FUNCTIONAL MRI FOR EARLY DIAGNOSIS OF ALZHEIMER DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们前期的研究表明，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）的风险增加相关。虽然各种神经心理学和功能成像测试已被证明可以预测随后的认知能力下降，但这些研究不太可能识别出非常早期的异常，因为它们：（1）在“休息”状态下评估大脑功能，此时精神活动控制不良，并且显示受损的特定精神过程未被激活;（2）通常包括没有随后下降遗传风险的受试者;最重要的是（3）强调仅对晚期疾病和大量神经元损失敏感的测量。在这里提出的研究中，我们的目标是研究功能性磁共振成像（fMRI）在认知激活任务中的一个队列的个人遗传风险的AD。我们假设，在出现明显的神经心理学衰退之前，神经元功能障碍的复杂过程将导致补偿性认知策略，使得神经元激活的模式在那些后来将发展为更严重的功能丧失的个体中会有所不同。我们预测，这种变化在受AD影响最大的脑区尤其明显，包括后顶叶、内侧颞叶/海马和前额区，此外，这些激活研究将比其他措施更早更准确地预测认知衰退，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.