EMISSION COMPUTED TOMOGRAPHY OF LOCAL CEREBRAL FUNCTION

这个项目的目标是确定和纵向检查， 用正电子发射断层扫描， 与阿尔茨海默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 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确定。 对早期和晚期阿尔茨海默病、帕金森病、 疾病，伴或不伴痴呆，多发性梗塞性痴呆，和 对照将采取同样的措施， 在对两组患者进行的纵向研究中， 老年受试者处于痴呆发展的高风险，即， 孤立性记忆障碍的个体和特发性 帕金森病患者没有痴呆症。下列假设 将进行测试; 1）顶叶代谢和灌注下降是预测性的 阿尔茨海默氏病的个体与孤立的记忆障碍， 是特发性痴呆患者痴呆发作的预测指标 帕金森氏症。2)突触前胆碱能缺陷将区分 早期AD与其他孤立性记忆障碍的原因无关， 在帕金森病患者中区分那些注定要发展成 痴呆症，并会出现更早，更好地与认知相关 比顶叶低代谢下降。3)皮层毒蕈碱受体 在体内用PET测量的结合模式在早期 阿尔茨海默病和早期帕金森痴呆症，但不同的是， 事后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，以及 递质代谢我们将开发一种新的毒蕈碱受体（MAChR） 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 正电子发射体标记形式的制剂，在小动物中评价 然后在灵长类动物中，发展数学模型， 人体PET研究中的放射性示踪剂药代动力学。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，并提供新的见解 这些疾病的基本病理生理学。此类信息可 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.