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，大脑功能出现可检测到的变化，没有警告症状。这一时期可能是二十年或更长。在平均年龄只有53岁的晚发性阿尔茨海默病风险增加的正常女性的对峙命名过程中，功能磁共振成像测量的激活减少。这些人在记忆任务中，除了其他差异外，还减少了后扣带皮质的激活。我们的假设是，由于阿尔茨海默病的病理基础，命名、工作记忆和记忆方面的功能磁共振反应将随着年龄的增长而定量恶化。在阿尔茨海默病的这一早期症状前期应用的疾病修正治疗可以通过预防认知症状的出现而产生深远的影响。目前正在花费数百万美元进行大规模预防试验，以AD症状为终点。通过提供症状前AD进展的生物标记物，功能磁共振成像可能会减少此类试验的持续时间和成本。这一延续建议旨在检测AD高危个体随着时间的推移大脑功能的变化。我们将研究年龄在40-65岁和65-90岁之间的高和低AD风险受试者的正常教育匹配组，使用fMRI刺激任务，这些任务之前已经证明了高AD风险个体的地区差异。此外，我们将在五年后重复先前在高AD风险个体和低AD风险个体中进行的命名和流利性fMRI研究，以检测激活的纵向变化。这些横向和纵向研究的证据汇聚在一起，可能会为阿尔茨海默病的模型提供强有力的证据，这种模型是一种无情的、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.