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。

基本信息

批准号：
8576081
负责人：
SCOTT D. MOFFAT
金额：
$ 19.5万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8576081
关键词：
Cognitive Neural Consequence Long Term

项目摘要

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）：此修订后的提案将作为研究者发起的 R01 申请提交给国家老龄化研究所。来自动物研究的大量证据表明，长期接触高水平的肾上腺皮质类固醇会导致海马体萎缩，并导致与年龄相关的记忆力下降。在人类中，有证据表明，过量的皮质醇 (C) 暴露可能会带来类似的副作用。这项研究的长期目标是调查个体之间和个体内部内源碳浓度变化率的变异性对认知和神经结果的可能影响。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 ii) 认知能力下降风险 iii) 区域脑容量变化率 iv) 区域脑血流量变化率 v) 大脑的影响空间导航期间激活。我们的中心假设是，C 水平与痴呆风险增加、认知能力下降风险增加以及海马和前额皮质神经功能障碍风险增加相关。我们计划通过分析巴尔的摩纵向衰老研究（BLSA）的现有数据来评估内源性碳测量对这些神经结果的影响。在此数据集中，我们可以获取 BLSA 参与者的尿液样本，时间间隔长达 30 年。对现有尿液样本的免疫酶分析将能够确定个体内部和个体之间的 C 水平以及 C 增加和/或减少的速率。皮质醇值将用作我们认知和神经结果的混合模型回归分析的主要预测因子。我们的主要结果指标包括痴呆症的诊断以及认知评估。此外，一部分 BLSA 参与者接受了脑 MRI 和 PET 扫描（N = 158），分别用于评估脑结构和功能。除了对现有数据的分析之外，我们还提出了一项辅助研究。我们建议根据 C 暴露史选择 2 组受试者参与空间导航的功能 MRI 评估。拟议的研究意义重大，因为它将使我们能够确定与年龄相关的认知和神经功能下降的假定危险因素，并最终导致改善或延迟认知和神经功能障碍的可能治疗策略。