Age-dependent brain volume and neuropsychological changes after chemotherapy in breast cancer patients

Abstract

This study investigated volumetric brain changes and cognitive performance in premenopausal and postmenopausal patients treated for early-stage breast cancer. Participants underwent elaborate neurocognitive assessments (neuropsychological testing, cognitive failure questionnaire, and high-resolution T1-weighted structural MRI) before and after chemotherapy. Volumetric brain changes were estimated, using longitudinal deformation-based morphometry, and correlated with cognitive changes. In total, 180 women participated in this study, of whom 72 patients with breast cancer had received adjuvant chemotherapy (C+), 49 patients did not receive chemotherapy (C-), and 59 healthy controls (HC). The population was categorized into two age groups: A young group who were premenopausal and younger than 52 years at baseline (n = 55C+/32C-/41HC), and an older group who were postmenopausal and older than 60 years (n = 17C+/17C-/18HC). Cognitive impairment occurred after chemotherapy in both young and older patients, although older patients showed more decline in processing speed (Trail making test b). White matter volume expansion was observed after chemotherapy, only significantly present in the younger subgroup of patients. In patients not treated with chemotherapy, diffuse gray and white matter volume reduction was observed. Less white matter expansion concurred with more cognitive decline (r > .349, p < .05). In conclusion, we found age-dependent cognitive decline and white matter volume changes in patients with breast cancer after chemotherapy, which could possibly be linked to neuroinflammatory processes. White matter expansion after chemotherapy, more pronounced in premenopausal patients, correlated with less cognitive decline. This suggests such expansion to be age-dependent, possibly caused by a protective response in the younger brain to chemotherapy-induced neurotoxicity.

Keywords: age; brain volume; cancer; chemobrain; chemotherapy; cognition; deformation-based morphometry; longitudinal; menopause; quality of life.

Figure 1

Within‐group volumetric changes of all groups, independent of age, comparing time point t2 with baseline. Brain volume changes were found in both cancer groups (C+: n = 70, C−: n = 45). No effects were found in the healthy control group (HC: n = 49). Statistical maps of volume increase and decrease are thresholded at p < .05, FWE corrected at cluster level, and color‐coded according to t‐value. See Table A2 on statistical values and MNI‐coordinates of significant clusters. C+, patients with breast cancer who underwent chemotherapy; C−, with patients with breast cancer who did not undergo chemotherapy; HC, healthy controls [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Comparison of the volumetric changes in young and old women after cancer therapy. Changes are shown for C+ (Row 1, a–c) and C− (Row 2, d–f) patients. The first (a, d with n = 53,3) and second (b, e with n = 17,14) column show regions of significant volume increase and decrease over time for the different young (premenopausal) and old (postmenopausal) groups, respectively. The last column (c, f) show regions with a significant time‐by‐age interaction effect for each group. All statistical maps are thresholded at p < .05, FWE corrected at cluster level, and color‐coded according to t‐value. See Table A3 for statistical values and MNI‐coordinates of significant clusters. C+, patients with breast cancer who underwent chemotherapy; C−, patients with breast cancer who did not undergo chemotherapy [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Correlation of changes in cognitive scores with changes in brain volume of young and old C+ patients. (a, b) Scatter plots of percental longitudinal change in left corona radiate brain volume and WAIS letter‐number sequencing change score in young patients (a) and AVLT learning in old patients (b). (c) Scatter plot of percental longitudinal change in left SLF volume and WAIS letter‐number sequencing change score in young patients. Change scores were calculated as t2 score − t1 score. For the percental volume change, these scores were divided by the baseline volume. A higher change score on the WAIS letter‐number sequencing and AVLT test indicate better performance. Positive brain volume change indicates volume expansion, while negative values indicate decrease in brain volume. AVLT, Auditory Verbal Learning Test, C+, patients with breast cancer who underwent chemotherapy; SLF, superior longitudinal fasciculus; WAIS, Wechsler Adult Intelligence Scale