HOW DOES RESERVE MODIFY LINKS BETWEEN COGNITION & IMAGING INDICES OF AD PATHOLOGY

项目总结/摘要 虽然病理学是阿尔茨海默病（AD）中认知功能下降的根本原因，但 储备机制的受试者变异性解释了为什么有些受试者有更大的能力来最小化 疾病相关神经病理改变的临床表现。这项建议的主要目标是 研究储备措施如何改变病理和认知之间的关系。 将使用多模态PET和MRI成像生物标志物定量病理学。指导阶段：对于 研究的具体目标1，候选人将扩展其发表的结果，用于自动定量 从结构MRI（sMRI）中研究AD中的神经变性，以开发用于量化体内成像的算法 其他成像模式的病理学指标（PiB-PET：斑块负荷指标; FDG-PET： 神经元功能障碍的指标; FLAIR：血管疾病的指标沿着sMRI： 神经变性）。这些算法将被应用于计算特定模态的成像测量， 在我们的非痴呆人群为基础的队列，包括认知正常和轻度认知 受损主体。在此期间，她将接受克利福德·杰克博士的直接指导， 多模态成像方法在AD和博士大卫诺普曼在临床方面的老龄化和痴呆症。作为 作为拟议研究的一部分，候选人将参加认知神经科学和临床方法的课程 加强这里概述的多学科研究所需的技能。独立的相位 (R00)：在此阶段，将从功能连接度量中确定备用措施， 从静息状态fMRI和其他来源，如智力生活方式（教育，职业，认知 活动）和身体活动测量（身体活动和锻炼）。这些将应用于（目标2） 建立病理学的成像测量和认知表现之间的关系，以及这些 通过储备措施和与其他成像措施的相互作用， 病理在目标3中，建立病理学的影像学测量与 随着时间的推移，认知表现以及这些关系如何通过储备措施和 与病理学的其他成像测量的相互作用。

PROJECT SUMMARY/ABSTRACT Although pathology is the underlying cause of cognitive decline seen in Alzheimer's disease (AD), inter- subject variability in reserve mechanisms explains why some subjects have greater capacity to minimize the clinical expression of disease related neuropathological changes. The broad objective of this proposal is to investigate how measures of reserve modify the relationship between pathology and cognition. Pathology will be quantified using multi-modality PET and MRI imaging biomarkers. Mentored Phase: For Specific Aim 1 of the study, the candidate will extend her published results for automated quantification of neurodegeneration in AD from structural MRI (sMRI) to develop algorithms for quantifying in vivo imaging measures of pathology from other imaging modalities (PiB-PET: indicator of plaque burden; FDG-PET: indicator of neuronal dysfunction; FLAIR: indicator of cerebro-vascular disease along with sMRI: indicator of neurodegeneration). These algorithms will be applied to calculate modality-specific imaging measures of pathology in our non-demented population-based cohort consisting of cognitively normal and mild cognitive impairment subjects. During this time, she will receive direct mentorship from Dr. Clifford Jack in the area of multi-modality imaging methods in AD and Dr. David Knopman in clinical aspects of aging and dementia. As part of the proposed research, the candidate will take courses in cognitive neuroscience and clinical methods to strengthen the skill set necessary for the multi-disciplinary research outlined here. Independent Phase (R00): During this phase, measures of reserve will be identified from functional connectivity metrics derived from resting state fMRI and from other sources such as intellectual lifestyle (education, occupation, cognitive activities) and physical activity measure (physical activity and exercise). These will be applied (Aim 2) to establish the relationships between imaging measures of pathology and cognitive performance and how these relationships are modified by measures of reserve and by interactions with other imaging measures of pathology. And in Aim 3, establish the relationships between imaging measures of pathology and change in cognitive performance over time and how these relationships are modified by measures of reserve and by interactions with other imaging measures of pathology.