Imaging the Development of Memory Strategies in Aging

描述(申请人提供)：记忆障碍是老年人最常见的症状，但这个问题很难研究，因为有许多因素导致与年龄有关的记忆变化。这些因素中的两个将是拟议研究的重点：1)在整个生命周期中大脑的解剖和生理发生的正常健康的年龄相关变化，这些变化调节不同认知策略的自然展开(例如，语言调解/抽象)和2)通常伴随正常衰老的两个病理过程(例如，高血压和2型糖尿病)。一个目标是将健康的“成功”衰老与“正常”衰老分别区分开来，因为血管和代谢障碍也以前额叶皮质为目标，并导致认知能力下降和痴呆症(包括阿尔茨海默病)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。出于启发式的目的，衰老将从表明随着年龄的增长组织和功能储备不可避免地丧失的“传统”观点和关注脑白质(WM)束的成熟和退化的另一种“系统”观点来考虑，白质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脑磁图来检测有或没有干扰的视觉情景记忆功能，以及扩散张量成像(DTI)、磁共振形态计量学和神经心理学测试，以探讨以下之间的联系：1)工作记忆完整性和系统连通性，这是高级认知功能发展所必需的；以及2)工作记忆病理和记忆成绩下降。在疾病导致的成熟和失活的情况下，额顶神经回路的最佳激活将突显WM束对于有效的自上而下策略的重要性，例如语言调解/抽象。来自三个年龄组的健康参与者将接受检查，以表征认知控制的发展以及成年后(18-25岁，35-45岁，65岁)大脑激活模式的变化。一组患有1)高血压和2)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被检查，从而产生6组，每组30人。定位于特定皮质区域的脑磁图反应谱与DTI/神经心理测试结果之间的相关性模式将有助于表征受试者在进行记忆任务时这些脑区的功能。形态计量学和DTI分析将为年轻人是否仍在成熟提供独立的衡量标准(在这种情况下，中年组表现最好，前额叶皮质的白质体积更高)，或者灰质和白质体积和表现是否随年龄线性下降(即，分别是系统和传统的衰老观点)。这项建议将证明，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疾病以前额叶皮质为靶点，并导致认知能力下降和痴呆症(包括阿尔茨海默病)风险增加。这项研究很重要，因为如果让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，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.