Neural Correlates and Modifiers of Cognitive Aging

认知衰老的神经相关因素和调节因素

• 批准号: 6927406
• 负责人: NAFTALI RAZ
• 金额: $ 60.35万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927406
• 关键词: age difference; aging; basal metabolism; brain circulation; brain imaging /visualization /scanning; brain mapping; brain metabolism; brain morphology; cardiovascular disorder risk; clinical research; cognition; diffusion magnetic resonance imaging; executive function; gene expression; gray matter; human subject; longitudinal human study; magnetic resonance imaging; mathematical model; memory; neural information processing; neuropathology; white matter

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.

描述（由申请人提供）：我们的目标是： 1. 描述差异性大脑衰老的过程，重点是成功衰老的最佳情况自然主义研究。拟议的研究将补充现有的典型老年样本的大规模纵向调查。我们的目标是检查在不受控制的人群中发现的最接近成功的生理衰老的情况。 2. 通过检查白质微观结构的变化和灰质基础代谢的间接指标，深入了解与年龄相关的差异性脑萎缩的机制。我们计划检查区域脑萎缩是否与底层白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以及通过扩散张量 (DTI) 和磁化转移 (MT) 成像测量有髓纤维的完整性来评估白质完整性。 通过测量与血液氧合程度相关的局部 T2* 弛豫常数来评估局部血管变化。我们将引入新的成像方法 - 多回波磁化率加权成像 (SWI)，与传统的梯度回忆方法相比，它可以以更高的精度和分辨率测量 T2* 和局部场变化。 3 评估与年龄相关的区域大脑变化（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的表现之间的联系：情景记忆、执行功能和处理速度。 4. 研究大脑和认知老化的调节因素——血管风险和遗传因素对大脑和认知老化差异的影响。通过检查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，我们希望提供理解病理学的数据。 由于参与该研究的一些女性将接受激素替代疗法 (HRT)，因此我们将评估 HRT 对大脑衰老的潜在益处。 还将评估 ApoE 基因型在塑造大脑轨迹和认知能力方面的修改作用。 5. 最后，所有列出的目标的共同点是采用纵向方法来研究生物和认知变化。为了实现这一首要目标，我们计划将纵向潜变量增长建模技术应用于数据分析。该方法的创新之处在于，这些技术是人口、社会和认知衰老研究的主要内容。 我们预计这些建模技术将能够测试有关健康老年人的区域大脑变化与特定认知技能之间关系的假设。