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主诉，但这个问题很难研究，因为有许多因素会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）在整个生命周期中大脑解剖学和生理学中发生的正常健康年龄相关变化，这些变化介导不同认知策略的自然展开（例如，言语中介/抽象）和2）两个病理过程（例如，高血压和2型糖尿病），通常伴随着正常衰老。一个目标是将健康的“成功”衰老与“正常”衰老分别区分开来，因为血管和代谢紊乱也会靶向前额皮质，导致认知能力下降和痴呆症（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型糖尿病可以控制或预防。出于启发性目的，衰老将从两个“传统”观点和另一个“系统”观点来考虑，传统观点认为随着年龄的增长，组织和功能储备不可避免地会丧失，而另一个“系统”观点则关注白色物质（WM）束的成熟和退化，WM束为大脑区域之间的有效沟通提供了机制。我们建议使用脑磁图或MEG检查视觉情景记忆功能，沿着扩散张量成像（DTI），MR形态测量学和神经心理学测试，以调查之间的联系：1）WM完整性和系统连接，这是必要的高级认知功能的发展;和2）WM病理和记忆性能退化。由于疾病的成熟和失活的额顶叶电路的最佳激活的演示将突出WM束有效的自上而下的策略，如口头调解/抽象的重要性。来自三个年龄组的健康参与者将被检查，以表征认知控制的发展和随之而来的成年期大脑激活模式的变化（18-25，35-45，？65年）。还将检查一组患有1）高血压和2）2型糖尿病的中年受试者，沿着一组患有高血压的老年受试者，因此产生6组，每组30个个体。脑磁图反应谱定位到特定的皮层区域和DTI/神经心理学测试结果之间的相关性的模式将有助于表征这些大脑区域的功能，而受试者从事的记忆任务。形态测量和DTI分析将提供年轻人是否仍在成熟的独立测量（在这种情况下，中年组应该表现最好，并且在前额叶皮层中具有更高的WM体积），或者是否存在灰色和WM体积和表现的线性下降（即，系统与传统的老龄化观点分别）。这个建议将证明健康的成功衰老并不一定会导致记忆功能障碍。相反，最近的证据表明，血管和代谢疾病，如高血压和2型糖尿病，靶向前额皮质，并导致认知能力下降和痴呆症，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，那么许多认知能力下降是可以预防的。

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.