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: 8467654
• 负责人: NAFTALI RAZ
• 金额: $ 49.61万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8467654
• 关键词: Acceleration; Acetylcholine; Acute; Adult; Adverse effects; Affect; Age; Aging; Aging-Related Process; Alleles; Alzheimer' s Disease; American; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Attention; Award; Biochemical; Biological; 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 Markers; 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

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