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大脑结构，灌注和扩散张量MRI的“增值”，以预测未来的认知下降/阿尔茨海默氏病（AD）。在上一个赠款期间，我们招募并遵循了145名受试者在1.5T扫描的受试者，并以轻度的认知抱怨和障碍。我们发现，即使考虑了基线记忆功能，记忆下的下降也通过内嗅皮层体积，偏头扣金果白质的分数各向异性以及后扣带回回的灌注来明显预测。这些重要的新发现证实了我们的原始假设，并证明了DTI的价值，该价值在赠款资助后增加了。我们还开发了新的方法并在4 t进行了试点MRI研究，发现轻度认知障碍与特定海马子场的萎缩有关。扣带白质和后扣带灌注的扩散张量成像也提供了敏感的措施来检测早期AD。我们建议遵循已经在1.5 t招收的受试者，并研究240名新的非核心长者，并以纵向4T MRI的认知能力下降风险增加，包括：海马子场，扩散光谱成像（DSI）和灌注MRI的高分辨率测量。预测因子将在基线和12个月的MR中获得。在研究期间，每年评估的认知能力下降（与记忆函数基线的变化）。我们的主要假设是，在考虑了基线认知后，我们可以使用：CA 1-2过渡区的体积损失的组合（发现显示出MCI的显着变化），减少扣可质白蛋白的符号白蛋白小块和后覆盖凹入的组合。我们将测试所选变量集和结果之间的合并多个相关性。我们还将执行一系列结构化的探索，通过1）检查与主要假设和结果中未包含的相关性和其他预测因子，2）确定相关性：海马子场，帕拉希公共扣带的FA，parahampocal cingulum的FA，后膜后沿岩层cingulation usulation unitufuly and Memornormition，其他MRI测量，3）探索4），探索4）探索4）纵向成像的附加预测值。提出的项目之所以独特，是因为我们将使用：海马子场，扩散光谱成像和3D灌注MRI（占运输时间）以确定AD前驱阶段的病理生理学。该项目的其他重要性是，预测认知能力下降/痴呆症的最佳方法将改善对早期AD的检测，以及对治疗和预防试验的敏感结果指标，最终有助于治疗和预防AD。公共卫生相关性：阿尔茨海默氏病是一种毁灭性的疾病，没有有效的治疗，影响了超过400万美国人，由于人口老龄化而导致发病率迅速增长。一旦确定了治疗方法，必须确定那些不痴呆但有高风险的受试者患上未来阿尔茨海默氏病的风险，以便可以预防痴呆症。该应用程序使用MRI扫描来“预测无需老年人的认知下降”，并将导致识别有风险受试者的方法，然后将其进行预防治疗。