Neural Correlates and Modifiers of Cognitive Aging

这个持续项目的目标是 1.目标1。描述差异性脑老化的过程，重点关注最佳情况 成功衰老的自然主义研究。有了这个重点，这项研究将补充现有的大规模 典型老年人样本的纵向调查。我们的目标是检验最接近的近似 成功的生理老化的可能性。 2.目的2，通过研究年龄相关的差异性脑萎缩的变化， 白色物质显微结构和局部脑铁含量的间接指标。 3.目标3。评估年龄相关的脑局部变化（体积、弥散和 磁化性质和铁含量）和性能在三个认知领域与已知的 易老化：情节记忆，执行功能和处理速度。 4.目标4。检查血管危险因素（生理和遗传）作为脑和 认知老化我们将继续研究亚临床水平血管风险的影响 由血压升高、循环心脏风险因素（同型半胱氨酸、C反应蛋白）、 胰岛素水平升高，以及与血管和代谢风险相关的遗传变异（MTHFR C677 T，IL 1-p C511 T、BDNF Val 66 Met、ACE 1/D、ApoEpound 4、糖尿病风险基因和与特定的 神经递质-乙酰胆碱、血清素、多巴胺）。 目标5。所有列出的目标的共同点是纵向研究生物和认知变化的方法， 潜在增长曲线模型，允许估计衰老轨迹的形状。 目标6。方法上的贡献。在建议的延长奖励期内，我们计划启动几个 方法学研究，其中我们将比较手动容量法和基于ROI的评估， 白色物质的完整性与各种半自动化的方法，希望能改善这些方法， 与“黄金标准”相当的水平。"

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."