Multimodal MRI and cognitive function in patients with breast cancer prior to adjuvant treatment — The role of fatigue

Abstract

An increasing body of literature indicates that chemotherapy (ChT) for breast cancer (BC) is associated with adverse effects on the brain. Recent research suggests that cognitive and brain function in patients with BC may already be compromised before the start of chemotherapy. This is the first study combining neuropsychological testing, patient-reported outcomes, and multimodal magnetic resonance imaging (MRI) to examine pretreatment cognition and various aspects of brain function and structure in a large sample.Thirty-two patients with BC scheduled to receive ChT (pre-ChT+), 33 patients with BC not indicated to undergo ChT (pre-ChT−), and 38 no-cancer controls (NCs) were included. The examination consisted of a neuropsychological test battery, self-reported aspects of psychosocial functioning, and multimodal MRI.Patients with BC reported worse scores on several aspects of quality of life, such as higher levels of fatigue and stress. However, cortisol levels were not elevated in the patient groups compared to the control group. Overall cognitive performance was lower in the pre-ChT+ and the pre-ChT− groups compared to NC. Further, patients demonstrated prefrontal hyperactivation with increasing task difficulty on a planning task compared to NC, but not during a memory task. White matter integrity was lower in both patient groups. No differences in regional brain volume and brain metabolites were found. The cognitive and imaging data converged to show that symptoms of fatigue were associated with the observed abnormalities; the observed differences were no longer significant when fatigue was accounted for.This study suggests that cancer-related psychological or biological processes may adversely impact cognitive functioning and associated aspects of brain structure and function before the start of adjuvant treatment. Our findings stress the importance to further explore the processes underlying the expression of fatigue and to study whether it has a contributory role in subsequent treatment-related cognitive decline.

Fatigue is associated with inflammation in patients with head and neck cancer before and after intensity-modulated radiation therapy

“…The basal ganglia are associated with a variety of functions such as motivation to action and motor activity (Stocco et al, 2010; Arsalidou et al, 2013). Recent studies on patients with chronic fatigue syndrome, multiple sclerosis, and breast cancer have shown that fatigue is associated with dysfunction of certain brain regions including basal ganglia (Menning et al, 2015; Miller et al, 2014; Hanken et al, 2014). Moreover, malignant melanoma patients treated with the inflammatory cytokine, interferon-alpha, were found to exhibit alterations in basal ganglia glucose metabolism as well as dopamine function, which were related to fatigue (Capuron et al, 2007).…”

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

“…Only the brain metrics and cognitive tests that were significantly different between groups were examined. To reduce the number of comparisons, a composite of the significant cognitive test scores was computed using the Mahalanobis distance, which was then log transformed (Mahalanobis, 1936; Menning et al., 2015; Stouten‐Kemperman et al., 2015). …”

“…Several cross‐sectional and longitudinal studies have demonstrated abnormalities in brain structure and function, particularly in chemotherapy‐treated patients and survivors (D'Agata et al., 2013; Deprez et al., 2014; Jung et al., 2016; Kesler & Blayney, 2015; Lepage et al., 2014; Nudelman et al., 2014; Simo et al., 2015; Stouten‐Kemperman et al., 2014). However, many patients demonstrate differences in brain structure and function prior to chemotherapy suggesting that cancer pathogenesis, surgery/anesthesia, disease burden, host‐related, and/or other factors may contribute to early brain changes (Cimprich et al., 2010; McDonald, Conroy, Ahles, West, & Saykin, 2012; Menning et al., 2015; Sato et al., 2015; Scherling, Collins, Mackenzie, Bielajew, & Smith, 2012; Scherling, Collins, Mackenzie, Lepage, et al., 2012). …”

Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial

“…Cancer-related fatigue (CRF) is conceptualized as a complex, multidimensional experience of reduced energy and increased need for rest that is not related to activity or relieved by sleep [2]. Post-treatment fatigue has been shown to negatively affect cognitive function [3], psychological well-being [4], and physical function [5]; reduce overall health-related quality of life [6]; and possibly influence survival rates [7]. Unfortunately, CRF is also one of the most persistent consequences of cancer treatment.…”