White matter integrity is critical to cognitive functions. Using diffusion-tensor imaging (DTI), it is now possible to directly assess the pattern and severity of white matter disruption in the early stages of dementia. This proposal considers the role of white matter tracts in AD and in subcortical vascular dementia (SVD). The hypotheses will examine whether: a) SVD initially disrupts frontal-subcortical loops, whereas in AD long cortical-cortical connections incur damage later and in addition to damage to the perforant pathway, b) fronto-occipital connectivity and thalamo-frontal connectivity correlate with MRI determined volumes of hippocampii, frontal cortical gray matter, and white matter hyperintensities (WMH), and c) fronto-occipital connectivity and thalamo-frontal connectivity correlate with severity of cognitive impairment (as assessed by global cognitive ability, memory, and executive function) using hippocampal volume and apoE as covariates. A cohort of 60 subjects divided into three groups, normal controls (NC), AD and SVD will be studied. The AD group will include persons with mild amnestic-type cognitive impairment (MCI) as well as probable AD. The SVD group will include persons with vascular cognitive impairment (VCI), as well as dementia meeting criteria for probable or possible VD (vascular dementia) or mixed AD/VD. Recruitment and follow-up of subjects and quantitative MRI will use resources from the ADRC Clinical and Imaging Cores, as well as the ischemic vascular dementia (IVD) Program Project Stet. Subjects will undergo MRI and neuropsychological testing at baseline and again after an interval of two years. Structural images will be segmented for volumetric analyses of selected regions. Diffusion weighted images will be converted into fractional anisotropy maps for DTI-Tractography. Connectivity will be quantified through metrics representing a normalized count of tracts between selected regions and the distribution of fractional anisotropy along these tracts.The connectivity metrics, volumetric analyses and neuropsychological scores will be used to test the hypotheses.
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