Detection of presymptomatic Alzheimer's disease by fMRI

描述（由申请人提供）：阿尔茨海默病（AD）发生前有一段时间，可检测到大脑功能发生变化，但没有预警症状。这段时间可能是二十年或更长。在平均年龄仅为53岁的晚发性阿尔茨海默病风险增加的正常女性中，功能性磁共振成像测量的激活在对抗命名期间减少。在其他差异中，这些人在记忆任务中后扣带皮层的激活减少了。我们的假设是，由于阿尔茨海默病的病理进展，命名、工作记忆和记忆方面的功能性MRI反应的改变会随着年龄的增长而量化恶化。通过预防认知症状的发生，在阿尔茨海默病的早期症状前阶段应用疾病改善治疗可能会产生深远的影响。目前，以AD症状为终点的大规模预防试验花费了数百万美元。通过提供症状前AD进展的生物标志物，fMRI有可能减少此类试验的持续时间和成本。该方案旨在检测ad高危人群脑功能随时间的变化。我们将研究年龄在40-65岁和65-90岁之间的正常教育匹配的高、低ad风险受试者，使用fMRI刺激任务，这些任务之前已经证明了ad高风险个体的区域差异。此外，我们将在间隔5年后重复之前在高和低ad风险个体中进行的命名和流畅性fMRI研究，以检测激活的纵向变化。来自这些横断面和纵向研究的证据的集合可以为阿尔茨海默病模型提供强有力的证据，该模型是一种无情的、缓慢进展的大脑病理，始于成年早期，但在晚期出现临床症状之前一直处于补偿状态。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is preceded by a period when detectable changes in brain function occur without warning symptoms. This period may be twenty years or longer. Activation measured by functional magnetic resonance imaging is reduced during confrontation naming in normal women who have increased risk of late-onset Alzheimer's disease, at an average age of only 53 years. These same individuals have reduced activation in the posterior cingulate cortex during a memorization task, among other disparities. Our hypothesis is that the altered functional MRI responses in naming, working memory and memorization will quantifiably worsen with age, due to progressive underlying Alzheimer's disease pathology. Disease-modifying treatments applied in this early, pre-symptomatic stage of AD could have profound impact, by preventing the onset of cognitive symptoms. Millions are currently being spent on large-scale prevention trials, with AD symptoms as end-points. By providing a biomarker of pre-symptomatic AD progression, fMRI could potentially reduce the duration and costs of such trials. This continuation proposal is designed to detect changes in brain function in high-AD risk individuals over time. We will study normal education-matched groups of high- and low-AD risk subjects in the age ranges 40-65 and 65-90 years, using fMRI stimulus tasks which have previously demonstrated regional disparities in high-AD risk individuals. In addition, we will repeat the naming and fluency fMRI studies performed previously in high- and low-AD risk individuals after an interval of five years, in order to detect longitudinal changes in activation. The convergence of evidence from these cross-sectional and longitudinal studies could provide powerful evidence for a model of Alzheimer's disease as a relentless, slowly progressive brain pathology that begins early in adult life, but remains compensated until it produces clinical symptoms in its late stages.