Neural Correlates and Modifiers of Cognitive Aging

认知衰老的神经相关因素和调节因素

基本信息

批准号：
8281590
负责人：
NAFTALI RAZ
金额：
$ 54.52万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-09-30 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8281590
关键词：
Acceleration Acetylcholine Acute Adult Adverse effects Affect Age Aging Aging-Related Process Alleles Alzheimer&apos s Disease American Anti-Inflammatory Agents Anti-inflammatory Apoptosis Attention Award Biochemical Biological Biological Markers Biological Process Blood Blood Glucose Blood Pressure Blood Vessels Boxing Brain Brain region Brain-Derived Neurotrophic Factor C-reactive protein Cardiac Catalytic Domain Cell Differentiation process Cell Proliferation Cerebrum Chromosomes, Human, Pair 2 Chronic Clinical Cognition Cognitive Cognitive aging Cohort Effect Collection Compensatory Hyperinsulinemia Complement Computer software Cross-Sectional Studies Data Data Analyses Data Set Deceleration Desire for food Deterioration Diabetes Mellitus Diffusion Disease Dopamine Elderly Ensure Enzymes Episodic memory Evaluation Exhibits Experimental Diabetes Mellitus Family Genes Genetic Genetic Epistasis Genetic Polymorphism Genetic Risk Genetic Variation Genomics Genotype Glucokinase Glucose Glucose-6-Phosphate Glycosylated Hemoglobin Goals Growth HTR2A gene Health Hippocampus (Brain)Homocysteine Homocystine Homozygote Hospitals Human Hyperglycemia Hypertension Image Analysis Individual Individual Differences Inflammation Inflammatory Inflammatory Response Instruction Insula of Reil Insulin Insulin Resistance Interleukin-1 Interleukin-13 Interleukin-6 Investigation Iron KAI1 gene Knockout Mice Length Lesion Letters Light Link Literature Liver Location Longitudinal Studies MTHFR gene Magnetic Resonance Imaging Maintenance Manuals Measurement Measures Memory Metabolic Methodology Methods Mission Modeling Modification Morbidity - disease rate Muscarinic Acetylcholine Receptor Myelin Nature Neocortex Neurobiology Neurotransmitters Nicotinic Receptors Other Genetics Pancreas Participant Pattern Performance Personal Satisfaction Persons Phase Phosphorylation Physiologic pulse Physiological Play Population Predisposition Price Process Progress Reports Property Proteins Proxy Publishing Pulse Pressure Relative (related person)Reliance Reporting Research Resources Risk Risk Factors Role Sampling Sampling Studies Serotonin Shapes Short-Term Memory Site Solutions Speed Stimulus Structure Surface System Testing Time Training Universities Variant Vascular Dementia Ventricular Vertebral column Work age effect age related aging brain area striata base blood glucose regulation blood pressure regulation brain shape brain volume calcium metabolism cardiovascular risk factor caudate nucleus cholinergic cognitive change cohort cytokine design diabetes risk executive function fasting glucose follow-up genetic risk factor genetic variant glucose metabolism glucose sensor glucose uptake glucose-6-phosphatase glycemic control healthy aging human TCF7L2 protein improved indexing insight instrument insulin sensitivity interest iron metabolism longitudinal analysis meetings member metabolic abnormality assessment neocortical neuroimaging normal aging presynaptic processing speed receptor relating to nervous system research study response sex skills synaptogenesis trend way finding white matter

项目摘要

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."

这个持续项目的目标是 1. 目标 1. 重点描述最佳情况下大脑老化的差异过程成功衰老的自然主义研究。以此为重点，该研究将补充现有的大规模研究对典型老年人样本的纵向调查。我们的目标是检查最接近的近似值在未经选择的人群中发现成功的生理衰老。 2. 目标 2，通过检查变化来深入了解与年龄相关的大脑差异性萎缩的机制白质微观结构和区域脑铁含量的间接指标。 3. 目标 3. 评估与年龄相关的区域大脑变化（体积、扩散和变化）之间的联系磁化特性和铁含量）以及已知的三个认知领域的表现衰老的脆弱性：情景记忆、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）作为大脑和神经功能调节剂的影响认知老化。我们将继续研究亚临床水平的血管风险的影响由血压升高、循环心脏危险因素（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遗传变异（MTHFR C677T、IL1-p C511T、BDNF Val66Met、ACE l/D、ApoEpound4、糖尿病风险基因以及与特定相关的多态性神经递质 - 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采用纵向方法来研究生物和认知变化潜在生长曲线模型可以估计衰老轨迹的形状。目标 6. 方法论贡献。在拟议的延长奖励期内，我们计划启动几项方法学研究，其中我们将比较手动体积测定和基于 ROI 的评估使用各种半自动化方法检测白质完整性，希望将这些方法改进到水平堪比“黄金标准”。