Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients

Abstract

A subgroup of patients with breast cancer suffers from mild cognitive impairment after chemotherapy. To uncover the neural substrate of these mental complaints, we examined cerebral white matter (WM) integrity after chemotherapy using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. Postchemotherapy breast cancer patients (n = 17) and matched healthy controls (n = 18) were recruited for DTI and neuropsychological testing, including the self-report cognitive failure questionnaire (CFQ). Differences in DTI WM integrity parameters [fractional anisotropy (FA) and mean diffusivity (MD)] between patients and healthy controls were assessed using a voxel-based two-sample-t-test. In comparison with healthy controls, the patient group demonstrated decreased FA in frontal and temporal WM tracts and increased MD in frontal WM. These differences were also confirmed when comparing this patient group with an additional control group of nonchemotherapy-treated breast cancer patients (n = 10). To address the heterogeneity observed in cognitive function after chemotherapy, we performed a voxel-based correlation analysis between FA values and individual neuropsychological test scores. Significant correlations of FA with neuropsychological tests covering the domain of attention and processing/psychomotor speed were found in temporal and parietal WM tracts. Furthermore, CFQ scores correlated negatively in frontal and parietal WM. These studies show that chemotherapy seems to affect WM integrity and that parameters derived from DTI have the required sensitivity to quantify neural changes related to chemotherapy-induced mild cognitive impairment.

Figure 1

Axial (a) and coronal (b) slices with significantly decreased FA (red) and significantly increased MD (blue) in patients that received chemotherapy versus healthy controls (P < 0.05 corrected for multiple comparisons). Regions where both effects are present are colored purple/brown. Axial (c) and coronal (d) slices with significantly decreased FA in impaired patients (red) and in unimpaired patients (green) versus healthy controls (P < 0.05 corrected for multiple comparisons). Regions where both effects are present are colored yellow/light green. Numbers (mm) define the location relative to z (a–c) and y (b–d) in MNI coordinates.

Figure 2

(a) Scatter plot of WAIS digit symbol scores and mean FA values in a cluster covering part of the superior and inferior longitudinal fasciculus. (b) Thresholded T‐map showing areas with significant positive correlation between WAIS digit symbol test score and FA values, overlaid on the mean FA image. (c) Scatter plot of nine hole pegboard test (9HPT) results and mean FA values in a cluster covering the posterior thalamic radiation. (d) Thresholded T‐map showing areas with significant negative correlation between 9HPT score and FA values, overlaid on the mean FA image. (e) Scatter plot of cognitive failure questionnaire (CQF)—distraction scores and mean FA values in resulting a cluster at the border of superior longitudinal fasciculus and external capsula. (f) Thresholded T‐map showing areas with significant negative correlation between CQF‐distraction score and FA value, overlaid on the mean FA image.