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: 2442307
• 负责人: GARY William SMALL
• 金额: $ 29.49万
• 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/2442307
• 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; functional magnetic resonance imaging; genetic markers; hippocampus; human subject; longitudinal human study; 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)与高脂血症相关 阿尔茨海默病(AD)的风险。而各种神经心理学 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 异常是因为它们：(1)评估“休息”期间的大脑功能 心理活动控制不佳时的状态和特定的心理状态 未激活显示损害的流程；(2)通常包括 没有遗传风险的后续衰退的受试者；以及，大多数 重要的是(3)强调只对晚期疾病敏感的措施和 大量神经元丢失。在这里提出的研究中，我们的目标是 认知过程中的功能磁共振成像研究 在一组具有阿尔茨海默病遗传风险的个体中的激活任务。 我们假设，在明显的神经心理症状出现之前 下降，会导致神经元功能障碍的早期过程 在代偿认知策略中，神经元的模式 那些稍后会发展成更多的人的激活情况会有所不同 严重的功能丧失。我们预测，这样的变化将是 在大脑区域尤其明显，而且，这些 激活研究将更早和更多地预测认知能力下降 比其他措施更准确，从而促进 介入治疗。如我们的初步数据所示，使用 氟脱氧葡萄糖正电子发射计算机断层扫描(FDG-PET)作为功能性疾病的粗略标志物 激活，我们已经展示了明确的证据，激活研究可以 预测哪些人会患上认知速度更快的 阿尔茨海默病的衰退特征。我们还开发了一种电池 神经心理测试对心理变化足够敏感 可以收集认知功能下降的准确迹象的状态 两年，从而使纵向研究成为可能 激活成像。我们的功能磁共振成像经验证实了我们的 与FDG-PET相比，期望提高灵敏度。我们 预计随着新的功能磁共振成像技术的推出，灵敏度将进一步提高 该中心将于1995年春天在加州大学洛杉矶分校投入使用。这个项目将 利用Bran map和早期AD中的现有程序，阿尔茨海默病 疾病中心(由NIA支持)，建立了多中心 神经遗传学方面的合作，以及21个可用的主题库 家族性阿尔茨海默病家系(410名在世亲属[41名精神病患者，175名阿尔茨海默病患者 风险亲属和其他194人])。拟开展的At-活化研究 风险受试者还将在发病前阐明病理生理机制。 疾病慢性病的混杂影响。这项研究将提供 为未来使用连续脑成像进行纵向研究奠定基础 这将决定大脑进展的时间进程 功能异常，提供了客观和非侵入性的手段 监督实验性的治疗试验。