Psychosocial stressors and the hippocampal memory system in African American seniors

项目总结/摘要 非裔美国人比欧洲血统的美国人有更大比例的阿尔茨海默病 （AD）。造成这种健康差距的根本原因尚不清楚。非洲裔美国老人表演 在一系列认知测试中比白色老年人差。社会经济和健康状况的差异 这一差距的很大一部分，但差异仍然存在。虽然种族没有生物学基础， 与种族少数地位有关的是非裔美国人中一个突出的慢性心理社会压力源，它对健康有负面影响，导致肥胖、高血压和其他疾病。这表明，由于种族主义的经验，心理社会慢性压力可能会导致AD和认知的健康差距。海马体是一个对学习和记忆至关重要的大脑区域，它与内嗅皮层一起， 受到AD和慢性压力的负面影响。应激模型表明，海马体中的成年神经发生率（成年大脑中新神经元的产生）受到负面影响 慢性压力衰老和AD此外，海马和内嗅皮层有高浓度 糖皮质激素受体，这是“应激激素”皮质醇的结合位点。另一个完善的 成人神经发生的调节剂是有氧运动。有氧运动和慢性压力都是有效的，但 与成人神经发生的调节剂相反。增加身体活动是减缓衰老和AD认知能力下降的最有效干预措施之一。本研究的目的是研究由于种族主义经历引起的心理社会慢性压力如何影响海马记忆系统（Aim 1），并研究中等强度的体力活动与海马功能和结构之间的关联 (Aim 2A）将非洲裔美国老年人与欧洲血统的老年人进行比较。我们会调查 皮质醇，在唾液中测量，是否介导，即解释，慢性压力和大脑之间的关联 完整性，以及中等强度的体力活动与种族之间是否存在适度的相关性 慢性应激与海马体和已知受AD影响的皮质区域的完整性之间的关系 (Aim 2B）。我们将通过高分辨率的功能和结构MRI来检查大脑， 完整这些神经成像技术具有放大齿状回子区域的分辨率， 海马，这是成年神经发生发生的主要区域，同时允许检查皮质AD特征区域。我们将利用非洲裔美国人队列的可用性， 波士顿大学阿尔茨海默病中心老年人健康外展计划（HOPE）登记处。 这项工作可能会产生一个新的假设：个人经历慢性心理社会压力， 种族主义可能表现出与AD一致的加速认知衰退。在未来，这个新的假设可能 然后通过纵向跟踪HOPE参与者进行测试，并将运动训练作为调节剂进行检查。减少美国种族/民族群体之间的AD健康差异是一个关键的公共卫生目标。

PROJECT SUMMARY / ABSTRACT A larger percentage of African Americans than Americans of European ancestry have Alzheimer's disease (AD). The underlying causes of this health disparity are not well understood. African American seniors perform worse than white seniors on a range of cognitive tests. Differences in socioeconomic and health status account for large portions of this disparity, but differences remain. Although race has no biological basis, discrimination related to racial minority status is a salient chronic psychosocial stressor in African Americans that has negative health consequences, contributing to obesity, hypertension, and other conditions. This suggests that psychosocial chronic stress due to experiences of racism may contribute to the health disparities in AD and cognition. The hippocampus is a brain area critical for learning and memory that, together with the entorhinal cortex, is negatively impacted by both AD and chronic stress. Stress models have shown that the rate of adult neurogenesis in the hippocampus, which is the generation of new neurons in the adult brain, is negatively affected by chronic stress, aging, and AD. In addition, the hippocampus and entorhinal cortex have a high concentration of glucocorticoid receptors, which are binding sites for the “stress hormone” cortisol. Another well-established modulator of adult neurogenesis is aerobic exercise. Aerobic exercise and chronic stress are both potent, but opposite modulators of adult neurogenesis. Increasing physical activity is one of the most effective interventions for slowing down cognitive decline in aging and AD. The goal of this research is to examine how psycho-social chronic stress due to experiences of racism affects the hippocampal memory system (Aim 1), and to examine an association between moderate-intensity physical activity and hippocampal function and structure (Aim 2A) comparing African American seniors with those of European ancestry. We will then investigate whether cortisol, measured in saliva, mediates, i.e. explains, the association between chronic stress and brain integrity, and whether moderate-intensity physical activity and race moderate the strength of the correlation between chronic stress and integrity of the hippocampus and of cortical regions known to be affected by AD (Aim 2B). We will address these questions with high-resolution functional and structural MRI to examine brain integrity. These neuroimaging techniques have the resolution to zoom in on the dentate gyrus subfield of the hippocampus, which is the primary area where adult neurogenesis occurs, while at the same time allowing examination of cortical AD signature regions. We will leverage the availability of an African American cohort in the Health Outreach Program for the Elderly (HOPE) registry at the Boston University Alzheimer's Disease Center. The proposed work could generate a new hypothesis: individuals experiencing chronic psychosocial stress due to racism may show accelerated cognitive decline consistent with AD. In the future this new hypothesis could then be tested by following HOPE participants longitudinally and could examine exercise training as a modulator. Reducing the AD health disparity among racial/ethnic groups in the U.S. is a critical public health goal.