Detection of presymptomatic Alzheimer's disease by fMRI

阿尔茨海默病(AD)之前有一段时间，大脑功能会发生明显的变化 没有任何征兆。这一时期可能是二十年或更长。激活由以下指标衡量 正常女性在命名过程中功能磁共振成像减少 平均年龄只有53岁的人患晚发性阿尔茨海默病的风险增加。这些是相同的 在记忆任务中，个体后扣带回皮质的激活减少。 其他方面的差距。我们的假设是，在命名、工作中改变的功能磁共振反应 记忆力和记忆力会随着年龄的增长而量化地恶化，这是由于渐进性潜在的 阿尔茨海默氏病的病理学。在这种早期、症状前期应用的疾病修正治疗 阿尔茨海默病的分期可以通过预防认知症状的发作产生深远的影响。数百万人 目前正在进行大规模预防试验，以阿尔茨海默病症状为终点。通过提供 作为有症状前AD进展的生物标志物，功能磁共振成像可能会减少持续时间和成本 这样的试验。这一延续建议旨在检测高AD风险时大脑功能的变化 随着时间的推移，个体。我们将研究与正常教育相匹配的AD高风险组和低AD组 年龄在40-65岁和65-90岁之间的受试者，使用之前已经过的fMRI刺激任务 在阿尔茨海默病高危人群中显示出地区差异。此外，我们将重复命名和 之前在高和低AD风险个体中进行的流畅性fMRI研究 五年来，为了检测激活的纵向变化。这些证据的汇聚 横断面和纵向研究可能为阿尔茨海默氏症模型提供强有力的证据 疾病是一种无情的、缓慢进展的大脑病理，始于成年早期，但至今仍 直到它在晚期出现临床症状。

Alzh¿imer'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 confi_ntation naming in normal women who have increased risk of late-onset Alzbeimer's disease, at an average age of only 53 years. These same individuals have reduced activation in the posterior cingulat¿ 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 Alzheimcr'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 ofpre-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.