SUBCORTICAL INFARCTION, CORTICAL METABOLISM, AND DEMENTIA

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Dementia in patients with stroke is a common but heterogeneous condition that is often difficult to diagnose and pathophysiologically obscure. This project seeks to clarify the mechanisms through which subcortical lacunar infarction may lead to cognitive impairment and dementia by using magnetic resonance imaging (MRI) to quantify features of lacunes, high resolution positron emission tomography (PET) to measure cerebral metabolic rates for glucose (CMRgic) and neuropsychological tests. In order to deal with the potentially problematical heterogeneity of this population, it will use a relatively large sample of demented stroke patients, and restrict its focus to cases without evidence of cortical infarction. A total of 105 subjects, 45 SIVD patients, and 20 each of non-demented, normal controls, non-demented lacunar infarction patients, and Alzheimer's disease patients. The major variables are 1) rCMRgic as measured by a high resolution multislice PET scanner, 2) size, number, and location of lacunes as measured by quantitative magnetic resonance imaging, and 3) neuropsychological measures of rate of forgetting, associative semantic priming, attention, and abstract reasoning. The data will be analyzed with respect to 5 specific aims: 1. To test the hypothesis that subcortical lacunar infarcts which produce dementia are associated with generalized cortical hypometabolism. 2. To study lacunes as predictors of cortical hypometabolism and dementia. The relation of location, size, and number of lacunes to cortical CMRglc and dementia will be studied. It is hypothesized that cortical CMRgic is most likely to be diminished and that dementia is likely to be present with infarction of critical subcortical frontal circuits, and that lesions of the dominant hemisphere are more consequential that those of the non-dominant hemisphere. 3. To study the relationship between regional CMRgic (rCMRgic) and dementia associated with subcortical infarction. It is hypothesized that the risk of dementia is elevated in the presence of three specific patterns of rCMRgic. 4. To test the hypothesis that three specific patterns of neuropsychological impairments can be identified in dementia with subcortical lacunes. 5. To test, in conjunction with the allied project '31P and 1H Spectroscopic Imaging of Subcortical Ischemic Vascular Dementia and Alzheimer's Disease' (Project 2, PI M. Weiner), the hypothesis that reduced metabolism in SIVD is the result of deafferentatioin but not of neuronal drop out by measureing both cortical N-acetyl-aspartate (a putative marker of neuronal density) and rCMRgic in a shared sample.