Connectomics of Brain Aging and Dementia

 描述（由申请人提供）：这是我们针对PAR-14-281，与人类疾病相关的连接体：研究群体应该由患有与衰老相关的神经退行性疾病（如阿尔茨海默病）的个体组成（临床前、早发性和迟发性）、其他衰老性痴呆和/或年龄相关的认知障碍，如轻度认知障碍（早期、轻度和晚期MCI）。我们的研究计划的组织原则是这样一种想法，即老年人认知功能障碍的表达是两个独立过程的结果-第一个是与AD相关的神经病理学，第二个是血管疾病引起的神经病理学变化。虽然突触丢失、老年斑和神经元缠结是AD的功能和诊断标志，但血管疾病导致的结构变化降低了脑储备和代偿，导致临床DAT综合征的早期表达。这项工作是在人类连接组计划（HCP）的主持下完成的。我们将实施HCP LifeSpan成像方案，并将使用FOA中规定的HCP行为和认知评估。我们将从匹兹堡大学阿尔茨海默病研究中心招募200名患者：125名患有DAT，75名患有前驱AD。所有受试者将符合其综合征的研究级诊断标准，所有受试者都将在ADRC中进行积极随访。我们还将从正在进行的社区居住老人研究中招募200名50-89岁的认知正常个体。所有认知正常的个体将有至少5年的前期数据可用于本研究，以进行认知分类和提取健康相关数据。入组本HCP疾病相关研究的受试者将按年龄（50岁/10岁/组）分层，非裔美国人和女性的代表性相等。将选择200名个体（100名患者/100名对照）使用HCP脑磁图（MEG）方案进行额外的神经成像。每位参与者将提供HCP规定的人口统计学、行为和实验室数据。我们将获得与血管风险相关的数据。200人也将进行体内淀粉样蛋白成像，其中100人将进行2年的纵向随访。所有数据将根据HCP指南使用Connectome协调设施公开提供。在当地，我们将利用这些数据来解决与结构，功能，AD，衰老和血管疾病相关的特定问题，在多模态研究中利用MRI，fMRI，MEG和体内Aβ成像的差异优势。

 DESCRIPTION (provided by applicant): This is a resubmission of our application in response to PAR-14-281, Connectomes Related to Human Disease: research cohorts should be comprised of individuals with neurodegenerative diseases associated with aging such as Alzheimer's disease (preclinical, early- and late-onset), other dementias of aging, and/or age-related cognitive disorders such as Mild Cognitive Impairment (early, mild and late MCI). The organizing principle of our research plan is the idea that the expression of cognitive dysfunction in the elderly is the result of two independent processes - the first is the neuropathology associated with AD, and the second the neuropathological changes as a consequence of vascular disease. While synaptic loss, senile plaques, and neurofibrillary tangles are the functional and diagnostic hallmarks of AD, it is the structural changes as a consequence of vascular disease that reduce brain reserve and compensation, resulting in an earlier expression of the clinical DAT syndrome. This work is being completed under the auspices of the Human Connectome Project (HCP). We will implement the HCP LifeSpan imaging protocol, and will use the HCP behavioral and cognitive assessments as specified in FOA. We will enroll 200 individuals from the University of Pittsburgh Alzheimer's Disease Research Center: 125 with DAT and 75 with prodromal AD. All subjects will meet research-level diagnostic criteria for their syndromes, and all will be in active follow-up in the ADRC. We will also enroll 200 cognitively normal individuals, 50-89 years old, from ongoing studies of community-dwelling elders. All of the cognitively normal individuals will have had at least five years of antecedent data available to this study for the purpose of cognitive classification and extraction of health-related data. Th participants enrolled into this HCP disease-related study will be stratified by age (50/decade/group) with equal representation of African- Americans and women. 200 individuals (100 patients/100 controls) will be selected for additional neuroimaging using the HCP Magnetoencephalography (MEG) protocol. Each of the participants will contribute the HCP-specified demographic, behavioral and laboratory data. We will acquire data relative to vascular risk. 200 individuals will also have in vivo amyloid imaging, and 100 of these participants will have 2-year longitudinal follow-up. All of the data will be made publicly available under the HCP guidelines using the Connectome Coordination Facility. Locally, we will use these data to address specific questions related to structure, function, AD, aging and vascular disease in multi-modality studies leveraging the differential advantages of MRI, fMRI, MEG, and in vivo Aβ imaging.