Development, Validation, and Application of an Imaging based CVD Scale

项目总结/摘要 脑血管病理学（CVP）和阿尔茨海默病（AD）病理学（ADP）（淀粉样蛋白和tau蛋白）是治疗阿尔茨海默病的最佳方法。 导致老年人认知障碍的两个主要过程。尽管CVP功能已被 几十年来，没有一种方案将CVD特征的多样性整合到一个度量中， 预测能力与AD生物标志物相当，并与认知功能相关。主 这项资助的目的是开发和验证一种基于成像的量化CVP的指标，我们称之为 “CVD量表”[CVD -脑血管疾病]。我们将使用逐步的方法来开发几个CVD 基于从简单到更复杂的MRI指标的增量信息的量表- FLAIR（白色 高信号物质（WMH）、梗死的大小和位置）、T2* GRE（皮质下微出血）和DTI （WMH和周围WMH下的分数各向异性和平均扩散率，以测量白色物质 完整性）。模型将通过根据它们的成像特征对这些成像特征中的每一个进行加权来开发。 将根据其对认知表现的贡献和最终CVD量表的分析选择， 预测认知。我们将使用额外的独立数据集，以确保我们的模型的通用性， 必要时加以改进。由于基于尸检的脑血管病变量表尚未发现 预测认知和/或难以评价死前，病理学结局将不用于 发展规模，而是为了确认。补助金的第二个目的是应用 CVD量表，以了解a）性别、APOE 4和复原力指标（智力和身体）的影响 活动生活方式）对CVP演变的影响， 血脂异常、心房纤颤、吸烟），和B）研究CVP和ADP之间的相互作用。我们将 利用现有的基于人群的前瞻性马约诊所老龄化研究（MCSA）队列， 获取新的成像数据（PIB PET、Tau PET、MRI），用于开发CVD量表。人口- MCSA样本的基础性质非常适合量表的开发和推广 因为它捕捉到了中心静脉压的范围。该建议的优点之一是有计划地传播 心血管疾病的等级

PROJECT SUMMARY / ABSTRACT Cerebrovascular Pathologies (CVP) and Alzheimer's disease (AD) pathologies (ADP) (amyloid and tau) are the two principal processes that drive cognitive impairment in the elderly. Even though CVP features have been available for decades, there is no scheme that integrates the multiplicity of CVD features into a metric that has predictive power comparable to the AD biomarkers and correlates with cognitive functioning. The primary objective of this grant is to develop and validate an imaging based metric for quantifying CVP which we call the “CVD scale” [CVD - Cerebrovascular Disease]. We will use a stepwise approach to develop several CVD scales based on incremental information going from simple to more complex MRI metrics - FLAIR (white matter hyperintensities (WMH), size and location of infarctions), T2* GRE (subcortical microbleeds), and DTI (Fractional anisotropy and mean diffusivity underlying WMH and surrounding WMH to measure white matter integrity). The models will be developed by weighting each of these imaging features according to their contribution to cognitive performance and the final CVD scale will be analytically selected based on its ability to predict cognition. We will use additional independent datasets to ensure the generalizability of our models and improve them if necessary. Since autopsy based scales for cerebrovascular lesions have not found to be predictive of cognition and/or difficult to evaluate antemortem, pathology outcomes will not be used for the development of the scale, but instead for confirmation. The secondary objective of the grant is to apply the CVD scale to understand a) the impact of sex, APOE4, and resilience measures (intellectual and physical activity lifestyle) on the evolution of CVP after accounting for traditional risk factors (diabetes, hypertension, dyslipidemia, atrial fibrillation, smoking), and b) investigate interactions between CVP and ADP. We will capitalize on the existing population-based and prospective Mayo Clinic Study of Aging (MCSA) cohort and acquire new imaging data (PIB PET, Tau PET, MRI) for the development of the CVD scale. The population- based nature of the MCSA sample is ideally suited for the development and generalizability of the scale because it captures the range of CVP. One of the strengths of the proposal is the planned dissemination of the CVD scale to the scientific community.