EMISSION COMPUTED TOMOGRAPHY OF LOCAL CEREBRAL FUNCTION

这个项目的目标是识别和纵向检查， 通过正电子发射断层扫描，脑部最早的变化 与阿尔茨海默病发病相关的生理学 帕金森痴呆症。脑组织葡萄糖的PET测定 代谢、血流、M胆碱能受体密度，以及 突触前胆碱能标记物将在横断面上测定 帕金森氏症早、晚期阿尔茨海默病患者的研究 疾病，有无痴呆，多发性梗死性痴呆，以及 控制。将制定相同的措施，并与下列措施相匹配 两组儿童进行性认知功能衰退的纵向研究 患痴呆症的高危老年人，即， 孤立性记忆障碍和特发性记忆障碍的个体 帕金森氏症患者没有痴呆症。以下假设 1)顶叶新陈代谢和血流灌注下降是可预测的 阿尔茨海默氏病在患有孤立性记忆障碍和 可预测特发性痴呆患者的发病 帕金森氏症。2)突触前胆碱能缺陷将区分 早期AD由其他原因引起的孤立性记忆障碍，将 区分那些注定要发展的帕金森病患者 痴呆症，出现得更早，与认知能力有更好的相关性 比顶叶低代谢率下降。3)大脑皮层M受体 在体内测量的与PET的结合模式在早期类似 阿尔茨海默病和早期帕金森痴呆症，但不同于 验尸措施。为了实现这一目标，我们将开发和完善 几种新的PET技术，重点是测量 神经递质受体、突触前摄取系统和 递质代谢。我们将开发一种新的毒鼠强受体(MAChR) 配体、乙酰胆碱酯酶(AChE)配体和胆碱 乙酰转移酶(CAT)配体。开发过程包括 正电子发射体标记物的制备及其在小动物中的评价 然后在灵长类动物中，开发数学模型，并进行评估 放射性示踪剂在人体正电子发射计算机断层扫描研究中的药代动力学。这个项目应该 开发重要的新信息，预计将有助于早期 痴呆症的鉴别诊断和提供新的见解 这些疾病的基本病理生理学。这类信息可能 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.