This project addresses four major areas of inquiry in subcortical ischemic vascular dementia (SVID): the role of ongoing subcortical ischemia; the role of infarction and neuron loss; the role of disconnection of subcortical and cortical structures in the pathogenesis of SIVD; and the relative differences in subcortical and cortical changes between SIVD and Alzheimer's Disease (AD). We will use 31P magnetic resonance spectroscopic imaging (31p MRSI) to detect high energy phosphate metabolites as measures of ongoing ischemia. 1H MRSI to detect NAA as a measure of neuron density, and rCMRglc/NAA (in conjuction with Project 1 - Bruce Reed, Ph.D., P.I.) as a measure of the metabolic rate of viable neurons. Studies will be performed on the following groups: Group A: 50 demented subjects with subcortical lacunar infarcts (SIVD); Group B: 50 non-demented control subjects with lacunar infarcts; Group C: 50 non-demented control subjects without lacunar infarcts; Group D: 50 demented subjects without lacunar infarcts (AD). To determine the extent of ongoing ischemia in SIVD, we will test the hypothesis that: high energy phosphate ratios (Par/Pi, etc) are lower in subcortical white and grey matter in SIVD compared to controls and that these reductions are related to the extent of WMSH and lacunae. To determine the extent of neuron loss in SIVD, we will test the hypothesis that: NAA is lower in subcortical white and grey matter in SIVD compared to controls and that these reductions are related to the extent of SMSH and lacunae. To determine the extent of subcortical-cortical disconnection, we will test the hypothesis that: cortical function (neuropsychological measures and cortical rCMRglc/NAA) is reduced in proportion to subcortical energy phosphate ratios, NAA, WMSH, and lacunae in SIVD and in controls with and without lacunes. To determine severity of subcortical and cortical disease in SIVD versus AD, we will test the hypothesis that: subcortical energy phosphates and NAA and cortical rCMRglc/NAA are lower in SIVD than in AD. This project will provide a greater understanding of the pathogenesis of dementia in patients with cerebrovascular disease and AD, and will improve the antemortem diagnosis of both disorders.
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