CEREBRAL BLOOD FLOW PATTERNS IN ALZHEIMER'S DISEASE

我们建议研究局部脑血流显像（rCBF）是否 会在大脑中产生与过去相同的异常模式 经氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）证实 阿尔茨海默型痴呆（ATD）患者的研究。 PET研究将 使用Donner 280晶体断层扫描仪和新的Donner 600晶体（2.5- 4 mm 分辨率）断层扫描仪，用15 O-H2O测量rCBF，15 O2用于氧 利用率和18F-FDG来测量代谢。 单光子发射 计算机断层扫描（SPECT）研究也将使用 修改了哈佛多检测器系统， 123 I-N-异丙基-p-碘苯丙胺（IMP）用于研究rCBF。 受试者将 根据严格的医学和神经心理学研究选择 标准，将包括家族性和散发性ATD。 由于许多 受试者将参与正在进行的使用PET的痴呆研究， 脑代谢，预测随访率高，磨损率低， 尸检的相关性很高 将通过比较以下物质的相对水平对数据进行定量分析： 活动在不同的大脑区域为每个病人和计算 rCBF率、局部脑葡萄糖代谢率（rCMRglu），以及 局部脑氧代谢率（rCMRO 2）。 它是假设 异常rCBF的模式将允许区分痴呆组。 此外，我们将分析数据，以检查rCBF之间的相关性， 和神经心理异常，并评估SPECT-IMP方法 与PET研究相比。 主要的假设是，在许多人身上看到的异常， 对ATD患者脑代谢的研究显示， rCBF异常。 SPECT研究将验证IMP作为 病理组织中的血流示踪剂，并评估这种降低的能力 成本成像模式来区分痴呆类型。 基本医疗 科学提案包括研究血流-代谢解耦 在早期阿尔茨海默病中，特别是在颞叶皮层。 而 我们相信血流-代谢偶联将被证明是大体上完整的 在这种疾病中，我们假设血流代谢的焦点区域 解偶联将使用高分辨率Donner 600 晶体断层扫描仪 这一发现将对我们的 了解阿尔茨海默病的发病机制，以及 制定治疗策略

We propose to study whether regional cerebral blood flow (rCBF) imaging will give the same pattern of abnormalities in the brain as has been demonstrated by fluorodeoxyglucose (FDG) positron emission tomography (PET) studies in patients with Alzheimer-type dementia (ATD). PET studies will use the Donner 280 crystal tomograph and a new Donner 600 crystal (2.5-4mm resolution) tomograph with 15O-H2O to measure rCBF, 15O2 for oxygen utilization and 18F-FDG to measure metabolism. Single photon emission computed tomography (SPECT) studies will also be performed using a modification of the Harvard multidetector system and 123I-N-isopropyl-p-iodoamphetamine (IMP) to study rCBF. Subjects will be selected according to rigorous medical and neuropsychological research criteria and will include both familial and sporadic ATD. Since many subjects will be part of ongoing demential research using PET to study brain metabolism, a high rate of follow-up with low attrition is predicted, and a high rate of autopsy correlation is likely. Data will be analyzed quantitatively by comparing relative levels of activity in different brain regions for each patient and by calculation of rates of rCBF, regional cerebral metabolic rates of gluocse (rCMRglu), and regional cerebral metabolic rates of O2 (rCMRO2). It is hypothesized that patterns of abnormal rCBF will allow differentiation of dementia groups. In addition, we will analyze the data to examine correlations between rCBF and neuropsychological abnormalities, and to evaluate the SPECT-IMP method in comparison to PET studies. The major hypothesis is that the abnormalities seen in numerous investigations of cerebral metabolism in ATD will show similar abnormalities in rCBF. The SPECT studies will validate the use of IMP as a flow tracer in pathological tissue, and evaluate the ability of this lower cost imaging modality to differentiate dementia types. A basic medical science proposal includes the investigation of a flow-metabolism decoupling in early Alzheimer's disease, particularly in the temporal cortex. While we believe that flow-metabolism coupling will be shown to be grossly intact in the disease, we hypothesize that focal regions of flow-metabolism uncoupling will be demonstrable using the high resolution Donner 600 crystal tomograph. This finding will be of great importance for our understanding of the pathogenesis of Alzheimer's disease, as well as for planning therapeutic strategies.