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.

Prevalence of leukoencephalopathy and its potential cognitive sequelae in cancer patients

“…biomarkers of oxidative stress and inflammation), which also affects the severity of white matter changes 30 . In addition, older age at treatment is an additional risk factor in adult (breast) cancer patients, given the decreased neural integrity and cognitive reserves 58,59 . To which extent these mechanisms play a role in specific oncological populations or treatments, remains inconclusive.…”

“…Unfortunately, the longterm impact of chemotherapy-induced leukoencephalopathy on the development of neurodegenerative diseases at an older age is under-investigated. For adult cancer survivors, a subgroup of elder solid tumor survivors consistently reported difficulties in daily life due to a change in cognitive functioning after treatment for cancer 9,59,63 . How this is associated with the presence of leukoencephalopathy, remains to be unraveled in future research.…”

“…For example, multiple studies investigating the so-called "chemobrain" in cancer patients report cognitive decline after treatment with chemotherapy to co-exist with white matter differences (e.g. based on diffusion, myelin water and structural imaging), but did not necessarily look at the presence of white matter lesions 21,59,67,68 .…”

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.…”

“…Furthermore, we addressed the possible association with doses of chemotherapeutic agents and psychological (self-reported distress-related and neurocognitive) outcomes. Based on previous studies, we hypothesized that anatomical differences could be related to different chemotherapy doses (Seigers et al, 2008;Sugimoto et al, 1995) and to age at diagnosis (Blommaert et al, 2019;Krull et al, 2016;Reddick et al, 2009). It was a priori hypothesized that functional brain differences could be related to the behavioral outcomes (Billiet* et al, 2018;Kaiser et al, 2014;Reuter-Lorenz and Cimprich, 2013).…”