Neural Correlates and Modifiers of Cognitive Aging

这个持续项目的目标是 1.目标1.描述不同脑老化的过程，重点放在最好的情况下 对成功衰老的自然主义研究。有了这一重点，这项研究将补充现有的大规模 典型老年病样本的纵向调查。我们的目标是检查最接近的 在未经选择的人类群体中发现成功的生理衰老。 2.目标2，通过检测变化来深入了解与年龄相关的差异性脑萎缩的机制 脑白质的显微结构和局部脑铁含量的间接指标。 3.目的3.评估与年龄相关的局部脑变化(体积、弥散和 磁化特性和铁含量)和三个认知领域的表现，已知 易受衰老影响：情节记忆、执行功能和处理速度。 4.目的4.研究血管危险因素(生理学和遗传性)作为大脑和大脑的修饰物的作用 认知老化。我们将继续研究亚临床水平的血管风险的影响。 由高血压、循环心脏危险因子(同型半胱氨酸、C反应蛋白)、 胰岛素升高以及与血管和代谢风险相关的基因变异(MTHFR C677T，IL1-p C511T、BDNFVal66Met、血管紧张素转换酶L/D、载脂蛋白EPound4、糖尿病危险基因及与特定基因相关的基因多态性 神经递质--乙酰胆碱、5-羟色胺、多巴胺)。 目标5.所有列出的目标的共同之处是采用纵向方法研究生物和认知变化 潜在增长曲线模型，允许估计老龄化轨迹的形状。 目标6.方法学贡献。在拟议的延期授权期内，我们计划启动几个 方法学研究，其中我们将比较手动容量测量和基于ROI的评估 脑白质完整性的各种半自动方法，希望能将那些方法改进到 水平可与“黄金标准”相媲美。

The goals of this continuing project are 1. Aim 1. To describe the course of differential brain aging vyith a focus on the best-case-scenario naturalistic study of successful aging. With that focus, the 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 unselected human population. 2. Aim 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 regional brain iron content. 3. Aim 3. To evaluate the links between age-related regional brain changes (volume, diffusion and magnetization properties, and iron content) and performance in three cognitive domains with known vulnerability to aging: episodic memory, executive functions, and speed of processing. 4. Aim 4. To examine the effect of vascular risk factors (physiological and genetic) as modifiers of brain and cognitive aging. We will continue our investigation into the effects of sub-clinical levels of vascular risk conveyed by elevated blood pressure, circulating cardiac risk factors (homocysteine, C-reactive protein), elevated insulin, and genetic variants associated with vascular and metabolic risk (MTHFR C677T, IL1-p C511T, BDNF Val66Met, ACE l/D, ApoEpound4, diabetes risk genes, and polymorphisms related to specific neurotransmitters - acetylcholine, serotonin, dopamine). Aim 5. Common to all listed aims is a longitudinal approach to study of biological and cognitive change with Latent Growth Curves models that allow estimation of the shape of the trajectories of aging. Aim 6. Methodological contributions. During the proposed extension award period, we plan to initiate several methodological investigations, in which we will compared manual volumetry and ROI-based evaluation of white matter integrity with various semi-automated methods, with a hope to improve those methods to the level comparable with the "golden standard."