Volkow N D, Ding Y S, Fowler J S, Gatley S J
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Biol Psychiatry. 2001 Feb 1;49(3):211-20. doi: 10.1016/s0006-3223(00)01112-4.
One of the strategies in the treatment of Alzheimer's disease is the use of drugs that enhance cholinergic brain function, since it is believed that cholinergic dysfunction is one of the factors that contributes to cognitive deterioration. Positron emission tomography is a medical imaging method that can be used to measure the concentration, kinetics, and distribution of cholinergic-enhancing drugs directly in the human brain and assess the effects of the drugs at markers of cholinergic cell viability (vesicular transporters, acetylcholinesterase), at muscarininc and nicotinic receptors, at extracellular acetylcholine, at markers of brain function (glucose metabolism and blood flow), and on amyloid plaque burden in vivo in the brains of patients with Alzheimer's disease. In addition, these measures can be applied to assess the drugs' pharmacokinetic and pharmacodynamic properties in the human brain. Since the studies are done in living human subjects, positron emission tomography can evaluate the relationship between the drugs' biological, behavioral, and cognitive effects; monitor changes in brain function in response to chronic treatment; and determine if pharmacologic interventions are neuroprotective. Moreover, because positron emission tomography has the potential to identify Alzheimer's disease during early disease, it can be used to establish whether early interventions can prevent or delay further development.
治疗阿尔茨海默病的策略之一是使用增强胆碱能脑功能的药物，因为人们认为胆碱能功能障碍是导致认知衰退的因素之一。正电子发射断层扫描是一种医学成像方法，可用于直接在人脑中测量增强胆碱能药物的浓度、动力学和分布，并在体内评估药物对胆碱能细胞活力标志物（囊泡转运体、乙酰胆碱酯酶）、毒蕈碱和烟碱受体、细胞外乙酰胆碱、脑功能标志物（葡萄糖代谢和血流）以及阿尔茨海默病患者大脑中淀粉样斑块负荷的影响。此外，这些测量可用于评估药物在人脑中的药代动力学和药效学特性。由于这些研究是在活体人类受试者中进行的，正电子发射断层扫描可以评估药物的生物学、行为和认知效应之间的关系；监测长期治疗后脑功能的变化；并确定药物干预是否具有神经保护作用。此外，由于正电子发射断层扫描有可能在疾病早期识别阿尔茨海默病，它可用于确定早期干预是否能够预防或延缓疾病的进一步发展。
