The overall goals of this project are 1) to determine the extent to which arteriosclerosis (measured by C-IMT,R-AV ratio) is associated with changes of brain perfusion, and the volume and integrity of gray matter (GM)and white matter (WM) and 2) the extent to which this association relates to the changes in brain andcognition caused by Alzheimer's disease pathology. This project will use state of the art MRI at high field tomeasure changes occurring in the brains of 470 subjects with two or more scans in 260 subjects. Data willinclude structural MRI to measure gray matter and white matter lesions (WMLs), hippocampal subfields,arterial spin labeled perfusion (ASL) MRI to quantify cerebral blood flow, and diffusion tensor imaging (DTI)to quantify measures of integrity of white matter tracts. Image analysis will use: registration and spatialnormalization, segmentation, tractography, voxel based analyses and region of interest selection, to teststatistically the following hypotheses cross sectionally and longitudinally (prediction of change in theoutcome variable):1.) Arteriosclerosis correlates with reduced brain perfusion, WMLs and lacunar infarcts, GM atrophy, andreduced fractional anisotropy of WM tracts, especially the superior longitudinal fasciculus and the occipitalfrontal tracts.2.) White matter lesions (WMLs, especially periventricular WMLs in the frontal lobe) and lacunar infarctscorrelate with reduced perfusion of frontal lobe and reduced FA of white matter tracts, especially the superiorlongitudinal fasciculus and occipital frontal tract.3.) Atrophy of hippocampal subfields (a marker of AD pathology) correlates with reduced perfusion of theposterior cingulate GM and reduced FA of the cingulum tract WM.4.) Regions of: frontal lobe perfusion, FA of frontal lobe white matter, and volume frontal lobe GM correlatewith executive function while hippocampal volumes, posterior cingulate perfusion, and FA of cingulum tractcorrelate with memory function.Finally, we will explore the relationship of PIB uptake (amyloid load), and FDG uptake, to the structural,perfusion, and DTI changes detected by MRI.
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