月后，使用正电子发射断层扫描（PET）对患者进行检查。PET研究涉及一个多示踪剂系统，该系统由[18F] - 氟脱氧葡萄糖（18F - FDG）（葡萄糖代谢示踪剂）、11C - 丁醇（脑血流量）以及（S）（ - ） - 和（R）（ + ） - [N - 11C - 甲基] - 尼古丁（烟碱受体；胆碱能神经活动）组成。他克林治疗增加了大脑对11C - 尼古丁的摄取。在所有三名患者接受他克林治疗后，在额叶和颞叶皮质观察到两种对映体（S）（ - ） - 和（R）（ + ） - 11C - 尼古丁摄取的显著差异减小。动力学分析表明，（S）（ - ） - 11C - 尼古丁在大脑中的结合增加，这与烟碱胆碱能受体的恢复相符。在轻度痴呆患者接受3周和3个月治疗后观察到最明显的效果。在用他克林治疗3个月时，68岁患有轻度痴呆的患者脑葡萄糖利用率增加，64岁患有中度痴呆的男性也略有增加。他克林给药不影响脑血流量。他克林治疗3周后获得的PET数据与神经心理表现的改善平行。这项研究通过PET在体内显示了他克林治疗对阿尔茨海默病患者大脑诱导的神经化学效应。在疾病早期用他克林进行干预可能对临床改善是必要的。
