Effects of chemotherapy on aging white matter microstructure: A longitudinal diffusion tensor imaging study

Abstract

We aimed to use diffusion tensor imaging (DTI) to detect alterations in white matter microstructure in older patients with breast cancer receiving chemotherapy. Methods: We recruited women age ≥60 years with stage I-III breast cancer (chemotherapy [CT] group; n = 19) to undergo two study assessments: at baseline and within one month after chemotherapy. Each assessment consisted of a brain magnetic resonance imaging scan with DTI and neuropsychological (NP) testing using the National Institutes of Health (NIH) Toolbox Cognition Battery. An age-and sex-matched group of healthy controls (HC, n = 14) underwent the same assessments at matched intervals. Four DTI parameters (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) were calculated and correlated with NP testing scores. Results: For CT group but not HCs, we detected statistically significant increases in MD and RD in the genu of the corpus callosum from time point 1 to time point 2 at p b 0.01, effect size:0.3655 and 0.3173, and 95% confidence interval: from 0.1490 to 0.5821, and from 0.1554 to 0.4792, for MD and RD respectively. AD values increased for the CT group and decreased for the HC group over time, resulting in significant between-group differences (p = 0.0056, effect size:1.0215, 95% confidence interval: from 0.2773 to 1.7657). There were no significant correlations between DTI parameters and NP scores (p N 0.05). Conclusions: We identified alterations in white matter microstructures in older women with breast cancer undergoing chemotherapy. These findings may potentially serve as neuroimaging biomarkers for identifying cognitive impairment in older adults with cancer.

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] .…”

“…FA) and additional measures (i.e. mean (MD), axial, radial diffusivity) of WM microstructure [ 42 , 48 ] or iron deposition [49] and cognitive performance.…”

Measuring decline in white matter integrity after systemic treatment for breast cancer: omitting skeletonization enhances sensitivity

“…A follow-up study to Deprez et al (Billiet et al 2018) observed a return to baseline values of FA 3 to 4 years after chemotherapy, suggesting recovery of white matter integrity after initial injury. Application of a skeletonization step might also explain the absence of voxel-based decline in FA in other studies in the field of CRCI (Chen et al 2019;Correa et al 2016;Mo et al 2017).…”

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

“…Generation of new oligodendrocytes is also critical for complex motor learning (McKenzie et al , ) and spatial memory consolidation (Steadman et al , ). Imaging studies on human cancer survivors reveal a reduction in several white matter tracts (Deprez et al , , ; Chen et al , ), suggesting reduced myelination. Supporting these observations, several studies reported that oligodendrocyte precursor cells (OPCs) and non‐dividing mature oligodendrocytes are especially vulnerable to chemotherapy as compared to neurons and astrocytes (Dietrich et al , ; Han et al , ; Hyrien et al , ).…”