Multimodal MRI biomarkers of small vessel disease for older persons with and without dementia.

摘要 小血管病 (SVD) 病理在老年人的大脑中非常常见，并且与 认知能力下降、MCI 和痴呆症。 SVD 病理包括三种常见的血管疾病和 一系列相关的组织损伤。 SVD 病变本身可能会导致痴呆，但更为常见 与阿尔茨海默病 (AD) 和其他与年龄相关的疾病共存，它们降低了 失智。有效的参与者选择进入试验以及预防和治疗将大大受益 具有这种病理学的体内生物标志物。目前的生物标志物因缺乏 SVD 特异性而受到限制（与 SVD 相比）。 AD）病理学和缺乏病理学验证。我们建议通过（1）进一步克服这些障碍 在控制 AD 和其他疾病后，开发 SVD 病理的特定体外 MR 成像特征 患有或未患有痴呆症的人大脑中的病理现象； (2) 使用机器学习训练分类器 和多模态 MRI，并在非痴呆症患者中测试分类器，以及它是否与 临死时的认知状态； (3) 将分类器转化为体内生物标志物 研究了与血管危险因素和认知、MCI 和痴呆的关系； (4) 验证 单独队列中的生物标志物 (ADNI) 以及通过尸检确认一大群 SVD 病理学 对同意在死亡时进行尸检的老年人进行纵向 MRI 随访。最后我们建议（5）分享 UH2/UH3 联盟内的数据、专业知识和生物标志物策略，并交叉验证选定的 通过认知测试、抽血和脑部尸检对老年人的生物标志物进行纵向跟踪。 死亡时间。我们建议利用两个纵向临床影像病理学队列的资源， Rush 记忆与衰老项目 (MAP) (R01AG017917) 和宗教秩序研究 (ROS) （P30AG010161），以实现这些目标。

ABSTRACT Small vessel disease (SVD) pathologies are very common in the brains of older persons and are related to decline in cognitive abilities, MCI, and dementia. SVD pathologies include three common vessel diseases and an array of related tissue injuries. SVD pathologies may cause dementia on their own but more commonly coexist with Alzheimer's disease (AD) and other age-related pathologies where they lower the threshold for dementia. Effective participant selection into trials, and prevention and treatment would greatly benefit from having in-vivo biomarkers of this pathology. Current biomarkers are limited by lack of specificity for SVD (vs. AD) pathology and lack of pathologic validation. We propose to overcome these obstacles by (1) further developing specific ex-vivo MR imaging features of SVD pathologies after controlling for AD and other pathologies, in the brains of persons with and without dementia; (2) training a classifier using machine learning and multimodal MRI, and testing the classifier in persons without dementia, and whether it is related to cognitive status proximate to death; (3) translating the classifier into an in-vivo biomarker which can be investigated in relation to vascular risk factors and cognition, MCI, and dementia; and (4) validating the biomarker in a separate cohort (ADNI) and by autopsy confirmation of SVD pathologies in a large group of older persons followed longitudinally with MRI who agree to autopsy at death. Finally we propose to (5) share data, expertise and biomarker strategies within the UH2/UH3 consortium and cross-validate selected biomarkers in older persons followed longitudinally with cognitive testing, blood draws and brain autopsy at the time of death. We propose to leverage the resources of two longitudinal clinical-imaging-pathology cohorts, the Rush Memory and Aging Project (MAP) (R01AG017917) and Religious Orders Study (ROS) (P30AG010161), to accomplish these aims.