FUNCTIONAL MRI FOR EARLY DIAGNOSIS OF ALZHEIMER DISEASE

用于阿尔茨海默病早期诊断的功能 MRI

• 批准号: 2055269
• 负责人: GARY William SMALL
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-10 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2055269
• 关键词: Alzheimer's disease; brain disorder diagnosis; brain electrical activity; brain imaging /visualization /scanning; cognition disorders; disease /disorder proneness /risk; early diagnosis; eye movements; family genetics; frontal lobe /cortex; genetic markers; hippocampus; human subject; longitudinal human study; magnetic resonance imaging; memory disorders; neural degeneration; neuropsychological tests; parietal lobe /cortex; performance; positron emission tomography; semantics; space perception; temporal lobe /cortex; visual stimulus

Our previous research demonstrated that the genetic marker, "apolipoprotein type 4 allele" (APOE-4) is correlated with the increased risk of Alzheimer's Disease (AD). While a variety of neuropsychological and functional imaging tests has been demonstrated to predict subsequent cognitive decline, such studies are unlikely to identify very early abnormalities because they: (1) assess brain function during a "resting" state when mental activity is poorly controlled and the specific mental processes showing impairment are not activated; (2) often include subjects without genetic risk for subsequent decline; and, most importantly (3) emphasize measures sensitive only to advanced disease and substantial neuronal loss. In the research proposed here, we aim to study functional Magnetic Resonance Imaging (fMRI) during cognitive activation tasks in a cohort of individuals genetically at-risk for AD. We hypothesize that, prior to the appearance of overt neuropsychological decline, the early processes of neuronal dysfunction will have resulted in compensatory cognitive strategies such that the pattern of neuronal activation will differ in those individuals who will later develop more severe functional losses. We predict that such changes will be particularly apparent in brain regions, and further, that these activation studies will predict cognitive decline earlier and more accurately than other measures, thereby facilitating the development of interventional therapies. As demonstrated in our preliminary data using fluoro-deoxyglucose PET(FDG-PET) as a crude marker of functional activation, we have shown clear evidence that activation studies can predict which individuals will suffer from the more rapid cognitive decline characteristic of AD. We have also developed a battery of neuropsychological tests sufficiently sensitive to changes in mental status that accurate indications of cognitive decline can be gathered in a two year period, thus making possible a longitudinal study of activation imaging. Our experience with fMRI has corroborated our expectation of improved sensitivity as compared to FDG-PET. We anticipate still further improvements in sensitivity as the new fMRI center becomes available at UCLA in Spring of 1995. This project will draw upon existing programs in Bran Mapping and early AD, an Alzheimer Disease Center (supported by the NIA), established multi-center collaborations in neurogenetics, and an available subject pool from 21 pedigrees with familial AD (410 living relatives [41 demented, 175 at- risk relatives, and 194 others]). The proposed activation studies of at- risk subjects also will elucidate pathophysiological mechanisms prior to confounding effects of disease chronicity. This research will provide the groundwork for future longitudinal studies using serial brain imaging that will determine the time course for progression of cerebral functional abnormalities, providing an objective and noninvasive means to monitor experimental therapeutic trials.

我们之前的研究表明，遗传标记， “载脂蛋白4型等位基因”（APOE-4）与 阿尔茨海默病（AD）的风险。 虽然各种神经心理学 和功能成像测试已经被证明可以预测随后的 认知能力下降，这样的研究不太可能很早就发现 异常，因为他们：（1）评估大脑功能在“休息” 当心理活动控制不良时， 显示损伤的过程没有被激活;（2）通常包括 受试者没有随后下降的遗传风险;并且，大多数 重要是（3）强调仅对晚期疾病敏感的措施， 严重的神经元缺失 在这里提出的研究中，我们的目标是 研究认知过程中的功能性磁共振成像（fMRI） 激活任务在一个群体的个人遗传风险的AD。 我们假设，在出现明显的神经心理症状之前， 下降，神经元功能障碍的早期过程将导致 在补偿性认知策略中， 激活将在那些个体中有所不同， 严重的功能丧失。 我们预测，这种变化将是 尤其是在大脑区域，而且，这些 激活研究将更早预测认知能力下降， 比其他措施准确，从而促进发展， 介入治疗 正如我们的初步数据所显示的那样， 氟脱氧葡萄糖PET（FDG-PET）作为功能性 激活，我们已经显示出明确的证据，激活研究可以 预测哪些人将遭受更快的认知 AD的衰退特征。 我们还开发了一种电池， 神经心理学测试对心理变化足够敏感， 可以收集认知能力下降准确指标的状态 为期两年，从而有可能进行纵向研究， 激活成像 我们在功能磁共振成像方面的经验证实了我们的 与FDG-PET相比，预期灵敏度提高。 我们 随着新的功能磁共振成像技术的发展， 中心于1995年春季在加州大学洛杉矶分校启用。 该项目将 利用现有的计划，在麸皮映射和早期AD，一个阿尔茨海默病 疾病中心（由NIA支持），建立多中心 神经遗传学的合作，以及21个可用的主题库 家族性AD家系（410名在世亲属[41名痴呆，175名at- （194人）。 拟议的at-激活研究 风险受试者也将阐明病理生理机制之前， 疾病慢性化的混杂效应。 这项研究将提供 未来使用连续脑成像进行纵向研究的基础 这将决定脑血管疾病进展的时间进程 功能异常，提供了一个客观和非侵入性的手段 来监控实验性的治疗试验