Detection of presymptomatic Alzheimer's disease by fMRI

通过功能磁共振成像检测症状前阿尔茨海默病

• 批准号: 6574708
• 负责人: Charles Dennis Smith
• 金额: $ 31.84万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6574708
• 关键词: Alzheimer's disease; aging; bioimaging /biomedical imaging; biomarker; brain disorder diagnosis; clinical research; cognition; disease /disorder proneness /risk; female; functional magnetic resonance imaging; human middle age (35-64); human old age (65+); human subject; longitudinal human study; neural degeneration; neuropathology; neuropsychological tests; pathologic process; short term memory; statistics /biometry

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.

描述（由申请人提供）：阿尔茨海默氏病（AD）之前有一段时间，大脑功能发生可检测到的变化，而没有任何警告症状。这个时期可能是二十年或者更长。通过功能磁共振成像测量，正常女性在对抗命名过程中的激活程度会降低，而这些女性患迟发性阿尔茨海默病的风险增加，平均年龄仅为 53 岁。除了其他差异之外，这些人在记忆任务期间后扣带皮层的激活也减少了。我们的假设是，由于阿尔茨海默病的潜在病理学进展，命名、工作记忆和记忆方面的功能性 MRI 反应的改变将随着年龄的增长而明显恶化。在 AD 的早期、症状前阶段应用疾病缓解治疗可能会通过预防认知症状的出现产生深远的影响。目前正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 进展的生物标志物，功能磁共振成像可能会减少此类试验的持续时间和成本。该延续提案旨在检测高 AD 风险个体的大脑功能随时间的变化。我们将使用功能磁共振成像刺激任务来研究年龄范围为 40-65 岁和 65-90 岁的高和低 AD 风险受试者的正常教育匹配组，这些任务先前已证明高 AD 风险个体的区域差异。此外，我们将每隔五年重复之前在高和低 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。这些横断面和纵向研究的证据的汇集可以为阿尔茨海默病模型提供有力的证据，阿尔茨海默病是一种无情、缓慢进展的大脑病理学，在成年早期开始，但在晚期阶段产生临床症状之前一直得到补偿。