EMISSION COMPUTED TOMOGRAPHY OF LOCAL CEREBRAL FUNCTION

描述：(改编自申请者的摘要)这项活动的目标 项目是用活体发射断层扫描来确定时间和 脑胆碱能酶活性下降的空间序列和 疑似早期阿尔茨海默病患者的胆碱能终末完整性S 疾病(AD)和帕金森S病(PD)，有无痴呆症，以及 将这些神经元生化改变与相关的 认知能力下降。需要检验的假设包括：1)在正常衰老中， AD和PD的模式不同，但胆碱能酶损失总是先于和 在严重程度和程度上超过胆碱能终末损失；2) 疑似早期AD的患者，胆碱能酶缺陷者将 进展为阿尔茨海默病和那些没有酶缺陷的人不会；3)患者 患有早期阿尔茨海默病，他们有最严重的颞叶胆碱能缺陷 枕骨低代谢也有死前的临床标准和 被认为是弥漫性路易体的神经心理特征 疾病(DLBD)。这些问题很难通过尸检来确定 由于早期疾病缺乏组织而进行的检查。发射 突触前核素标记的体层摄影研究 囊泡乙酰胆碱转运体(VAChT)和乙酰胆碱酯酶(AChE) 底物利用率被建议在特征良好的对照和 病人。在这些成像研究的同时，开发了一种新的 提出了乙酰胆碱酯酶抑制剂配体的概念。该代理将在小范围内进行评估 放射性示踪剂药代动力学制备的动物和灵长类动物研究 在人类身上的评估。这些努力的成功预计将有助于早期 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 促进患者的新药物分类，更好地匹配 患者接受治疗，更合理的途径获得新药，并指导 神经保护的新疗法和新策略。

DESCRIPTION: (Adapted from the applicant's abstract) The goals of this project are to determine, with in vivo emission tomography, the temporal and spatial sequence of declines in cerebral cholinergic enzyme activity and cholinergic terminal integrity in patients suspected of early Alzheimer s disease (AD) and in Parkinson s disease (PD), with and without dementia, and to correlate these neuronal biochemical alterations with associated cognitive declines. Hypotheses to be tested include: 1) in normal aging, AD, and PD, patterns differ, but cholinergic enzyme loss always precedes and exceeds cholinergic terminal loss both in severity and in extent; 2) in patients suspected of early AD, those with cholinergic enzyme deficits will progress to AD and those without enzyme deficits will not; and 3) patients with early AD who have the most severe temporal cholinergic deficits and occipital hypometabolism also have the premortem clinical criteria and neuro-psychological profile which have been attributed to Diffuse Lewy Body Disease (DLBD). These issues are difficult to establish with postmortem examinations due to the lack of tissue from early disease. Emission tomography studies using radioactive ligand markers of the presynaptic vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) substrate utilization are proposed in well characterized controls and patients. In parallel with these imaging studies, the development of a new AChE-inhibitor ligand is proposed. This agent will be evaluated in small animal and primate studies in preparation for radiotracer pharmacokinetic evaluation in humans. Success in these efforts 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 new pharmacologic classifications of patients, better matches of patients to therapies, more rational pathways to new drugs, and guides to new therapies and strategies for neuroprotection.