Stress and the Development of Alzheimer's Disease

压力与阿尔茨海默病的发展

• 批准号: 7007302
• 负责人: GUERRY Marie PEAVY
• 金额: $ 18.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7007302
• 关键词: Alzheimer' s disease; clinical research; cognition disorders; cortisol; dementia; glucocorticoids; hippocampus; human subject; interview; longitudinal human study; memory disorders; neurons; neuropsychological tests; physiologic stressor; psychological stressor; questionnaires; synapses

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a neurodegenerative disorder that results in the insidious onset and gradual progression of deficits in memory and other cognitive and functional abilities. The neuropathologic changes associated with AD begin in the hippocampus and surrounding areas, brain regions known to be crucial for memory. Recent conceptualizations of AD suggest that these changes begin well before clinical symptoms become apparent, and that the onset of symptoms and their progression may be influenced by any comorbid factor that increases neuronal vulnerability in these regions. One potential comorbid factor is chronic psychological stress. Numerous studies have shown that chronic stress results in the release of glucocorticoids that target the brain and exert their actions primarily on the hippocampus, with consequent loss of neurons and synapses and decline in memory. This suggests that comorbid, prolonged stress will adversely affect the integrity of mesial temporal structures and, as a result, will hasten the development of the dementia syndrome that characterizes AD in individuals who are likely to be in a preclinical phase. One such group, those with Mild Cognitive Impairment (MCI), have been identified as having memory complaints, mild memory loss on objective psychometric testing, and little or no loss of other cognitive functions or skills in activities of daily living. The present project will compare older, normal control and MCI subjects on measures of baseline psychological and physiological (cortisol) stress, with attention to the reactions of MCI subjects to potentially stressful events and difficulties, including loss of memory. Taking into account other risk factors for AD (e.g., age, APOE status), the project will determine the degree to which psychological and physiological stress sustained over time, increase susceptibility to cognitive decline, particularly memory loss, and conversion to clinically apparent AD, in subjects with MCI. If memory decline and the development of dementia are exacerbated by chronic stress in individuals with preclinical AD, behavioral and/or psychopharmacological means of ameliorating stress could delay the onset of clinical symptoms of AD by months or even years.

描述（由申请人提供）：阿尔茨海默氏病（AD）是一种神经退行性疾病，导致记忆中缺陷以及其他认知和功能能力的阴险发作和逐渐发展。与AD相关的神经病理学变化始于海马及周边地区，大脑区域已知对于记忆至关重要。 AD的最新概念表明，这些变化在临床症状显而易见之前就开始良好，并且症状的发作及其进展可能会受到增加这些地区神经元脆弱性的任何合并因子的影响。一个潜在的合并因素是慢性心理压力。大量研究表明，慢性应激会导致糖皮质激素释放，这些糖皮质激素针对大脑并主要在海马上发挥作用，因此神经元和突触的丧失以及记忆的下降。这表明合并症，延长的压力将对介体时间结构的完整性产生不利影响，结果，将加快痴呆综合征的发展，这些痴呆综合征的发展是在可能处于临床前阶段的个体中AD的表征。这样的群体是那些患有轻度认知障碍（MCI）的人，已被确定为记忆力投诉，客观心理测试中的轻度记忆力丧失以及日常生活活动中其他认知功能或技能几乎没有或没有丧失。本项目将在基线心理和生理（皮质醇）压力的措施中比较较旧的，正常的控制和MCI受试者，并注意MCI受试者对潜在压力事件和困难的反应，包括记忆的丧失。考虑到AD的其他风险因素（例如，年龄，APOE状态），该项目将确定心理和生理压力随着时间的流逝而持续的程度，增加了认知能力下降的敏感性，尤其是记忆力丧失，以及在MCI受试者中转变为临床明显的AD。如果临床前AD的个体的慢性应激，行为和/或心理药理学的改善压力的慢性压力会加剧记忆力下降和痴呆症的发展，则可以将AD的临床症状延迟到几个月甚至几年中。