The Relationship Between Cortical Thickness And Semantic Fluency In Clinical And Pre-Clinical Alzheimer'S Disease

OBJECTIVE: We examined the relationship between semantic fluency and cortical atrophy, to identify specific cortical regions that play a role in semantic fluency. BACKGROUND: Alzheimer9s disease is a progressive dementia characterized by declarative memory loss, language difficulties, and behavioral changes. Examining the associations between cortical atrophy and cognitive performance may help further elucidate the underpinnings of this disorder. DESIGN/METHODS: Structural magnetic resonance images (MRI) were collected from 9 Normal (NC), 40 Mild Cognitive Impairment (MCI), and 10 probable AD subjects as part of the Alzheimer9s Disease Neuroimaging Initiative (ADNI). Subjects were administered the Category Fluency (CF) animals and vegetables tests. A computational anatomy-based cortical thickness technique was applied to the MRI scans. Linear regression models were applied to detect associations between performance on the semantic fluency tests and cortical atrophy in each cerebral hemisphere. RESULTS: In the CF animals and vegetables tests, poorer semantic fluency was associated with bilateral cortical atrophy of the inferior parietal lobule (Brodmann areas (BA) 39 and 40) and BA 4 and 6 in the frontal lobe. More diffuse frontal associations were seen in the left hemisphere, involving BA 9, 10, 32, 44, 45, and 46. Additional cortical atrophy was seen in the temporoparietal (BA 37) and right peristriate (BA 19, 18) cortex. Associations were far more diffuse for the vegetable category than for the animal category. The permutation-corrected map-wise significance for CF animals was pcorrected=0.01 for the left hemisphere, and pcorrected=0.06 for the right hemisphere. The permutation-corrected map-wise significance for CF vegetables was pcorrected=0.009 for the left hemisphere, and pcorrected=0.03 for the right hemisphere. CONCLUSIONS: These results demonstrate the profound effect of cortical atrophy on semantic fluency. Specifically, our results show that cortical atrophy in the frontal and temporoparietal regions, which have been previously implicated in tapping into semantic knowledge, negatively impacts semantic fluency. Supported by: Easton Consortium for Alzheimer Drug Discovery and Biomarkers NIA R01 AG040770, NIA P50 AG16570; and The Alzheimer9s Disease Neuroimaging Initiative (ADNI) NIA U01AG024904. Disclosure: Dr. Eastman has nothing to disclose. Dr. Hwang has nothing to disclose. Dr. Lazaris has nothing to disclose. Dr. Chow has nothing to disclose. Dr. Ramirez has nothing to disclose. Dr. Babakchanian has nothing to disclose. Dr. Woo has nothing to disclose. Dr. Thompson has nothing to disclose. Dr. Apostolova has received personal compensation for activities with Eli Lilly & Company as a speaker. Dr. Apostolova has received compensation from CODA.