FUNCTIONAL MRI FOR EARLY DIAGNOSIS OF ALZHEIMER DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们先前的研究已经证明，遗传标记载脂蛋白E 4型等位基因(APOE-4)与阿尔茨海默病(AD)风险的增加相关。虽然各种神经心理和功能成像测试已被证明可以预测随后的认知能力下降，但此类研究不太可能很早就发现异常，因为它们：(1)评估“休息”状态下的大脑功能，此时精神活动控制不良，特定的心理过程未被激活；(2)通常包括没有后续认知衰退遗传风险的受试者；以及(3)强调仅对晚期疾病和实质性神经元丧失敏感的措施。在这里提出的研究中，我们的目标是研究认知激活任务中的功能磁共振成像(FMRI)，在一组具有阿尔茨海默病遗传风险的个体中。我们假设，在出现明显的神经心理衰退之前，神经元功能障碍的早期过程将导致代偿性认知策略，因此在那些后来将发展为更严重的功能丧失的个体中，神经元激活的模式将不同。我们预测，这种变化将在受AD影响最严重的大脑区域特别明显，包括顶后、内侧颞叶/海马区和额前区，此外，这些激活研究将比其他指标更早和更准确地预测认知功能下降，从而促进介入治疗的发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our previous research has demonstrated that the genetic marker, apolipoprotein E type 4 allele (APOE-4) is correlated with the increased risk of Alzheimer disease (AD). While a variety of neuropsychological and functional imaging tests have 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 earl y 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 most affected by AD, including posterior parietal, mesial temporal/hippocampal and pre-frontal 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.