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

摘要 小血管病变(SVD)在老年人的大脑中非常常见，与 认知能力下降、MCI和痴呆症。SVD的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的病理本身可能会导致痴呆，但更常见的是 与阿尔茨海默病(AD)和其他年龄相关的病理共存，它们降低了 痴呆症。有效的参与者选择进入试验，预防和治疗将大大受益于 体内有这种病理的生物标记物。目前的生物标记物受到SVD缺乏特异性的限制(与 AD)病理，缺乏病理证实。我们建议通过(1)进一步克服这些障碍 在控制AD和其他因素后，建立SVD病理的特异性体外磁共振成像特征 病理学，痴呆症患者和非痴呆症患者的大脑；(2)使用机器学习训练分类器 和多模式MRI，并在非痴呆症患者中测试分类器，以及它是否与 接近死亡的认知状态；(3)将分类器转换为体内生物标记物，可以 研究与血管危险因素和认知、MCI和痴呆症的关系；以及(4)验证 单独队列中的生物标记物(ADNI)和一大群SVD病理的尸检确认 老年人进行了纵向核磁共振检查，他们同意在死亡时进行尸检。最后我们建议(5)分享 UH2/UH3联盟内的数据、专业知识和生物标记战略，并交叉验证选定的 老年人的生物标志物在纵向上进行了认知测试、抽血和脑部尸检 死亡时间。我们建议利用两个纵向临床-影像-病理队列的资源， 快速记忆和衰老项目(MAP)(R01AG017917)和宗教秩序研究(ROS) (P30AG010161)，以达到这些目的。

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.