Prediction of cognitive decline with structural, diffusion, and perfusion MRI

通过结构、扩散和灌注 MRI 预测认知能力下降

• 批准号: 8034207
• 负责人: MICHAEL W WEINER
• 金额: $ 85.54万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034207
• 关键词: Accounting; Affect; Aging; Alzheimer' s Disease; American; Anisotropy; Atrophic; Axon; Basal Ganglia; Biological Models; Blood flow; Brain; Brain region; Cerebellum; Cerebrovascular Circulation; Cessation of life; Clinical; Cognition; Cognitive; Core-Binding Factor; Cox Proportional Hazards Models; Critiques; Data; Deafferentation procedure; Dementia; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Elderly; Enrollment; Event; Functional disorder; Funding; Future; Goals; Grant; Health; Hippocampus (Brain); Image; Image Analysis; Impaired cognition; Impairment; Incidence; Individual; Lateral; Lead; Linear Regressions; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Memory; Methods; Modeling; Motor Cortex; Nerve Degeneration; Neurons; Outcome; Outcome Measure; Pathology; Patients; Pattern; Perfusion; Phase; Population; Predictive Value; Prevention; Preventive; Procedures; Process; Recruitment Activity; Resolution; Risk; Scanning; Series; Specific qualifier value; Specificity; Spin Labels; Staging; Statistical Methods; Structure; Survival Analysis; Symptoms; System; Temporal Lobe; Testing; Thick; Time; Weight; abeta accumulation; base; cingulate gyrus; cohort; effective therapy; entorhinal cortex; executive function; frontal lobe; high risk; improved; interest; mild neurocognitive impairment; prevent; research clinical testing; response; tau Proteins; technology development; white matter

DESCRIPTION (provided by applicant): Our goal is to determine the "value added" of regional and longitudinal brain structural, perfusion, and diffusion tensor MRI, to predict future cognitive decline/Alzheimer's disease (AD). During the previous grant period we recruited and followed longitudinally 145 subjects scanned at 1.5T with mild cognitive complaints and impairments. We found that even after accounting for baseline memory function, memory decline was significantly predicted by entorhinal cortex volume, fractional anisotropy of the parahippocampal cingulum white matter, and perfusion of the posterior cingulate gyrus. These important new findings confirmed our original a priori hypothesis, and also demonstrated the value of DTI which was added on after the grant was funded. We also developed new methods and performed pilot MRI studies at 4 T and found that mild cognitive impairment is associated with atrophy of specific hippocampal subfields. Diffusion tensor imaging of cingulum white matter and perfusion of posterior cingulate also provide sensitive measures to detect early AD. We propose to follow subjects already enrolled at 1.5 T and also study 240 new nondemented elders at increased risk for cognitive decline with longitudinal 4T MRI including: high-resolution measurements of hippocampal subfields, diffusion spectral imaging (DSI) and perfusion MRI. Predictors will be obtained from MR at baseline and 12 months. Outcomes will be cognitive decline (change from baseline of memory function) assessed annually for the duration of the study. Our primary hypothesis is that after baseline cognition is accounted for, we can predict decline of memory function using a combination of: volume loss in CA 1-2 transition zone (a hippocampal subfield found to show significant changes in MCI), reduced fractional anisotropy of the cingulum white matter tract, and posterior cingulate perfusion. We will test whether the combined multiple correlations between the selected set of variables and the outcome are significant. We will also perform a series of structured explorations to test our biological model by 1) examining correlations and other predictors not included in the primary hypotheses and outcomes, 2) determining correlations between: hippocampal subfields, FA of parahippocampal cingulum, posterior cingulate perfusion, other MRI measures and memory, 3) exploring the prediction of imaging for decline of non-memory cognition, 4) exploring the added predictive value of longitudinal imaging. The proposed project is unique because we will use: quantification of hippocampal subfields, diffusion spectrum imaging and 3D perfusion MRI (accounting for transit time) to determine the pathophysiology of the prodromal stages of AD. Additional significance of this project is that optimum methods to predict cognitive decline/dementia will lead to improved detection of early AD, and sensitive outcome measures for treatment and prevention trials, helping ultimately to treat and prevent AD. PUBLIC HEALTH RELEVANCE: Alzheimer's disease is a devastating illness with no effective treatment, affecting more than four million Americans, with a rapidly growing incidence due to aging of the population. Once a treatment is identified, it will be important to identify subjects who are not demented but who are at high risk for developing future Alzheimer's disease, so that the dementia can be prevented. This application uses MRI scanning to "predict cognitive decline" in nondemented elders and will lead to methods which identify subjects at risk, who can then be put on preventive treatment once it's available.

描述（由申请人提供）：我们的目标是确定区域和纵向脑结构、灌注和扩散张量 MRI 的“附加值”，以预测未来的认知能力下降/阿尔茨海默病 (AD)。在上一个资助期间，我们招募并纵向跟踪了 145 名受试者，这些受试者以 1.5T 扫描，患有轻度认知障碍和障碍。我们发现，即使在考虑了基线记忆功能后，内嗅皮层体积、海马旁扣带回白质的分数各向异性和后扣带回的灌注也可以显着预测记忆衰退。这些重要的新发现证实了我们最初的先验假设，也证明了在拨款资助后添加的 DTI 的价值。我们还开发了新方法并在 4 T 下进行了初步 MRI 研究，发现轻度认知障碍与特定海马亚区的萎缩有关。扣带回白质的弥散张量成像和后扣带回的灌注也为检测早期 AD 提供了敏感的措施。我们建议跟踪已在 1.5 T 入组的受试者，并利用纵向 4T MRI 来研究 240 名认知能力下降风险增加的新非痴呆老年人，包括：海马亚区的高分辨率测量、扩散光谱成像 (DSI) 和灌注 MRI。预测因子将从基线和 12 个月时的 MR 中获得。结果将是在研究期间每年评估的认知衰退（记忆功能基线的变化）。我们的主要假设是，考虑到基线认知后，我们可以通过以下组合来预测记忆功能的下降：CA 1-2 过渡区的体积损失（发现 MCI 发生显着变化的海马亚区）、记忆功能各向异性分数的降低扣带回白质束和后扣带回灌注。我们将测试所选变量集与结果之间的组合多重相关性是否显着。我们还将进行一系列结构化探索来测试我们的生物模型，方法是：1）检查主要假设和结果中未包含的相关性和其他预测因素，2）确定以下之间的相关性：海马亚区、海马旁扣带回 FA、后扣带回灌注、其他MRI 测量和记忆，3）探索成像对非记忆认知衰退的预测，4）探索纵向成像的附加预测价值。拟议的项目是独一无二的，因为我们将使用：海马亚区的量化、扩散谱成像和 3D 灌注 MRI（考虑传输时间）来确定 AD 前驱阶段的病理生理学。该项目的另一个重要意义在于，预测认知能力下降/痴呆的最佳方法将改善早期 AD 的检测，以及治疗和预防试验的敏感结果测量，最终帮助治疗和预防 AD。公共健康相关性：阿尔茨海默病是一种毁灭性的疾病，没有有效的治疗方法，影响着超过四百万美国人，由于人口老龄化，发病率迅速上升。一旦确定了治疗方法，重要的是要确定哪些受试者没有痴呆，但未来患阿尔茨海默病的风险很高，这样就可以预防痴呆症。该应用程序使用核磁共振扫描来“预测非痴呆老年人的认知能力下降”，并将产生识别有风险的受试者的方法，一旦有预防性治疗，就可以对这些受试者进行预防性治疗。