Neural Correlates and Modifiers of Cognitive Aging

描述(由申请者提供)：我们的目标是：1.描述不同的脑老化过程，重点放在成功衰老的最佳案例-场景自然主义研究上。拟议的研究将补充现有的对典型老年样本的大规模纵向调查。我们的目标是检验在不受控制的人群中发现的与成功的生理衰老最接近的情况。2.通过检测脑白质微结构的变化和灰质基础代谢的间接指标，深入了解增龄性脑萎缩的机制。我们计划检查局部脑萎缩是否与淋巴下白质的完整性降低和局部血管活动减少有关。我们将通过测量脑白质疏松的程度以及通过弥散张量(DTI)和磁化转移(MT)成像测量有髓纤维的完整性来评估白质的完整性。局部血管变化将通过测量与血液氧合程度有关的局部T2*松弛常数来评估。我们将推出新的成像方法-多回波磁化率加权成像(SWI)，它可以测量T2*和局部场变化，比传统的梯度回忆法具有更高的精度和分辨率。3评估与年龄相关的局部脑变化(体积、扩散和磁化特性以及基础代谢)与三个已知易受衰老影响的认知域的表现之间的联系：情景记忆、执行功能和处理速度。4.探讨脑和认知老化的调节因子--血管风险和遗传因素对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对大脑老化的潜在好处。此外，还将评估载脂蛋白E基因在塑造大脑和认知衰老悲剧中的调节作用。5.最后，所有列出的目标的共同点是研究生物学和认知变化的纵向方法。为了实现这一最重要的目标，我们计划将纵向潜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、社会和认知老龄化研究的主要内容。我们预计，这些建模技术将允许测试关于健康老年成年人的局部大脑变化和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.