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

描述(申请人提供)：虽然病理是阿尔茨海默病(AD)患者认知能力下降的根本原因，但储备机制中的不同受试者之间的差异解释了为什么一些受试者有更大的能力将疾病相关神经病理变化的临床表现降至最低。这项建议的总体目标是调查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：为了研究的具体目标1，候选人将扩展她发表的从结构磁共振成像(SMRI)自动量化AD中神经退行性变的结果，以开发算法来量化来自其他成像方式的体内病理成像测量(PIB-PET：斑块负荷指示器；FDG-PET：神经元功能障碍指示器；FLAIR：脑血管疾病指示器以及sMRI：神经变性指示器)。这些算法将被应用于我们的非痴呆人群队列中计算特定形态的病理成像测量，该队列由认知正常和轻度认知障碍受试者组成。在此期间，她将在AD的多模式成像方法领域接受Clifford Jack博士的直接指导，在衰老和痴呆的临床方面接受David Knopman博士的直接指导。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方面的课程，以加强这里概述的多学科研究所必需的技能。独立阶段(R00)：在这一阶段，将根据静息状态功能磁共振成像得出的功能连通性指标以及其他来源，如智力生活方式(教育、职业、认知活动)和体力活动衡量标准(体力活动和锻炼)来确定储备衡量标准。这些将被应用(目标2)来建立病理成像测量和认知表现之间的关系，以及如何通过储备测量以及通过与其他病理成像测量的相互作用来修改这些关系。在目标3中，建立病理成像测量与认知表现随时间的变化之间的关系，以及这些关系如何被储备测量以及与其他病理成像测量的交互作用所修正。

DESCRIPTION (provided by applicant): 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.