Colaes Rob, Schroyen Gwen, Radwan Ahmed, Gavrila Laic Rebeca Alejandra, Helsper Shannon, Himmelreich Uwe, Hatse Sigrid, Smeets Ann, Caeyenberghs Karen, Sunaert Stefan, Deprez Sabine
Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Leuven Brain Institute, KU Leuven, Leuven, Belgium.
Cancer. 2025 Oct 1;131(19):e70095. doi: 10.1002/cncr.70095.
The pathophysiology of chemotherapy-induced cognitive impairment (CICI) remains unclear. Besides direct neurotoxicity, chemotherapy may trigger peripheral proinflammatory responses leading to neuroinflammation and neuronal injury. This longitudinal study investigated changes in peripheral inflammatory and neuronal markers, and multimodal magnetic resonance imaging measures from pre-to post-chemotherapy, and their potential role in CICI.
This study included 32 women receiving chemotherapy for early breast cancer (C+), 35 patients not exposed to chemotherapy (C-), and 46 healthy women (HC) age- and education-matched. Participants were assessed at diagnosis (T0), 3 months post-chemotherapy (T1), and 1 year post-chemotherapy (T2), or at matched intervals. Differences over time were assessed in cognitive outcomes, peripheral inflammatory and neuronal markers, and multimodal magnetic resonance imaging measures, reflecting white matter (WM) lesions, magnetic resonance spectroscopy metabolites, WM microstructure, and the diffusion tensor imaging along the perivascular space (DTI-ALPS) index. To investigate changes in WM structure, the authors performed a longitudinal fixel-based analysis on multi-shell diffusion-weighted images. Associations between peripheral inflammation and WM microstructure were explored, as well as their relationship to both subjective and objective cognitive outcomes.
This study observed alterations after chemotherapy in subjective and objective cognition, inflammatory profiles, neurofilament light chain, the DTI-ALPS index, and WM microstructure within the left inferior longitudinal fasciculus and in the genu of the prefrontal corpus callosum. Alterations in peripheral inflammatory profiles were associated with worse performance in objective cognition, but not with changes in WM microstructure.
Peripheral inflammatory responses and alterations in WM microstructure are potential key mechanisms underlying CICI.
化疗诱导的认知障碍（CICI）的病理生理学仍不清楚。除了直接神经毒性外，化疗可能引发外周促炎反应，导致神经炎症和神经元损伤。这项纵向研究调查了化疗前后外周炎症和神经元标志物的变化，以及多模态磁共振成像测量结果，及其在CICI中的潜在作用。
本研究纳入了32名接受早期乳腺癌化疗的女性（C+组）、35名未接受化疗的患者（C-组）以及46名年龄和教育程度匹配的健康女性（HC组）。参与者在诊断时（T0）、化疗后3个月（T1）和化疗后1年（T2）或在匹配的时间间隔进行评估。评估了认知结果、外周炎症和神经元标志物以及多模态磁共振成像测量结果随时间的差异，这些测量结果反映了白质（WM）病变、磁共振波谱代谢物、WM微观结构以及沿血管周围间隙的扩散张量成像（DTI-ALPS）指数。为了研究WM结构的变化，作者对多壳扩散加权图像进行了基于体素的纵向分析。探讨了外周炎症与WM微观结构之间的关联，以及它们与主观和客观认知结果的关系。
本研究观察到化疗后主观和客观认知、炎症特征、神经丝轻链、DTI-ALPS指数以及左下纵束和前额叶胼胝体膝部的WM微观结构发生了改变。外周炎症特征的改变与客观认知表现较差有关，但与WM微观结构的变化无关。
外周炎症反应和WM微观结构的改变是CICI潜在的关键机制。
