The purpose of this project will be to better characterize independent and interactive contributions to dementia of AD and SIVD. This project will use common, core data that is available for all subjects enrolled in the overall program project grant (PPG). It will focus on global and specific cognitive abilities and independent functioning as dependent variables and will incorporate date from longitudinal follow-up and neuropathology to address questions about additive and interactive effects of AD and SIVD in determining presentation and progression of dementia. It will develop linear measurement procedures that will be implemented within the Central Coordinating Core and will serve as the basis for evaluating effects of AD and SIVD on progression of dementia. Mechanisms of cognitive and functional change in AD and SIVD will be examined using cross sectional, longitudinal, and pathological data. Multiple replications will be accomplished by performing the same analyses using data from three sources so that convergence of findings can be directly compared. The availability of data from neuropathology will allow for a critical form of replication. Hypotheses to be tested in this project are: 1) Cognitive and functional impairment in SIVD and AD are primarily due to loss of volume of cortical gray matter and hippocampus, 1a) Effects of lacunar infarcts and abnormal white matter on cognitive and functional impairment are primarily mediated by associated loss of volume of cortical gray matter and hippocampus, 2) Predicted relationships from Hypothesis 1 will be supported in neuropathology diagnosed cases without AD and independently in pathology diagnosed cases with AD, 3) Rate of progression of cognitive impairment and dementia will be primarily determined by the rate of change in volume of cortical gray matter and hippocampus and 4) Specific cognitive abilities will be differentially predicted by localized brain changes.
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