CEREBRAL BLOOD FLOW PATTERNS IN ALZHEIMER'S DISEASE

该项目的上一个供资期间支持使用 正电子发射断层扫描(PET)与单光子发射 计算机断层扫描(SPECT)研究局部的变化 阿尔茨海默病(AD)的脑血流和代谢。 这个应用程序建议使用PET来研究 这些血流灌注异常之间的关系，认知 患者多巴胺代谢的缺陷和区域性变化 患有AD和帕金森氏病(PD)，这是一种与 一种具有临床、病理和影像特征的痴呆 AD的特征。而纹状体多巴胺缺乏症 帕金森病已经得到了很好的证实，来自PET和神经心理学的证据 调查还表明额叶是一个区域 受这种疾病的影响。阿尔茨海默病的临床和病理研究 提示多巴胺能功能障碍在病理生理学中的作用 额叶和锥体外系症状。的用法 高分辨率多巴胺代谢示踪剂(18F)-6-氟多巴 PET将允许确定额叶的作用， 壳核、尾状核多巴胺缺乏症的产生 这些患者的额叶低血流灌注和认知症状 疾病。 研究设计需要对帕金森病和AD患者进行评估，并 对照，特别提到额叶的存在 血流灌注异常、锥体外系症状和额叶 认知缺陷。所有患者都将从一个较大的 一项持续的纵向研究中登记的队列 使用SPECT进行血流检测，并将继续接受临床随访 以期进行最终的尸检关联。PET-600 所有人都将使用分辨率为2.6毫米的断层摄影仪 学习。紧接着一项评估区域血液的研究 使用示踪剂的流动(122I)-HIPDM(210秒半衰期)，受试者 将接受一项氟多巴PET研究。化学成分的定量分析 数据将利用通过动脉确定的输入函数 采用在线技术的导管和动态PET脑 摄取数据。血液和脑时间-活动曲线将被用来 与血液流动和多巴胺代谢模型相结合 推导出描述局部脑血流的参数和 多巴胺代谢。多巴胺代谢模型将使用 示踪剂重要代谢产物的已知时间进程 以便量化运输和新陈代谢的速率常数。 主要的假说是多巴胺的壳核异常 代谢将与锥体外系症状有关 PD和AD受试者。此外，额叶的血流灌注 缺陷和认知缺陷预计与 额叶多巴胺代谢减弱。这样的研究将 扩大我们对多巴胺特定模式的理解 这些状态的缺陷将与神经递质有关 认知和血流异常的缺陷 对理解病理生理学和生物力学的重要意义 这两种疾病的潜在治疗方法。

The previous funding period of this project supported the use of positron emission tomography (PET) and single photon emission computed tomography (SPECT) to study the changes in regional cerebral blood flow and metabolism in Alzheimer's disease (AD). This application proposes to use PET to investigate the relationship between these perfusion abnormalities, cognitive deficits, and regional changes in dopamine metabolism in patients with AD and Parkinson's disease (PD), an illness associated with a dementia sharing clinical, pathological, and imaging characteristics with AD. While the striatal dopamine deficiency in PD is well established, evidence from PET and neuropsychological investigations also implicates the frontal lobes as an area affected by the disease. In AD, clinical and pathologic studies suggest a role for dopaminergic dysfunction in the pathophysiology of frontal lobe and extrapyramidal symptoms. The use of the dopamine metabolic tracer (18F)-6-fluorodopa with high resolution PET will allow the determination of the role of frontal lobe, putaminal, and caudate dopamine deficiency in the production of frontal lobe hypoperfusion and cognitive symptomatology in these diseases. The study design entails the evaluation of PD and AD patients and controls, with specific reference to the presence of frontal lobe perfusion abnormalities, extrapyramidal symptoms, and frontal cognitive deficits. All patients will be selected from a larger cohort enrolled in an ongoing longitudinal study of changes in blood flow using SPECT, and will receive continued clinical follow up with a view to ultimate autopsy correlation. The PET-600 tomograph, which has a resolution of 2.6 mm, will be used for all studies. Immediately following a study to evaluate regional blood flow using the tracer (122I)-HIPDM (210 sec half life), subjects will undergo a fluorodopa PET study. Quantitative analysis of the data will utilize an input function determined via an arterial catheter with an on-line technique, together with dynamic PET brain uptake data. The blood and brain time-activity curves will be used in conjunction with models for blood flow and dopamine metabolism to derive parameters describing regional cerebral blood flow and dopamine metabolism. The dopamine metabolkc model will employ the known time course of significant metabolic products of the tracer in order to quantitate rate constants for transport and metabolism. The major hypothesis is that putaminal abnormalities of dopamine metabolism will be related to the extrapyramidal symptoms seen in PD and AD subjects. In addition, the frontal lobe perfusion deficits ans cognitive deficits are expected to be associated with diminished frontal lobe dopamine metabolism. Such studies will expand our understanding of the specific pattern of dopamine deficiency in these states and will relate neurotransmitter deficits to cognitive and blood flow abnormalities which have important implications for understanding the pathophysiology and potential treatments for both diseases.