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

项目摘要/摘要 虽然病理是阿尔茨海默病(AD)患者认知功能下降的根本原因，但在阿尔茨海默病(AD)中， 储备机制中的主体变异性解释了为什么一些主体具有更大的能力来最小化 疾病相关神经病变的临床表现。这项提议的总体目标是 研究储备措施如何改变病理和认知之间的关系。 病理将使用多模式PET和MRI成像生物标记物进行量化。指导阶段：用于 研究的具体目标1，候选人将扩展她发布的结果，以实现自动量化 阿尔茨海默病的结构磁共振成像(SMRI)中的神经退行性变研究体内成像的量化算法 其他成像方式的病理测量(PIB-PET：斑块负荷指标；FDG-PET： 神经元功能障碍的指标；FLAIR：脑血管疾病的指标以及sMRI：指标 神经退行性变)。这些算法将被应用于计算特定于医疗设备的成像测量 由认知正常和轻度认知组成的非痴呆人群队列的病理学 损伤受试者。在此期间，她将在以下领域接受Clifford Jack博士的直接指导 AD和David Knopman博士在衰老和痴呆临床方面的多模式成像方法。AS 作为拟议研究的一部分，候选人将学习认知神经科学和临床方法的课程。 以加强这里概述的多学科研究所需的技能。独立相 (R00)：在此阶段，将根据得出的功能连接性指标确定储备措施 从静息状态功能磁共振成像和其他来源，如智力生活方式(教育、职业、认知 活动)和体力活动测量(体力活动和锻炼)。这些将应用于(目标2) 建立病理的影像测量和认知表现之间的关系，以及这些关系是如何 通过储备测量以及通过与其他成像测量的交互来修改关系 病理学。在目标3中，建立病理的影像指标与血管病变之间的关系 随着时间的推移的认知表现，以及这些关系是如何通过储备和 与其他病理成像方法的相互作用。

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.