Cognitive and Neural Consequence of Long Term Cortisol Exposure in Human Aging.

长期接触皮质醇对人类衰老的认知和神经影响。

• 批准号: 7675255
• 负责人: SCOTT D. MOFFAT
• 金额: $ 33.79万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7675255
• 关键词: Adrenal Cortex Hormones; Adrenal Glands; Adverse effects; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Ancillary Study; Animal Experimentation; Animal Model; Animals; Atrophic; Baltimore; Biological Assay; Biological Neural Networks; Biometry; Brain; Cerebrovascular Circulation; Chronic; Cognition; Cognition Disorders; Cognitive; Cognitive aging; Collection; Complex; Data; Data Analyses; Data Set; Dementia; Development; Diagnosis; Disease Outcome; Elderly; Elderly woman; Endocrine system; Endocrinology; Engineering; Environment; Equipment; Evaluation; Exposure to; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Gonadal Steroid Hormones; Hippocampus (Brain); Hormonal; Hour; Human; Human Resources; Hydrocortisone; Immunoassay; Impaired cognition; Individual; Individual Differences; Intervention; Investigation; Knowledge; Lead; Literature; Long-Term Effects; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measures; Memory; Memory Loss; Methods; Modeling; National Institute on Aging; Neurocognitive; Neurophysiology - biologic function; Outcome; Outcome Measure; Participant; Performance; Population; Population Study; Positioning Attribute; Positron-Emission Tomography; Prevention; Publishing; Recording of previous events; Regression Analysis; Research; Research Personnel; Risk; Risk Factors; Sampling; Steroids; Stimulus; Structure; Support System; System; Testing; Time; Urine; Vulnerable Populations; Woman; Work; age difference; age related; age related cognitive change; aging population; base; brain volume; cognitive change; cognitive function; cognitive neuroscience; follow-up; frontal lobe; functional decline; hippocampal atrophy; hypothalamic-pituitary-adrenal axis; innovation; men; neuroimaging; primary outcome; programs; relating to nervous system; steroid hormone; success; time interval; treatment strategy; virtual reality; way finding

DESCRIPTION (provided by applicant): This revised proposal is being submitted as an investigator-initiated R01 application to the National Institute on Aging. There is considerable evidence from animal research that chronic exposure to high levels of adrenal corticosteroids causes atrophy of the hippocampus and contributes to age-related declines in memory. In humans, evidence suggests that similar adverse effects may accompany excess cortisol (C) exposure. The long term goal of this research is to investigate the possible consequences of variability among and within individuals in rates of change in endogenous C concentrations on cognitive and neural outcomes. The specific aims of our proposal are to evaluate the impact of long term cortisol concentration on i) risk for dementia ii) risk for cognitive decline iii) rates of change in regional brain volumes iv) rates of change in regional cerebral blood flow v) brain activation during spatial navigation. Our central hypothesis is that levels of C will be associated with increased risk for dementia, increased risk for cognitive decline and increased risk for neural dysfunction in the hippocampus and pre-frontal cortex. We plan to evaluate the influence of endogenous C measures on these neural outcomes by analysis of existing data from the Baltimore Longitudinal Study of Aging (BLSA). In this dataset, we have access to urine samples from BLSA participants spanning a time interval of up to 30 years. Immunoenzymatic assay of existing urine samples will allow determination of C levels as well as rates of C increases and/or decreases within and between individuals. Cortisol values will be used as the primary predictor in mixed model regression analyses of our cognitive and neural outcomes. Our primary outcome measures include diagnoses of dementia as well as cognitive assessments. In addition, a subset of BLSA participants have received brain MRI and PET scans (N = 158) for assessment of brain structure and function, respectively. In addition to the analysis of existing data, we propose an ancillary study. We propose to select 2 groups of subjects based on their history of C exposure for participation in a functional MRI assessment of spatial navigation. The proposed research is significant in that it that it will allow us to identify a putative risk factor for age-related declines in both cognitive and neural function and ultimately lead to possible treatment strategies to ameliorate or delay cognitive and neural dysfunction.

描述（由申请人提供）：该修订后的提案已作为调查员提出的R01申请提交给国家老龄化研究所。从动物研究中有大量证据表明，长期暴露于高水平的肾上腺皮质类固醇会导致海马萎缩，并导致与年龄相关的记忆下降。在人类中，有证据表明，类似的不良反应可能伴随着多余的皮质醇（C）暴露。这项研究的长期目标是研究内源性C浓度变化率对认知和神经结局的变化率的可能后果。我们提案的具体目的是评估长期皮质醇浓度对i）痴呆风险的影响II）认知下降的风险iii）区域大脑体积变化率IV iv）脑血流量变化率iv）区域大脑血流变化率v）空间导航期间大脑的脑部激活。我们的中心假设是，C的水平将与痴呆症的风险增加，认知能力下降的风险增加以及海马和额外额叶前皮质的神经功能障碍的风险增加有关。我们计划通过分析巴尔的摩衰老纵向研究（BLSA）的现有数据来评估内源性C测量对这些神经结局的影响。在此数据集中，我们可以访问BLSA参与者的尿液样本，该时间间隔最多30年。现有尿液样品的免疫酶测定将允许确定C水平以及C的C率增加和/或在个体之间和/或降低。在我们的认知和神经结局的混合模型回归分析中，皮质醇值将用作主要预测因子。我们的主要结果指标包括诊断痴呆症和认知评估。此外，BLSA参与者的一部分已经接受了大脑MRI和PET扫描（n = 158），以评估大脑结构和功能。除了对现有数据的分析外，我们还提出了一项辅助研究。我们建议根据他们的C暴露史选择2组受试者，以参与空间导航的功能性MRI评估。拟议的研究非常重要，因为它将允许我们确定认知和神经功能中与年龄相关的下降的假定风险因素，并最终导致可能改善或延迟认知和神经功能障碍的治疗策略。