Neurobiologic Study of Psychological Distress & Dementia

心理困扰的神经生物学研究

基本信息

批准号：
7100832
负责人：
ROBERT S WILSON
金额：
$ 35.34万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2011-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of the proposed study is to identify the neurobiologic mechanisms underlying the association of psychological distress with dementia in aged humans. Recent research has shown that measures of psychological distress are related to risk of dementia and rate of cognitive decline but not with common age-related neuropathology associated with cognitive impairment (e.g., tau positive tangles, cerebral infarction). Based on a long history of mainly animal research, we hypothesize that psychological distress leads to neurodegenerative, stress hormone receptor, and neurotrophic changes in limbic structures that mediate the stress response and memory function, making the brain more vulnerable to common age-related pathology and increasing the likelihood that such pathology will be clinically expressed as dementia. The proposed study will take advantage of clinical and post-mortem data, and brain tissue, from older persons participating in the Religious Orders Study, all of whom agreed to annual detailed clinical evaluation and brain donation at the time of death. On post-mortem examination, we propose to quantify in three limbic regions neurons and dendrites, mineralocorticoid and glucocorticoid receptors, and the expression of brain-derived neurotrophic factor and its receptor and to examine their association with measures of psychological distress, dementia and cognitive function measured proximate to death. We then propose to examine the association of these post-mortem limbic indices with post-mortem indices of common age-related pathology (i.e., amyloid deposition, tangle formulation, cerebral infarction, Lewy bodies) and test the hypotheses that the post-mortem indices of limbic structure (i) mediate the association of psychological distress with incidence of dementia and level of cognition measured proximate to death and (ii) increase the likelihood that common age-related pathology is expressed clinically as dementia or cognitive impairment proximate to death.

描述（由申请人提供）：拟议研究的总体目标是确定老年人心理困扰与痴呆症之间关联的神经生物学机制。最近的研究表明，心理困扰的测量与痴呆风险和认知能力下降速度相关，但与与认知障碍相关的常见年龄相关神经病理学（例如 tau 阳性缠结、脑梗塞）无关。基于长期的主要动物研究历史，我们假设心理困扰会导致神经退行性、应激激素受体和介导应激反应和记忆功能的边缘结构的神经营养变化，使大脑更容易受到常见的与年龄相关的病理影响，增加了这种病理在临床上表现为痴呆的可能性。拟议的研究将利用参与宗教团体研究的老年人的临床和尸检数据以及脑组织，他们都同意在死亡时进行年度详细的临床评估和大脑捐赠。在尸检中，我们建议量化三个边缘区域的神经元和树突、盐皮质激素和糖皮质激素受体，以及脑源性神经营养因子及其受体的表达，并检查它们与心理困扰、痴呆和认知功能测量的关系测量接近死亡。然后，我们建议检查这些死后边缘系统指数与常见年龄相关病理学死后指数（即淀粉样蛋白沉积、缠结形成、脑梗塞、路易体）的关联，并测试死后指数的假设边缘结构的变化（i）介导心理困扰与痴呆症发生率和临死时测量的认知水平之间的关系，以及（ii）增加表达常见与年龄相关的病理的可能性临床上表现为痴呆或临近死亡的认知障碍。