Post-mortem MRI for improving the diagnosis of Alzheimer’s mimics in the oldest old

尸检 MRI 可改善老年痴呆症的诊断

基本信息

批准号：
10663783
负责人：
Seyed Ahmad Sajjadi
金额：
$ 19.83万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10663783
关键词：
3-Dimensional Age Aged, 80 and over Aging Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Area Atrophic Autopsy Biological Markers Brain California Characteristics Custom Data Dementia Detection Development Diagnosis Disease Goals Grant Hemorrhage Hippocampus Image Individual Lacunar Infarctions Lesion Life Location Longitudinal, observational study MRI Scans Magnetic Resonance Imaging Motion Participant Pathology Persons Pharmaceutical Preparations Population Prevalence Prospective Studies Public Health Research Resolution Sample Size Sampling Scanning Series Signal Transduction Slide Testing Therapeutic Time Translations Universities Work age group aged brain abnormalities brain magnetic resonance imaging brain research brain tissue cerebral microinfarct cohort detection sensitivity hippocampal sclerosis improved in vivo insight interest magnetic resonance imaging biomarker multimodality neuropathology prisma sample fixation targeted treatment therapy development tool

项目摘要

The oldest old, people aged 90 years or older, are the fastest growing segment of the worldwide population with a staggering increase in the prevalence of dementia. Unlike younger groups, Alzheimer’s disease neuropathology (ADNP) is no longer the most dominant degenerative neuropathology in the oldest old and dementia is often due to the presence of multiple neuropathologies. Hippocampal sclerosis (HS) and small vessel lesions (SVL) are important contributors to dementia in the oldest old. Due to lack of reliable biomarkers, HS remains undetected and SVLs are under-recognized during life. These limitations hamper efforts in developing target-specific therapeutics. The long-term goal of this project is to improve the in vivo diagnosis of these important pathologies using insights gained from postmortem brain MRI. Compared with MRIs acquired during life, postmortem MRI has the ability to acquire significantly higher quality scans allowing for better quantification and localization of abnormalities of brain tissue. The 90+ Study, a longitudinal observational study of participants aged 90 years or older at the University of California, Irvine, provides a unique opportunity to examine the utility of postmortem brain MRI in the oldest old. Neuropathological assessments are currently being conducted on the donated brains and a considerable subset of participants will have undergone brain MRI during life allowing for comparisons between in vivo and postmortem imaging findings and translation of the insights gained from postmortem to in vivo MRIs. We have already developed the sequences and started acquisition of postmortem MRI scans proving the feasibility of our approach. We anticipate acquiring postmortem MRI scans for 50 participants and based on our current data, this sample will provide sufficient number of cases harboring the two pathologies of interest i.e. HS and SVLs. Moreover, our power calculations indicate that we will be able to test the hypotheses of this proposal with this sample size. In aim 1, we will test the hypothesis that hippocampal sclerosis will be associated with MRI detectable volume loss and signal change in the hippocampus and that postmortem MRI has a higher sensitivity to detect these compared with MRI acquired during life. In aim 2, we will test the hypothesis that postmortem MRI allows for detection of higher numbers of SVLs when compared with MRI acquired during life. At completion of this work and utilizing the insights gained from this study, we will apply for an R01 grant to prospectively study the utility of post-mortem MRI in prediction of hippocampal sclerosis and SVLs in a large cohort. The insights gained from these studies will be used to enable prediction of HS and improve the detection of SVLs in MRIs acquired during life. This will subsequently enable development of targeted therapies against these two important pathologies that significantly contribute to development of dementia in fastest growing segment of our population that will represent half of all of those suffering from dementia by 2050.

最年长的老年人，即 90 岁或以上的老年人，是全球人口增长最快的群体与年轻群体不同，阿尔茨海默病的患病率急剧上升。神经病理学（ADNP）不再是最古老和最古老的退行性神经病理学痴呆通常是由多种神经病变引起的。由于缺乏可靠的生物标志物，HS 病变（SVL）是导致老年人痴呆的重要因素。在生命过程中，SVL 仍未被发现，且未被充分认识。这些限制阻碍了发展的努力。该项目的长期目标是改善这些药物的体内诊断。与死后脑部 MRI 相比，使用从死后脑部 MRI 获得的见解来研究重要的病理学。生命、死后 MRI 能够获得显着更高质量的扫描，从而实现更好的量化以及脑组织异常的定位。 90+ 研究，一项针对大学 90 岁或以上参与者的纵向观察研究加利福尼亚州欧文市提供了一个独特的机会来检查死后脑部 MRI 对最古老的人的效用目前正在对捐赠的大脑和相当大的部分进行神经病理学评估。一部分参与者将在一生中接受脑部 MRI 检查，以便对体内和尸检成像结果以及将尸检结果转化为体内 MRI 的结果。已经开发了序列并开始采集死后 MRI 扫描，证明我们的可行性我们预计会获得 50 名参与者的死后 MRI 扫描，并根据我们当前的数据，这样本将提供足够数量的包含两种感兴趣的病理学（即 HS 和 SVL）的病例。此外，我们的功效计算表明我们将能够用这个来测试该提案的假设样本大小。在目标 1 中，我们将检验海马硬化与 MRI 可检测体积相关的假设海马体的丢失和信号变化，死后 MRI 具有更高的灵敏度来检测这些与生前获得的 MRI 相比，在目标 2 中，我们将检验死后 MRI 允许的假设。与生前获得的 MRI 相比，检测到更多数量的 SVL。完成这项工作并利用从这项研究中获得的见解后，我们将申请 R01 补助金前瞻性研究死后 MRI 在预测大范围海马硬化和 SVL 中的效用从这些研究中获得的见解将用于预测 HS 并改进检测。一生中获得的 MRI 中的 SVL 将使随后能够开发针对该疾病的靶向疗法。这两种重要的病理学在增长最快的地区显着促进痴呆症的发展到 2050 年，我们的人口将占痴呆症患者总数的一半。