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.
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