Neural Correlates and Modifiers of Cognitive Aging

描述（由申请人提供）： 我们的目标是：1.描述差异性脑老化的过程，重点是成功老化的最佳情况自然主义研究。拟议的研究将补充现有的大规模纵向调查的典型老年样本。我们的目标是研究在不受控制的人群中发现的最接近成功的生理衰老。2.通过研究白色物质的显微结构变化和灰质中基础代谢的间接指标，深入了解年龄相关的差异性脑萎缩的机制。我们计划研究区域性脑萎缩是否与下层白色物质完整性降低和局部血管活动减少有关。 我们将通过测量白质疏松的程度和通过扩散张量（DTI）和磁化传递（MT）成像测量有髓纤维的完整性来评估白色物质的完整性。 将通过测量与血氧合程度相关的局部T2* 弛豫常数来评估局部血管变化。我们将介绍新的成像方法-多回波敏感加权成像（SWI），允许测量T2* 和局部场变化，具有更好的精度和分辨率，通过传统的梯度召回方法。3评估年龄相关的区域脑变化（体积、扩散和磁化特性以及基础代谢）与已知易受衰老影响的三个认知领域（情景记忆、执行功能和处理速度）的表现之间的联系。4.研究脑和认知老化的修饰因子-血管风险和遗传因素对差异性脑和认知老化的影响。通过研究血管危险因素对成人大脑和认知的剂量反应效应的可能性，我们希望提供了解病理学的数据。 因为参与这项研究的一些女性将接受激素替代疗法（HRT），我们将评估HRT对大脑衰老的潜在益处。 ApoE基因型在脑功能和认知功能重建中的调节作用也将被评估。 5.最后，所有列出的目标的共同之处是一个纵向的方法来研究生物和认知的变化。为了实现这一压倒一切的目标，我们计划将纵向潜在变量增长建模技术应用于我们的数据分析。这种方法的创新之处在于，这些技术是人口统计学、社会学和认知老化研究的主要内容。 我们预计这些建模技术将允许测试有关健康老年人局部大脑变化与特定认知技能之间关系的假设。

DESCRIPTION (provided by applicant): Our goals are: 1. To describe the course of differential brain aging with a focus on the best-case-scenario naturalistic study of successful aging. The proposed study will complement existing large-scale longitudinal investigations of typical geriatric samples. Our objective is to examine the closest approximation to successful physiological aging to be found in an uncontrolled human population. 2. To gain insights into mechanisms of age-related differential brain shrinkage by examining changes in microstructure of the white matter and indirect indices of basal metabolism in the gray matter. We plan to examine whether regional brain shrinkage is associated with reduced integrity of the underlymg white matter and reduced local vascular activity. We wil assess white matter integrity by measuring the extent of leukoaraiosis and by gauging intactness of the myelinated fibers through diffusion tensor (DTI) and magnetization transfer (MT) imaging. Local vascular changes will be assessed by measuring local T2* relaxation constants that are related to the degree of blood oxygenation. We will introduce new imaging method - multi-echo Susceptibility Weighted Imaging (SWI) that allow measurement of T2* and local field variations with better precision and resolution that by conventional gradient-recall methods. 3 To evaluate the links between age-related regional brain changes (volume, diffusion and magnetization properties, and basal metabolism) and performance in three cognitive domains with known vulnerability to aging: episodic memory, executive functions, and speed of processing. 4. To examine the effect of modifiers of brain and cognitive aging - the vascular risk and genetic factors on differential brain and cognitive aging. By examining the possibility of dose-response effect of vascular risk factors on adult brain and cognition we hope to provide the data against which pathology will be understood. Because some of the women who participate in the study will be on hormone replacement therapy (HRT), we will assess the potential benefits of HRT on brain aging. The modifying role of ApoE genotype in shaping the trafectories of brain and cognitive againg will be also assessed. 5. Finally, common to all listed aims is a longitudinal approach to study of biological and cognitive change. To attain that overriding goal, we plan to apply longitudinal latent-variable growth modeling techniques to the analysis of our data. The innovative aspect of that approach is that those techniques are the staple of demographic, social, and cognitive aging studies. We expect these modeling techniques will allow testing hypotheses about relations between regional brain changes and specific cognitive skills in healthy aging adults.