EMISSION COMPUTED TOMOGRAPHY OF LOCAL CEREBRAL FUNCTION

该项目的目标是纵向识别和检查， 通过正电子发射断层扫描，大脑中最早的改变 与阿尔茨海默氏病发病相关的生理学 帕金森痴呆症。 PET 测定脑葡萄糖的测量值 新陈代谢、血流量、毒蕈碱胆碱能受体密度，以及 突触前胆碱能标记物将在横截面中测定 对早期和晚期阿尔茨海默病、帕金森病患者的研究 疾病，伴或不伴痴呆、多发性梗塞性痴呆，以及 控制。将采取相同的措施并与以下措施相匹配 两组纵向研究中进行性认知衰退 患有痴呆症的高风险老年受试者，即 患有孤立性记忆障碍的人和患有特发性记忆障碍的人 没有痴呆的帕金森病患者。以下假设 将接受测试； 1) 壁代谢和灌注下降是可预测的 患有孤立性记忆障碍的阿尔茨海默病和 可以预测特发性痴呆症患者的痴呆发作 帕金森病。 2）突触前胆碱能缺陷将区分 由其他原因引起的孤立性记忆障碍的早期 AD，将 区分那些注定会患帕金森病的患者 痴呆症，并且会出现得更早，并且与认知能力更好地相关 比顶叶代谢减退下降。 3) 皮质毒蕈碱受体 PET 体内测量的结合模式在早期是相似的。 阿尔茨海默病和早期帕金森痴呆症，但不同 尸检措施。为了实现这一目标，我们将开发和完善 几种新的 PET 技术专注于测量 神经递质受体、突触前摄取系统和酶 递质代谢。我们将开发一种新的毒蕈碱受体（MAChR） 配体和乙酰胆碱酯酶（AChE）配体和胆碱 乙酰转移酶（CAT）配体。开发流程包括 正电子发射体标记形式的制备，小动物评价 然后在灵长类动物中，数学模型的开发和评估 人体 PET 研究中放射性示踪剂药代动力学的研究。这个项目应该 开发重要的新信息，预计将有助于早期 痴呆症的鉴别诊断并提供新的见解 深入了解这些疾病的基本病理生理学。此类信息可以 促进引入已知的治疗策略。

The goal of this project is to identify and to examine longitudinally, with positron emission tomography, the earliest alterations in cerebral physiology associated with the onsets of Alzheimer's disease and of parkinsonian dementia. PET determined measures of cerebral glucose metabolism, blood flow, muscarinic cholinergic receptor densities, and presynaptic cholinergic markers will be determined in cross-sectional studies of patients with early and late Alzheimer's disease, Parkinson's disease, with and without dementia, multiple infarct dementia, and controls. The same measures will be made and matched against measures of progressive cognitive decline in longitudinal studies of two groups of elderly subjects at high risk for the development of dementia, i.e., individuals with isolated memory impairment, and those with idiopathic Parkinson's disease who do not have dementia. The following hypotheses will be tested; 1) Parietal metabolic and perfusion decline is predictive of Alzheimer's disease in individuals with isolated memory impairment and is predictive of the onset of dementia in patients with idiopathic Parkinson's disease. 2) Presynaptic cholinergic deficits will distinguish early AD from other causes of isolated memory impairment, will distinguish among parkinsonian patients those destined to develop dementia, and will appear earlier and correlate better with cognitive decline than parietal hypo-metabolism. 3) Cortical muscarinic receptor binding patterns measured in vivo with PET are similar in early Alzheimer's disease and early parkinsonian dementia, but differ from post-mortem measures. To accomplish this, we will develop and refine several new PET techniques which are focused on measurement of neurotransmitter receptors, presynaptic uptake systems, and enzymes of transmitter metabolism. We will develop a new muscarinic receptor (MAChR) ligand, and acetylchol-inesterase (AChE) ligand, and a choline acetyltransferase (CAT) ligand. The development process includes preparation in positron emitter labeled form, evaluation in small animals and then in primates, development of mathematical models, and assessment of radiotracer pharmacokinetics in human PET studies. This project should develop important new information which is expected to aid the early differential diagnosis of dementing disorders and to provide new insights into the basic pathophysiology of these diseases. Such information could facilitate the introduction of knew treatment strategies.