Detection of presymptomatic Alzheimer's disease by fMRI

描述（由申请人提供）：阿尔茨海默病（AD）之前有一段时间，此时脑功能发生可检测到的变化，但没有警告症状。这一时期可以是二十年或更长。通过功能磁共振成像测量的激活在正常女性中的对抗命名过程中减少，这些女性患晚发性阿尔茨海默病的风险增加，平均年龄仅为53岁。这些人在记忆任务中后扣带皮层的激活减少，以及其他差异。我们的假设是，命名，工作记忆和记忆的功能性MRI反应的改变将量化恶化随着年龄的增长，由于渐进的潜在阿尔茨海默病的病理。在AD的早期症状前阶段应用疾病改善治疗可以通过预防认知症状的发作而产生深远的影响。目前，数百万美元用于大规模预防试验，以AD症状为终点。通过提供症状前AD进展的生物标志物，fMRI可能会减少此类试验的持续时间和成本。这项延续性建议旨在检测高AD风险个体随着时间的推移大脑功能的变化。我们将研究正常教育匹配组的高和低AD风险的受试者在40-65和65-90岁，使用功能磁共振成像刺激任务，以前已经证明了区域差异的高AD风险的个人。此外，我们将重复命名和流畅性功能磁共振成像研究之前进行的高和低AD风险的个人间隔五年后，为了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融合可以为阿尔茨海默病的模型提供强有力的证据，阿尔茨海默病是一种无情的，缓慢进行的大脑病理学，在成年早期开始，但直到它在晚期产生临床症状才得到补偿。

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.