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，与以下因素有关： 认知能力下降、MCI和痴呆。SVD病理包括三种常见的血管疾病， 一系列相关的组织损伤SVD病理本身可能导致痴呆，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 痴呆有效地选择参与试验的受试者，以及预防和治疗将大大受益于 具有这种病理学的体内生物标志物。目前的生物标志物由于缺乏对SVD的特异性而受到限制（与 AD）病理学和缺乏病理学验证。我们建议通过以下措施克服这些障碍：（1）进一步 在控制AD和其他疾病后，开发SVD病理的特定离体MR成像特征 （2）使用机器学习训练分类器 和多模态MRI，并在没有痴呆的人中测试分类器，以及它是否与 接近死亡的认知状态;（3）将分类器翻译成体内生物标志物，其可以 研究与血管危险因素和认知、MCI和痴呆的关系;以及（4）验证 在一个单独的队列（ADNI）中的生物标志物，以及在一个大的 同意死亡时尸检的老年人进行MRI纵向随访。最后，我们建议（5）分享 UH 2/UH 3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 老年人的生物标志物随后进行了纵向认知测试，抽血和脑尸检。 死亡时间我们建议利用两个纵向临床-成像-病理学队列的资源， 拉什记忆和衰老项目（MAP）（R 01 AG 017917）和宗教秩序研究（ROS） #30301;，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.