Structural and Functional Brain Alterations in Post-Chemotherapy Cognitive Impairment in Gastric Cancer: A Longitudinal Multimodal Neuroimaging Study

Abstract Backgrounds: Despite clinical significance of chemobrain, no longitudinal study has been made on change in cognitive function related to chemotherapy in gastric cancer. The aim of this study is to define structural and functional changes in brains of gastric cancer patients caused by chemotherapy-induced cognitive impairment after adjuvant chemotherapy. Methods: 13 gastric cancer patients with adjuvant chemotherapy (CTx+ group), 9 gastric patients without adjuvant chemotherapy (CTx- group), and 10 healthy controls (HC) were enrolled for this study. We performed self-report questionnaires, neurocognitive tests, voxel-based morphometry (VBM), hippocampus-seeded resting-state functional magnetic resonance imaging (rsfMRI) and diffusion tensor imaging (DTI) analysis twice at before and 3 months after chemotherapy. Results: Compared to CTx- group, CTx+ group exhibited statistically significant decrease in attention and executive function over time, and also exhibited dysfunction in delayed recognition performance. Results in resting state functional connectivity analysis show significant group-by-time interaction in left hippocampus-anterior thalamus. In addition, DTI analysis had interesting results that showed reduced fractional anisotropy (FA), and increased mean diffusivity (MD) in left hippocampus. However, results from VBM analysis confirms that chemotherapy does not cause structural changes in brain. Conclusion: To the best of our knowledge, this is the first longitudinal neuroimaging study on the effect of chemotherapy in gastric cancer patients. Based on the results of this study, we suggest that neuropathological processes and clinical presentation of chemobrain is ultimately similar disease as age-related neurodegenerative disorder. Results of this study help in viewing underlying basis of chemobrain at a new angle and puts emphasis in importance of continuous assessment and intervention.