Gray matter concentration and effective connectivity changes in Alzheimer's disease: a longitudinal structural MRI study

Xingfeng LiThomas M McGinnity


Understanding disease progression in Alzheimer's disease (AD) awaits the resolution of three fundamental questions: first, can we identify the location of "seed" regions where neuropathology is first present? Some studies have suggested the medial temporal lobe while others have suggested the hippocampus. Second, are there similar atrophy rates within affected regions in AD? Third, is there evidence of causality relationships between different affected regions in AD progression? To address these questions, we conducted a longitudinal MRI study to investigate the gray matter (GM) changes in AD progression. Abnormal brain regions were localized by a standard voxel-based morphometry method, and the absolute atrophy rate in these regions was calculated using a robust regression method. Primary foci of atrophy were identified in the hippocampus and middle temporal gyrus (MTG). A model based upon the Granger causality approach was developed to investigate the cause-effect relationship over time between these regions based on GM concentration. Results show that in the earlier stages of AD, primary pathological foci are in the hippocampus and entorhinal cortex. Subsequently, atrophy appears to subsume the MTG. The causality results sho...Continue Reading


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