HIPPOCAMPAL INTEGRITY AND AGING: GLUCOSE & CORTISOL EFFECTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。记忆力丧失在老年人关注的健康问题中名列前茅。大多数受影响的老年人都有记忆缺陷，这些缺陷并不直接归因于血管或退行性疾病。因此，非常需要对这些损害的其他候选机制进行概念化和测试。这项建议的目的是评估非痴呆、非糖尿病老年人外周血糖调节不良和皮质醇失调对海马体体积和记忆表现的影响。海马区的结构将通过MRI得出的体积来评估，其功能将通过陈述性记忆评估来评估。据信，葡萄糖调节不良或皮质醇调节失调的个体将会出现特定的海马体体积减少，这将与陈述性记忆表现的特定损害有关。有强有力的初步数据表明，这些假设的横截面关系是可行的。此外，研究人员假设，这将是一个累积效应；血糖调节不良和皮质醇调节失调的个体将受到更大的影响。研究人员还预测，葡萄糖调节的纵向下降或皮质醇失调的增加将使老年人面临更大的海马体结构和功能丧失的风险。老年女性比男性更有可能出现皮质醇反馈抑制的改变，对皮质醇水平升高的易感性增加，并表现出更严重的与年龄相关的海马区萎缩。因此，将在假设的关系中具体考察性别的影响。我们将研究非痴呆症范围内所有认知表现的个体。研究人员希望评估120名志愿者，年龄在60岁到75岁之间，其中50%是女性，以便在两年内假设流失率为30%的情况下，每个性别组都有超过40名受试者。研究人员已经开发出有效和可靠的基于MRI的海马区测量方法，并在与拟议研究的人群一起工作方面有着悠久的历史。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Memory loss ranks high among the health issues that concern senior citizens. Most of the elderly affected have memory deficits that are not directly attributable to vascular or degenerative disorders. Hence, there is a great need to conceptualize and test other candidate mechanisms for these impairments. The goal of this proposal is to assess, among non-demented, non-diabetic elderly, the impact of poor peripheral glucose regulation and cortisol dysregulation on hippocampal volume and memory performance. Hippocampal structure will be assessed by means of MRI-derived volumes and its function by declarative memory assessments. It is believed that individuals with poor glucose regulation or cortisol dysregulation will have specific reductions in hippocampal volumes that will be associated with specific impairments in declarative memory performance. There is strong preliminary data pointing to the feasibility of these hypothesized cross-sectional relationships. In addition, the investigators hypothesize that there will be a cumulative effect; individuals with both poor glucose regulation and cortisol dysregulation will be more affected. The investigators also predict that longitudinal declines in glucose regulation or increases in cortisol dysregulation will place elderly individuals at risk for larger losses in hippocampal structure and function. Older women are more likely than men to have alterations in cortisol feedback inhibition, to have increased vulnerability to elevated cortisol levels, and to show stronger age-related hippocampal atrophy. Consequently, the impact of gender will be specifically examined in the hypothesized relationships. Individuals spanning the whole range of cognitive performance in the non-demented range will be studied. The investigators hope to assess 120 volunteers, 60 to 75 years of age and 50% female so as to have over 40 subjects in each gender group at follow-up, assuming a 30% attrition rate at the two year follow-up. The investigators have developed valid and reliable MRI-based hippocampal measurement methods and have a long history of working with the population proposed for study.