The purpose of this project is to better characterize independent and interactive contributions to dementia of AD and sCVD. 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 sCVD in determining presentation and progression of dementia. Mechanisms of cognitive and functional change in AD and sCVD will be examined using cross sectional, longitudinal, and pathological data. Multiple replications wilt be accomplished by performing the same analyses using data from these three sources so that convergence of timings 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 sCVD and AD are primarily due to loss of volume of cortical gray matter and hippocampus, 1a) Memory is primarily related to hippocampal volume and executive function to frontal cortical gray matter volume, 1b) Predicted relationships from Hypothesis 1 will be supported in neuropathology diagnosed cases without AD and independently in pathology diagnosed cases with AD, 2) sCVD and AD neuropathology measures and MRI markers of these pathologies will make additive and independent contributions to cognitive impairment and dementia, and 3) Progression to dementia in non-demented cases at initial evaluation will be strongly predicted by MRI markers of AD pathology and weakly predicted by markers of sCVD pathology.
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