基于空间协方差分析建立的AD和SIVD脑灌注模式：生物标志物和机制研究

尽管脑灌注减低是阿尔茨海默病（AD）和皮层下缺血性血管性痴呆（SIVD）重要的共同发病机制，其临床意义及病理生理作用和机制并不明确。以往动脉自旋标记（ASL）MRI的AD和SIVD脑灌注研究结果不一致，也不便用于临床个体评价。申请人前期通过多因素的空间协方差分析成功获得年龄相关的ASL脑灌注模式，比传统方法更符合脑功能的网络机制；并进一步通过计算个体表达值对单个个体进行定量分析，可有效区分年轻组和年老组。本课题将以双探针PET辅助诊断的队列为研究对象，建立AD和SIVD相关的脑灌注模式，评价其对疾病早期诊断、鉴别诊断和预测进展的价值，比较其与脑结构和脑代谢模式、白质病变和淀粉样蛋白沉积的关系。同时，探索与不同认知领域相关的脑结构、脑灌注和脑代谢模式。本研究将为ASL检测的脑灌注模式在AD和SIVD诊治中的临床应用提供依据，并揭示脑灌注改变的病理生理作用和机制，以及认知障碍的神经网络基础。

Although cerebral hypoperfusion is the common pathogenesis for Alzheimer’s disease (AD) and subcortical ischemic vascular dementia (SIVD), its clinical implication and pathophysiological actions and mechanisms are still unclear. Arterial spin labeling (ASL) with MRI has been investigated in patients with AD or SIVD for detecting regional changes in cerebral perfusion. However, the findings from previous studies are neither consistent nor appropriate for single-case evaluation in clinical practice. An age-related perfusion pattern measured with ASL has been obtained using a novel spatial covariance analysis (SCA) method of scaled subprofile model/principal component analysis (SSM/PCA) in our previous research. Compared with traditional univariate methods, the pattern derived from multivariate SCA is more consistent with altered large-scale network connection among functional brain regions inherent in diseased states. We further quantified its expression in individual subject by calculating the subject score of this pattern, which correlated significantly with age and could robustly distinguish younger group and older group. In this study, we plan to establish AD-related and SIVD-related perfusion patterns measured with ASL using the method of SCA in a prospectively enrolled patient cohort with both FDG and PiB PET assessments. Our primary aims are (1) to evaluate the use of these perfusion patterns for early diagnosis, differential diagnosis, and monitoring of disease progression in AD and SIVD; (2) to compare the association between perfusion pattern, structural pattern, metabolic pattern, white matter lesions, and amyloid deposition. Our secondary aim is to explore the feasibility of identifying perfusion, structural and metabolic patterns associated with deficits in different cognitive domains in each of these disease conditions. The findings of this research will facilitate the application of perfusion patterns measured with ASL in clinical diagnosis and management of AD and SIVD, reveal pathophysiological actions and mechanisms underlying perfusion changes, and shed light on neurobiological basis of functional and anatomical brain network correlates of cognitive dysfunction.