Working Memory Impairment Induced by Chemotherapy-A Narrative Review

Chemotherapy-associated cognitive impairment (CACI) is a common long-term complication of cancer treatment that predominantly affects attention, executive function, information processing, and working memory. Although considerable progress has been made in understanding its molecular basis, the relationship between chemotherapy-induced neurobiological alterations and the functional organization of working memory remains incompletely understood. This narrative review aims to integrate current evidence on the neuroanatomical organization of working memory, the molecular mechanisms underlying CACI, and neuroimaging findings in patients receiving chemotherapy. The review summarizes current knowledge regarding mitochondrial dysfunction, oxidative stress, neuroinflammation, blood-brain barrier disruption, purinergic signaling, and chemotherapy-specific mechanisms of central nervous system injury. Furthermore, the principal mechanisms by which commonly used chemotherapeutic agents reach or indirectly affect the brain are discussed. Clinical neuroimaging findings from selected malignancies are interpreted within the framework of the four-component model of working memory, including the visuospatial sketchpad, phonological loop, central executive, and episodic buffer. Current evidence indicates that chemotherapy induces structural and functional alterations involving the prefrontal cortex, parietal cortex, hippocampus, insula, anterior cingulate cortex, angular gyrus, and associated neural networks. These changes are accompanied by disturbances in executive control, visuospatial processing, verbal working memory, and multimodal information integration. However, considerable heterogeneity among available studies and the difficulty in distinguishing cancer-related from chemotherapy-induced cognitive impairment remain major limitations. By integrating molecular, neuroanatomical, and neuroimaging evidence, this review proposes a conceptual framework linking chemotherapy-induced brain alterations with dysfunction of specific working memory components. Future longitudinal studies combining multimodal neuroimaging, molecular biomarkers, and standardized neuropsychological assessment are needed to identify chemotherapy-specific patterns of cognitive dysfunction and support the development of personalized preventive and therapeutic strategies for cancer survivors.