Diminished gray matter density mediates chemotherapy dosage-related cognitive impairment in breast cancer patients

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.

Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy: A systematic review

“…Pre-treatment effects were found for volumetric assessments, with GM density in the frontal, temporal and occipital lobe being positively associated with both processing speed and memory [41] , while no baseline association was found with diffusion tensor imaging (DTI) [42] . In the one study examining associations during chemotherapy, changes in GM density in the frontal gyrus were positively associated with changes in executive functioning [43] .…”

“…A positive association was found between GM density in the frontal gyrus and executive functioning [55] . Additionally, self-reported global cognitive functioning was positively associated with WM metrics (FA) in frontal and parietal tracts [ 46 , 56 ], as well as in the corona radiata, the cingulate gyrus and the corpus callosum [43] . Lastly, a negative association between glucose metabolism in the frontal and temporal cortex and memory functioning was found [24] .…”

The association of genetic polymorphisms with neuroconnectivity in breast cancer patients

“…Connectome analysis is the mathematical representation on the brain's functional and structural networks. It provides insight into brain circuitry, including the integration and segregation of networks [18][19][20][21] . Functional connectome organization in this cohort of chemotherapy-treated breast cancer survivors compared to healthy female controls was previously evaluated, with decreased clustering as well as alterations of nodal degree in frontal, striatal and temporal areas being observed 22 .…”

Cortical thinning and altered functional brain coherence in survivors of childhood sarcoma

“…To date, these studies merely included adult cancer populations. Decreased GM volumes and densities were reported in adult patients with breast cancer (Blommaert et al, 2019;Conroy et al, 2013;De Ruiter et al, 2012;Feng et al, 2019;Koppelmans et al, 2012;Lepage et al, 2014;Li et al, 2018;McDonald et al, , 2010, ovarian cancer (Correa et al, 2016), testicular cancer (Amidi et al, 2016) and lung cancer (Pohler, 1992) after chemotherapy. Such differences appeared distributed across the brain (e.g.…”