The ability to perform tasks involving working memory, attention and speeded processing becomes increasingly compromised with advancing age, yet identification of the neural substrates responsible for these age related functional declines has been elusive. While structural magnetic resonance imaging (MRI) studies reveal ag-related decreases in cortical gray but not white matter volume, spectroscopic studies suggest that, despite reduced volume, gray matter integrity is not compromised in the elderly and functional imaging studies show that older subjects recruit more brain regions than their younger counterparts to execute a given task. In addition, neuropathological studies note substantial age-related changes in the microstructure of white matter (e.g., demyelination, microtubule deterioration, and axonal deletion) but not loss of neuronal number, suggesting a role for white matter as a substrate of age-related cognitive decline. With advancing age, the cortical nodes of a neural network may remain intact, but white matter interconnections of the brain system required for performance may deteriorate. Conventional MRI is not capable of detecting the age-dependent microstructural change in brain white matter observed neuropathologically. Diffusion tensor imaging (DTI) offers the unique opportunity to identify in vivo the orientation of white matter tracts and bundles and to quantify the degree of their intravoxel coherence, an index of microstructural integrity. Application of non-collinear diffusion gradients at image acquisition permits the direction of water diffusion to be determine din three dimensions and the examination of white matter tracts as they course through the brain, the directions of which are known by histology but until now could only be inferred in vivo from anatomical position on MRI. Water diffusion in healthy white matter bundles is highly anisotropic and becomes isotropic with advancing age and diseases marked by demyelination, microtubule deterioration and axonal deletion. To examine age dependent microstructural integrity of white matter brain systems and associated cognitive compromise, the investigators will combine DTI, structural MRI, and neuropsychological and electrophysiological paradigms to examine younger (age 20 to 45 years) and older (age 60 to 85 years) healthy men and women. Characterization of patterns of white matter microstructure deterioration in normal aging should lead to an understanding of the pathophysiology of normal cognitive decline and is a requisite context for interpreting such changes in neurodegenerative disease of the aged.
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