PARIETAL AND ROLANDIC RCBF ACTIVATION IN DEMENTIA

痴呆症中顶叶和 ROLANDIC RBF 激活

• 批准号: 2049512
• 负责人: GEORG DEUTSCH
• 金额: $ 19.2万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2049512
• 关键词: Alzheimer's disease; association cortex; biomarker; blood flow measurement; brain disorder diagnosis; carbon dioxide; cerebrovascular disorder diagnosis; diagnosis design /evaluation; early diagnosis; human subject; longitudinal human study; neural information processing; neuropsychological tests; parietal lobe /cortex; performance; sensorimotor system; single photon emission computed tomography; temporal lobe /cortex; xenon

This project pursues three main aims through the study of resting and activated regional cerebral blood flow (rCBF) in early and late stage Alzheimer's Disease (AD). The research is based on findings concerning cerebral activity and responsivity in sensory-motor and association cortex in AD. (1) A proposed quantitative marker for early AD, based on the ratio of RCBF in posterior temporal-parietal to that in sensory motor cortex will be evaluated in a prospective study of 60 suspected early AD patients, the stage most difficult to diagnose clinically. (2) These patients will also be used in studies attempting to "capture" and investigate the period of increased cerebral response to mentally demanding tasks previously noted in a subgroup of well performing AD patients. This increased activity is hypothesized to reflect successful compensation to the degenerative processes accompanying early AD. The early AD patients will undergo successive studies of cortical flow under both simple sensory-motor tasks, aimed at preserved perirolandic cortex, and more complex cognitive tasks, aimed at association cortex. Based on previous data, approximately 75% of the patients screened are expected to become well defined AD cases, thus providing a substantial database on early changes in mild AD as well as permitting a retrospective assessment and refinement of the proposed RCBF marker. It is hypothesized that, as AD progresses, there is a curvilinear relationship between changes in performance and CBF related increases in association cortex and that decline of the activation response, following the period in which a peak occurs, signals the more debilitating stage of the disease. The end of effective compensation may mark the onset of more severe psychological and social problems as well as perhaps mark the end of a critical period during which AD is most responsive to therapeutic intervention. (3) A series of 30 moderately to severely impaired patients, recruited in prior years, will be followed into later stage AD to assess the effects of severe parenchymal degeneration on CO2 tests of vascular reactivity - especially in posterior association areas where vascular reserve appears unaffected in earlier stages of AD. This data is of potential diagnostic value in assessing dementia patients with questionable etiology. Late AD patients will also have RCBF studied during simple sensory-motor tasks to further evaluate the compensatory reactivity hypothesis in a situation where AD may be affecting rolandic cortex as well. Resting state RCBF will be measured with both 133Xe clearance and 99mTc HM-PAO SPECT. Task related activation will be assessed with 133Xe cortical flow studies. Combined, the aims offer theoretical information concerning performance changes and compensatory reactivity in degenerative dementia as well as data of clinical use in confirming early AD.

该项目通过研究休息和 早期和晚期激活的局部脑血流（rCBF） 阿尔茨海默病（AD）。 该研究基于以下方面的发现 感觉运动和联合皮层的大脑活动和反应性 在公元。 (1) 基于比率提出的早期 AD 量化标记 颞顶叶后部的 RCBF 与感觉运动皮层的 RCBF 的关系 在一项对 60 名疑似早期 AD 患者进行的前瞻性研究中进行评估， 临床上最难诊断的阶段。 (2)这些患者还会 用于试图“捕捉”和调查时期的研究 大脑对先前提到的高强度任务的反应增强 表现良好的 AD 患者亚组。 这种增加的活动是 假设反映了对退行性病变的成功补偿 伴随早期 AD 的过程。 早期AD患者将经历 在简单的感觉运动任务下皮质流的连续研究， 旨在保存兰周皮层和更复杂的认知任务， 针对联合皮层。 根据之前的数据，大约 75% 筛查的患者预计将成为明确的 AD 病例，因此 提供有关轻度 AD 早期变化的大量数据库以及 允许对拟议的 RCBF 进行回顾性评估和完善 标记。 据推测，随着 AD 的进展，存在一条曲线 性能变化与 CBF 相关增加之间的关系 关联皮层和激活反应的下降，如下 高峰出现的时期，标志着更虚弱的阶段 这种疾病。 有效补偿的结束可能标志着更多补偿的开始 严重的心理和社会问题，也可能标志着 AD 对治疗最敏感的关键时期 干涉。 (3) 一系列 30 名中度至重度受损的患者， 前几年招募的人员，将进入后期 AD 阶段进行评估 严重实质变性对血管CO2测试的影响 反应性 - 特别是在后部关联区域，血管 在 AD 的早期阶段，储备似乎不受影响。 这个数据是 评估痴呆患者的潜在诊断价值 病因学。 晚期 AD 患者还将在简单的过程中进行 RCBF 研究 感觉运动任务以进一步评估代偿反应性 AD 可能影响罗兰皮层的情况的假设 出色地。 静息状态 RCBF 将使用 133Xe 间隙和 99mTc HM-PAO 光谱。 任务相关的激活将使用 133Xe 进行评估 皮质流研究。 结合起来，这些目标提供了理论信息 关于退化中的性能变化和代偿反应性 痴呆症以及用于确认早期 AD 的临床使用数据。