权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Anatomical correlates of executive function decline in normal aging.

正常衰老过程中执行功能下降的解剖学相关性。

基本信息

批准号：
7486288
负责人：
Deborah M Little
金额：
$ 15.66万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2009-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Although many cognitive functions improve with advanced age (i.e., linguistic knowledge), declines in performance on so-called frontal lobe functions is well-documented (Kausler, 1991; Salthouse, 1985; Hasher & Zacks, 1988; West, 1996). In concert with these findings of behavioral degradations, functional neuroimaging studies commonly report changes in the magnitude and distribution of neuronal activity across networks implicated in executive functions in young and middle aged adults. The source of these age-related changes in executive function remains elusive. Two potential mechanisms for changes in neuronal activity and behavior are structural and physiological changes in the cerebrum that differentially affect the gray and white matter within the prefrontal cortex (PFC) (Haug & Eggers, 1991; Resnick et al., 2003; Tisserand et al., 2002). However, other than consistently reporting age-related declines in PFC gray and white matter volume and a decrease in white matter integrity, a review of the literature on the cognitive correlates of these anatomical changes does not delineate a clear relationship. Recent work highlights the role of white matter integrity for cognitive aging but does not differentiate between short and long range white matter fibers. The overall objective of the proposed investigation is to further define the specific mechanisms that elucidate the relationship between structure and function in normal aging. To do this we aim to (i) characterize the relationship between executive function, assessed behaviorally and with functional magnetic resonance imaging, (ii) characterize the relationship between neuronal activation and integrity of both gray and white matter volume, and finally to (iii) characterize the differential roles of small white matter fiber tracts, compared to large fiber tracts, as they relate to cognitive function in normal aging. To do this we will collect functional Magnetic Resonance Imaging (fMRI) data during performance of a verbal working memory task in a group of younger (n=15, aged 20-30), late-middle aged (n=25, aged 50-60) and super-healthy older (n=45, aged 70-80) community-dwelling adults. Four levels of difficulty will be used in the functional task so that each group of subjects will be able to attain high accuracy in one paradigm (lowest memory load) and chance performance in another paradigm (highest load). In addition to the functional data, structural MRI and diffusion tensor imaging (DTI) data will be collected and that will allow for analysis of gray matter density in PFC and calculation of white matter integrity (fractional anisotropy, FA) in the frontal lobes. Our specific aims are to characterize the relationship between executive function, measured behaviorally (accuracy, latency), and neuronal activation (signal change, volume of activation) and to characterize the relationship between neuronal response during performance of an executive function task (signal change, volume) and integrity of gray and white matter (volume) in PFC. The mechanisms that underlie the structure-function relationship in aging are poorly understood. A better understanding of these mechanisms is central to identifying basic mechanisms of cognitive aging in order to develop more targeted outcome measures in intervention studies and for investigation into the structural changes that accompany cerebrovascular risk factors. In this proposal, we present pilot data showing how the use of multiple neuroimaging modalities in a well-understood executive function paradigm narrows this structure-function question. Additionally, we propose to differentiate short from long white matter fibers to better address the relationship between white matter integrity and cognitive aging.

描述（由申请人提供）：虽然许多认知功能随着年龄的增长（即语言知识）而改善，但所谓的额叶功能的表现下降是有据可查的（Kausler，1991；Salthouse，1985；Hasher＆Zacks，1988；West，1996）。与这些行为退化的发现相一致，功能神经影像学研究通常报告与年轻人和中年人的执行功能有关的神经元活动的幅度和分布的变化。这些与年龄相关的执行功能变化的根源仍然难以捉摸。神经元活动和行为变化的两个潜在机制是大脑的结构和生理变化，这些变化对前额皮质（PFC）内的灰质和白质产生不同的影响（Haug & Eggers，1991；Resnick 等，2003；Tisserand 等，2002）。然而，除了一致报道与年龄相关的 PFC 灰质和白质体积下降以及白质完整性下降之外，对这些解剖学变化的认知相关性的文献综述并没有描绘出明确的关系。最近的工作强调了白质完整性对认知衰老的作用，但没有区分短程和长程白质纤维。拟议研究的总体目标是进一步确定阐明正常衰老中结构和功能之间关系的具体机制。为此，我们的目标是（i）表征执行功能之间的关系，通过行为和功能磁共振成像进行评估，（ii）表征神经元激活与灰质和白质体积完整性之间的关系，最后（iii）表征小白质纤维束与大纤维束相比的不同作用，因为它们与正常衰老中的认知功能相关。为此，我们将在一组年轻（n=15，20-30 岁）、中后期（n=25，50-60 岁）和超级健康老年人（n=45，70-80 岁）社区居住成年人执行言语工作记忆任务期间收集功能磁共振成像 (fMRI) 数据。功能性任务将使用四个难度级别，以便每组受试者能够在一种范式（最低记忆负载）中获得高精度，并在另一种范式（最高负载）中获得机会表现。除了功能数据外，还将收集结构 MRI 和扩散张量成像 (DTI) 数据，以便分析 PFC 中的灰质密度并计算额叶中的白质完整性（分数各向异性，FA）。我们的具体目标是表征执行功能、行为测量（准确性、潜伏期）和神经元激活（信号变化、激活量）之间的关系，并表征执行功能任务期间神经元反应（信号变化、体积）与 PFC 中灰质和白质完整性（体积）之间的关系。人们对于衰老过程中结构与功能关系的机制知之甚少。更好地理解这些机制对于确定认知衰老的基本机制至关重要，以便在干预研究中制定更有针对性的结果措施，并调查伴随脑血管危险因素的结构变化。在本提案中，我们提供了试点数据，展示了如何在易于理解的执行功能范式中使用多种神经影像模式来缩小这一结构功能问题的范围。此外，我们建议区分短白质纤维和长白质纤维，以更好地解决白质完整性和认知衰老之间的关系。