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

项目摘要/摘要 脑血管病变(CVP)和阿尔茨海默病(AD)病理(ADP)(淀粉样蛋白和tau)是 导致老年人认知障碍的两个主要过程。即使CVP功能已经 几十年来，没有一种方案可以将多种CVD特征集成到一个具有 预测能力可与AD生物标志物相媲美，并与认知功能相关。初级阶段 这笔赠款的目的是开发和验证一种基于成像的量化中心静脉压的指标，我们称之为 “CVD量表”[CVD-脑血管疾病]我们将使用一种循序渐进的方法来开发几种心血管疾病 基于从简单到复杂的MRI指标的增量信息进行扩展-FLAIR(白色 物质高信号(WMH、梗塞的大小和位置)、T2*GRE(皮质下微出血)和DTI (测量白质的WMH和周围WMH下的分数各向异性和平均扩散率 正直)。这些模型将通过对这些成像特征中的每一个根据其 对认知表现的贡献和最终的CVD量表将根据其能力进行分析选择 预测认知。我们将使用额外的独立数据集来确保我们的模型和 如有必要，请加以改进。由于基于尸检的脑血管病变标尺尚未发现 预测认知和/或难以在生前评估，病理结果将不被用于 规模的发展，但不是为了确认。资助金的次要目标是将 心血管疾病量表，以了解a)性别、载脂蛋白4和复原力测量(智力和身体)的影响 运动方式)在考虑了传统危险因素(糖尿病、高血压、 B)研究CVP和ADP之间的相互作用。我们会 利用现有的以人口为基础的和预期的梅奥老年临床研究(MCSA)队列和 获取新的成像数据(PIB PET、Tau PET、MRI)，用于开发CVD量表。人口-- MCSA样本的基本性质非常适合量表的开发和推广 因为它抓住了CVP的范围。该提案的优点之一是有计划地传播 将心血管疾病量表授予科学界。

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.