Imaging the Development of Memory Strategies in Aging

描述（由申请人提供）：记忆功能障碍是老年人最常见的抱怨，但这个问题很难研究，因为有许多因素导致与年龄相关的记忆变化。其中两个因素将是拟议研究的重点：1)在整个生命周期中发生的正常健康的与年龄相关的大脑解剖和生理变化，这些变化介导了不同认知策略的自然展开（例如，言语调解/抽象）；2)通常伴随正常衰老的两种病理过程（例如，高血压和2型糖尿病）。其中一个目标是分别将健康的“成功”衰老与“正常”衰老区分开来，因为血管和代谢紊乱也会针对前额皮质，导致认知能力下降和痴呆（包括阿尔茨海默病）的风险增加。这一点很重要，因为高血压和2型糖尿病是可以控制或预防的。出于启发式目的，衰老将从“传统”观点和另一种“系统”观点来考虑，前者认为随着年龄的增长，组织和功能储备的损失是不可避免的，后者关注的是白质束的成熟和退化，白质束为大脑区域之间的有效交流提供了机制。我们建议使用脑磁图或MEG来检查有或没有干扰的视觉情景记忆功能，以及弥散张量成像（DTI）， MR形态测量和神经心理学测试来研究：1)WM完整性和系统连接性之间的联系，这是发展高级认知功能所必需的；2) WM病理与记忆性能下降。额顶叶回路在成熟和因疾病而失活时的最佳激活，将突出WM束对有效的自上而下策略（如口头调解/抽象）的重要性。将对来自三个年龄组的健康参与者进行检查，以描述成年期认知控制的发展和随之而来的大脑激活模式的变化（18-25岁，35-45岁，15岁）。65年)。一组患有1)高血压和2)型糖尿病的中年受试者，以及一组患有高血压的老年人，也将进行检查，共分为6组，每组30人。脑皮层特定区域的脑磁图反应特征与DTI/神经心理学测试结果之间的相关模式将有助于表征受试者从事记忆任务时这些大脑区域的功能。形态计量学和DTI分析将提供独立的测量方法，以确定年轻人是否仍在成熟（在这种情况下，中年人应该表现最好，前额叶皮层的WM容量更高），或者随着年龄的增长，灰质和WM容量和表现是否呈线性下降（即，系统与传统的衰老观点分别）。这一建议将证明健康成功的衰老并不一定会导致记忆功能障碍。相反，最近的证据表明，高血压和2型糖尿病等血管和代谢紊乱以前额皮质为目标，导致认知能力下降和痴呆（包括阿尔茨海默病）的风险增加。这项研究很重要，因为如果美国人意识到良好的身体健康有助于降低晚年患痴呆症的风险，就可以预防许多认知能力下降。

DESCRIPTION (provided by applicant): Memory dysfunction is the most common complaint of the elderly but this problem is difficult to study since there are a number of factors contributing to age-related changes in memory. Two of these factors will be the focus of the proposed studies: 1) normal healthy age-related changes that occur in the anatomy and physiology of the brain throughout the life span that mediate the natural unfolding of different cognitive strategies (e.g., verbal mediation/abstraction) and 2) two pathological processes (e.g., hypertension and type 2 diabetes) that often accompany normal aging. One goal is to separate healthy "successful" aging from "normal" aging, respectively, since vascular and metabolic disorders also target prefrontal cortex and result in increased risk for cognitive decline and dementia, including Alzheimer's disease. This is important since hypertension and type 2 diabetes can be controlled or prevented. For heuristic purposes, aging will be considered from both a "traditional" view which suggests there is an inevitable loss of tissues and functional reserves across age and an alternative "systems" view that focuses on the maturation and degeneration of white matter (WM) tracts, which provide the mechanism for efficient communication between brain regions. We propose to use magnetoencephalography or MEG to examine visual episodic memory function with and without distracters, along with diffusion tensor imaging (DTI), MR morphometry, and neuropsychological tests to investigate links between: 1) WM integrity and system connectivity which are necessary for the development of higher cognitive functions; and 2) WM pathology and memory performance degradation. A demonstration of optimal activation of frontoparietal circuits with maturation and inactivation due to disease will highlight the importance of WM tracts for effective top-down strategies such as verbal mediation/abstraction. Healthy participants from three age groups will be examined to characterize the development of cognitive control and consequent changes in brain activation patterns in adulthood (18-25, 35-45, ? 65 years). A group of middle-aged subjects with 1) hypertension and 2) type 2 diabetes, along with a group of elderly with hypertension will also be examined, thus resulting in 6 groups of 30 individuals each. The patterns of correlations witnessed between MEG response profiles localized to specific cortical regions and DTI/neuropsychological test results will help characterize the functions of these brain regions while subjects were engaged in the memory tasks. Morphometric and DTI analyses will provide independent measures of whether the young are still maturing (in which case the middle-aged group should perform best and have higher WM volumes in prefrontal cortex) or whether there is a linear decline in gray and WM volumes and performance across age (i.e., systems vs traditional views of aging, respectively). This proposal will demonstrate that healthy successful aging does not necessarily lead to memory dysfunction. Instead, recent evidence indicates that vascular and metabolic disorders such as hypertension and type 2 diabetes target prefrontal cortex and result in increased risk for cognitive decline and dementia, including Alzheimer's disease. This research is important because much cognitive decline can be prevented if Americans are made aware that good physical health can help reduce the risk of developing dementia later in life.