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 and cognition caused by Alzheimer's disease pathology. This project will use state of the art MRI at high field to measure changes occurring in the brains of 470 subjects with two or more scans in 260 subjects. Data will include 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 spatial normalization, segmentation, tractography, voxel based analyses and region of interest selection, to test statistically the following hypotheses cross sectionally and longitudinally (prediction of change in the outcome variable): 1.) Arteriosclerosis correlates with reduced brain perfusion, WMLs and lacunar infarcts, GM atrophy, and reduced fractional anisotropy of WM tracts, especially the superior longitudinal fasciculus and the occipital frontal tracts. 2.) White matter lesions (WMLs, especially periventricular WMLs in the frontal lobe) and lacunar infarcts correlate with reduced perfusion of frontal lobe and reduced FA of white matter tracts, especially the superior longitudinal fasciculus and occipital frontal tract. 3.) Atrophy of hippocampal subfields (a marker of AD pathology) correlates with reduced perfusion of the posterior 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 correlate with executive function while hippocampal volumes, posterior cingulate perfusion, and FA of cingulum tract correlate 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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