Briefly, the findings of this project (total of 120 subjects, divided into 6 groups of 20 each) were: 1.) Reduced N-acetyl aspartate [NAA] in cortical gray matter (cGM) and hippocampus of demented patients (D) with lacunes (+L many of whom have subcortical ischemic vascular dementia (SIVD)) compared to elderly controls (CN), similar to changes in D without lacunes (many of whom have Alzheimer's). 2) Frontal cGM [NAA] was reduced to patients with thalamic lacunes, compared to those with non thalamic L. 3) cGM [NAA] was reduced in proportion to number of L and to % white matter lesions (WML). 4) MMSE and specific neuropsychological tests correlated with cGM [NAA]. Taken together, these finding strongly support the view that cGM [NAA] is reduced in D, and that this reduction is proportional in extent and location to subcortical infarction. We interpret the reduced cGM[NAA] to indicate either injury, reduced size, or reduced number, or cortical neurons, in response to subcortical infarction. This project will extend these findings by using short TE 1H MRSI to measure myo-inositol (a putative marker of Alzheimer's disease) and by using arterial spin labeled perfusion MRI to quantitate cortical and subcortical perfusion. The sample size will be about 60 subjects/group, followed autopsy for final pathological diagnosis of Alzheimer's and/or infarction. All subjects will have MRI with segmentation and hippocampal voluming, and multi-slice short TE 1H MRSI. Other related goals are to: 1.) Determine the relative extent that NAA, myoinositol, and perfusion are altered in SIVD and AD. 2.) To determine the relative extent to which subcortical infarction and cortical neuron damage contribute to dementia. 3.) To develop antemortem classification methods which reliably distinguish between SIVD and AD. 4.) To establish reliable products of cognitive decline in SIVD and AD. This project will help determine the effects of subcortical infarction on cognition, predict the effects of subcortical infarction our cognitive decline, and help distinguish between SIVD and AD. The significance is that this work will provide new understanding concerning the pathogenesis of SIVD and AD, improve the antemortem diagnosis of both disorders, and provide methods for evaluation the results of clinical treatment trials.
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