Psychosocial stressors and the hippocampal memory system in African American seniors

项目摘要/摘要 非裔美国人患阿尔茨海默氏症的比例高于欧洲血统的美国人 (Ad)。造成这种健康差距的根本原因还没有得到很好的理解。非裔美国高年级学生表演 在一系列认知测试中，他们比白人老年人还差。社会经济和健康状况的差异说明 对于这种差距的很大一部分来说，但分歧仍然存在。虽然种族没有生物学基础，但歧视 在非裔美国人中，与少数族裔地位相关的是一种突出的慢性心理社会应激源，对健康产生负面影响，导致肥胖、高血压和其他疾病。这表明，由于种族主义经历造成的心理社会慢性压力可能导致AD和认知方面的健康差异。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， 受到阿尔茨海默病和慢性压力的负面影响。应激模型显示，成年大脑中新神经元的生成--海马区神经发生的速度受到负面影响。 由于慢性压力、衰老和阿尔茨海默病。此外，海马体和内嗅觉皮质有很高的浓度 糖皮质激素受体，这是“应激激素”皮质醇的结合部位。另一个久负盛名 有氧运动是成人神经发生的调节器。有氧运动和慢性压力都很有效，但 成人神经发生的相反调节剂。增加体力活动是减缓衰老和阿尔茨海默病认知衰退的最有效的干预措施之一。这项研究的目的是研究种族主义经历引起的心理社会慢性压力如何影响海马体记忆系统(目标1)，并研究中等强度体力活动与海马体功能和结构之间的联系。 (目标2A)比较非裔美国老年人和欧洲血统的老年人。然后我们将进行调查 唾液中的皮质醇是否调节，即解释慢性应激与大脑之间的联系 正直，以及中等强度的体力活动和种族是否缓和强度的相关性 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 (目标2B)。我们将用高分辨率的功能和结构磁共振成像来检查大脑来解决这些问题 正直。这些神经成像技术具有放大大脑皮质齿状回亚区的分辨率 海马区，这是成人神经发生的主要区域，同时允许检查皮质AD标志区。我们将利用非洲裔美国人队列在 老年人健康外展计划(HOPE)在波士顿大学阿尔茨海默病中心登记。 这项拟议的工作可能会产生一个新的假设：经历慢性心理社会压力的人 对种族主义的反应可能表现出与AD相一致的认知加速衰退。在未来，这一新的假设可能 然后通过纵向跟踪HOPE参与者进行测试，并可以将运动训练作为一个调节器进行检验。减少美国种族/民族之间的AD健康差距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.