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

• 批准号: 10370734
• 负责人: Seyed Ahmad Sajjadi
• 金额: $ 25.18万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 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/10370734
• 关键词: 3-Dimensional; Age; Aged, 80 and over; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Area; Atrophic; Autopsy; Biological Markers; Brain; California; Characteristics; Custom; Data; Dementia; Detection; Development; Diagnosis; Disease; Goals; Gold; Grant; Hippocampus (Brain); Image; Individual; Kava; Lacunar Infarctions; Lead; 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; base; 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

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.

最古老的老年人，年龄在90岁以上，是全球增长最快的部分 痴呆症患病率惊人的人口。与年轻人不同，阿尔茨海默氏病 神经病理学（ADNP）不再是最古老和古老的和 痴呆通常是由于存在多种神经病理学。海马硬化症（HS）和小血管 病变（SVL）是最古老的痴呆症的重要因素。由于缺乏可靠的生物标志物，HS 仍然未被发现，SVL在生活中被低估了。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项目的体内诊断 使用从尸体后脑MRI中获得的见解的重要病理。与在 生活，验尸MRI具有明显更高质量扫描的能力，可以更好地量化 和脑组织异常的定位。 这项90多个研究，一项对大学或90岁以上参与者的纵向观察研究 欧文（Irvine）的加利福尼亚州提供了一个独特的机会，可以检查最古老的验尸脑MRI的实用性 老的。目前正在对捐赠的大脑进行神经病理学评估，并考虑 参与者的子集将在生命中进行大脑MRI，以便在体内和体内进行比较 验尸成像发现和从验尸获得到体内MRI的见解的翻译。我们有 已经开发了序列并开始获取后验尸MRI扫描证明了我们的可行性 方法。我们预计对50名参与者的验尸MRI扫描进行，并根据我们当前的数据，这 样本将提供足够数量的病例，这些病例具有感兴趣的两种病理，即HS和SVL。 此外，我们的功率计算表明，我们将能够使用此提案来检验该提案的假设 样本量。 在AIM 1中，我们将测试以下假设：海马硬化将与MRI可检测体积有关 海马的损失和信号变化，该验尸MRI具有更高的敏感性来检测这些 与生命中获得的MRI相比。在AIM 2中，我们将检验以下假设：验尸MRI允许 与生命中获得的MRI相比，检测较高的SVL数量。 完成这项工作并利用本研究中获得的见解，我们将申请R01赠款 前瞻性研究验尸MRI在大型海马硬化和SVL中的预测中的效用 队列。从这些研究中获得的见解将用于实现HS的预测并改善检测 在生命中获得的MRIS中的SVL。随后，这将使有针对性的疗法开发 这两种重要的病理极大地有助于痴呆症的发展最快的生长 到2050年，我们人口的一部分将代表所有患有痴呆症的人的一半。