Mechanisms of Executive Decline in Normal Aging

描述(由申请人提供)：本项目的首要目标是确定在衰老过程中观察到的执行功能下降的认知机制和神经结构。包括我们在内的几个研究小组已经记录了与年龄相关的执行功能下降及其对日常功能的重大影响。然而，这种下降的根本原因仍然不清楚；我们需要更清楚地理解各种认知和神经变化是如何相互作用，从而产生高管下降的。我们提出了一个总体模型，在这个模型中，与年龄相关的额叶萎缩、额叶低灌注和白质完整性的丧失相互作用，影响信息处理速度和执行功能。我们建议前瞻性地研究150名正常老年人，在基线和36个月后再次进行结构性神经成像、灌注和认知测量。我们有三个具体的目标：1)横断面测试年龄、额叶结构、额叶血流灌注、白质和认知之间的关系；2)找出潜在的健康和生活方式预测MRI和认知结果的因素；3)测试MRI纵向变化和认知纵向变化之间的关系。这个项目利用了新开发的高场、高分辨率磁共振成像技术和测量处理速度和执行功能的认知心理学方法。我们特别关注白质完整性，因为它可能会受到生活方式和健康问题的影响，这些问题可能是潜在的可以治疗的。公共卫生相关性：该项目将研究与正常衰老相关的神经和认知变化如何影响功能能力和生活质量。对公众健康的潜在贡献在于，这些与年龄相关的变化中的一些可能会受到身体健康和生活方式选择改善的影响。

DESCRIPTION (provided by applicant): The overarching goal of this project is to identify the cognitive mechanisms and neural structures that underlie the decline in executive functioning observed in aging. Several research groups, including ours, have documented age-associated decline in executive functioning and its significant impact on daily functioning. The underlying causes of this decline remain unclear, however; a clearer understanding of how various cognitive and neural changes interact to produce executive decline is needed. We propose an overarching model in which age-associated frontal atrophy, frontal hypoperfusion, and loss of white matter integrity interact to affect information processing speed and executive function. We propose to prospectively study 150 normal elderly with structural neuroimaging, perfusion, and cognitive measures at baseline and again after 36 months. We have three specific aims: 1) test the relationships between age, frontal lobe structure, frontal perfusion, white matter, and cognition cross-sectionally; 2) identify potential health and lifestyle predictors of MRI and cognitive outcomes; and 3) test the relationships between longitudinal change in MRI and longitudinal changes in cognition. This project takes advantage of newly developed techniques of high field, high resolution MRI and cognitive psychology methods of measuring processing speed and executive functioning. We are particularly focusing on white matter integrity because it may be influenced by lifestyle and health issues that are potentially treatable. PUBLIC HEALTH RELEVANCE: This project will study how interrelated neurological and cognitive changes associated with normal aging impact functional abilities and quality of life. The potential contribution to public health lies in the fact that some of these age-related changes might be influenced by improvements in physical health and lifestyle choices.