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

描述（由申请人提供）：尽管病理学是阿尔茨海默病（AD）中观察到的认知下降的根本原因，但储备机制的受试者间差异解释了为什么一些受试者具有更大的能力来最小化疾病相关神经病理学变化的临床表达。这项建议的广泛目标是调查储备措施如何修改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，候选人将扩展其已发表的结构MRI（sMRI）自动定量AD神经退行性变的结果，以开发用于定量其他成像方式（PiB-PET：斑块负荷指标; FDG-PET：神经元功能障碍指标; FLAIR：血管疾病指标，沿着sMRI：神经退行性变指标）的病理学体内成像指标的算法。这些算法将应用于计算我们的非痴呆人群队列（由认知正常和轻度认知障碍受试者组成）中的病理形态特异性成像指标。在此期间，她将在AD的多模态成像方法领域接受Clifford Jack博士的直接指导，在衰老和痴呆的临床方面接受大卫Knopman博士的指导。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课程，以加强这里概述的多学科研究所需的技能。独立阶段（R 00）：在此阶段，将从静息状态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））获得的功能连接指标中确定储备措施。这些将被应用（目的2），以建立病理学成像措施和认知能力之间的关系，以及如何通过储备措施和与其他病理学成像措施的相互作用来修改这些关系。在目标3中，建立病理学成像测量与认知表现随时间变化之间的关系，以及这些关系如何通过储备测量以及与其他病理学成像测量的相互作用进行修改。

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.