Mechanisms of Executive Decline in Normal Aging

描述（由申请人提供）：本项目的总体目标是确定在衰老过程中观察到的执行功能下降背后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尚不清楚；我们需要更清楚地了解各种认知和神经变化是如何相互作用导致执行能力下降的。我们提出了一个总体模型，其中与年龄相关的额叶萎缩、额叶灌注不足和白质完整性丧失相互作用，影响信息处理速度和执行功能。我们建议对150名正常老年人进行前瞻性研究，在基线和36个月后进行结构神经成像、灌注和认知测量。我们有三个具体目的：1)横断面测试年龄、额叶结构、额叶灌注、白质和认知之间的关系；2)确定MRI和认知结果的潜在健康和生活方式预测因素；3)验证MRI纵向变化与认知纵向变化的关系。本项目利用新发展的高场、高分辨率MRI技术和认知心理学方法来测量处理速度和执行功能。我们特别关注白质的完整性，因为它可能受到生活方式和健康问题的影响，而这些问题是可以治疗的。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。对公共卫生的潜在贡献在于，这些与年龄有关的变化可能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.