Abstract
To investigate chemotherapy dosage-related cognitive impairment and its neural mechanisms in breast cancer (BC) patients. Twenty-eight breast cancer patients after each chemotherapy cycle and matched 29 healthy control subjects underwent structural magnetic resonance imaging. Voxel-based morphometry analysis was performed to compare group differences in the gray matter for the whole brain. Furthermore, mediation analysis was conducted to explore the role of brain structures in chemotherapy dosage-related cognitive impairment. Voxel-based morphometry analysis was performed in gray matter for the whole brain of BC patients after chemotherapy. The results revealed that the gray matter density in the left inferior frontal gyrus, right middle frontal gyrus, right fusiform area, and bilateral cerebellum was decreased in the BC patients compared to controls. The number of chemotherapy cycles was negatively associated with general cognitive capacity, verbal fluency and digit span performance in the BC patients. In addition, decreased gray matter density in the right middle frontal gyrus could mediate the chemotherapy dosage effects on verbal fluency performance. These findings indicate that the dose-response relationship between chemotherapy and cognitive impairment may depend on the decreases in gray matter density of the frontal cortical structures.
Highlights
Chemotherapy-related cognitive impairment has been reported in many studies of breast cancer patients
There were three main findings: [1] breast cancer patients undergoing chemotherapy demonstrated cognitive impairment, and the number of chemotherapy cycles was negatively correlated with cognitive performance in the patients; [2] breast cancer patients showed decreased gray matter density in the frontal gyrus, fusiform area and cerebellum; [3] the decreased gray matter density in the right middle frontal gyrus (MFG) mediated the chemotherapy dosage-related impairment in executive function in breast cancer patients
Consistent with previous studies, we showed that general cognitive capacity, working memory, and executive function were linearly correlated with the number of chemotherapy cycles, in support of a dosage effect of chemotherapy on cognitive impairment in breast cancer patients8,9
Summary
Chemotherapy-related cognitive impairment has been reported in many studies of breast cancer patients (for a review). Numerous neuroimaging studies have reported alterations in brain structure and function following chemotherapy in cancer patients. Numerous neuroimaging studies have reported alterations in brain structure and function following chemotherapy in cancer patients9 Both structural and functional brain changes have been found to be related to chemotherapy-related cognitive impairment in breast cancer patients. We aimed to investigate the chemotherapy dosage-related cognitive impairment and mediating roles of cerebral structural changes in this relationship in breast cancer patients. We hypothesized that the GM volumes in the frontal and temporal cortex and the cerebellum were decreased in the CC group and that altered GM volumes mediated the dosage-related cognitive impairment in the patients
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