This program project provides a unique opportunity to study, using modem neuropathologic techniques, the brains of patients with ischemic-vascular dementia (IVD) who have been followed longitudinally over years by detailed clinical, neuropsychological, and sophisticated neuroimaging examinations. Brain tissue from these individuals will be examined at necropsy utilizing rigorous, standardized neuropathologic assessment, with a focus on identifying patterns of cerebral atherosclerosis and microvascular disease (especially arterio-/arteriolosclerosis) and their role in producing focal brain lesions, regional ischemic changes within both cerebral cortex and white matter, as well as the severity of 'Alzheimerization'. Quantitative measures of both cerebrovascular disease and ischemic parenchymal lesions (CVD/IVD-path scores) will be obtained for each brain studied. Evaluation of parameters within brain that may reflect non-infarctive cortical/white matter injury using morphologic, including immunohistochemical, methods will be undertaken. Data from these examinations will be used to develop a sophisticated neuropathologic database, the contents of which will be made available to other Cores and investigative Projects within the PPG, in order to optimize correlative data using autopsy findings as one 'outcome' measure in longitudinally followed patients. We will also use the new methodology of tissue microarrays (TMAs) or tissue chips to study the neuroanatomical heterogeneity of lesions in a given brain, as well as variations among different brains examined, and provide this as a resource to Alzheimer Centers with an interest in contrasting patterns of neuropathologic change in parenchymal vs. vascular dementias.