Chemotherapy-Related Cognitive Impairment and Changes in Neural Network Dynamics

BACKGROUND AND OBJECTIVES: This systematic review aims to synthesize the current literature on the association between chemotherapy (CTX) and chemotherapy-related cognitive impairment (CRCI) with functional and structural brain alterations in patients with noncentral nervous system cancers. METHODS: A comprehensive search of the PubMed/MEDLINE, Web of Science, and Embase databases was conducted, and results were reported following preferred reporting items for systematic review and meta-analyses guidelines. Data on study design, comparison cohort characteristics, patient demographics, cancer type, CTX agents, neuroimaging methods, structural and functional connectivity (FC) changes, and cognitive/psychological assessments in adult patients were extracted and reported. Study quality was assessed using an adapted version of the Newcastle-Ottawa Scale (NOS) for observational studies. Qualitative synthesis of cognitive and psychological testing outcomes, functional and structural connectivity changes, and their associations with CRCI were performed. RESULTS: From 11,335 records identified, 63 studies analyzing 3,642 patients were included. Study designs included 24 prospective studies, 1 retrospective study, 36 cross-sectional studies, and 2 longitudinal studies. Most studies (75%) focused on patients with breast cancer. Common neuroimaging techniques included functional magnetic resonance imaging and diffusion tensor imaging. Postchemotherapy, many studies reported structural and FC alterations in brain networks such as the default mode, central executive, and dorsal attention networks. Cognitive function was assessed in 56 of the 63 included studies. Of the studies examining specific cognitive domains, 64% reported worsened learning and memory, 56% found impaired processing speed, and 70% identified deficits in attention/working memory in patients after CTX. Of the studies examining associations between connectivity changes and worsened cognitive function, 72% reported significant correlations in postchemotherapy patients. However, most of these studies were of low evidence, while 45% of high evidence-level studies, including prospective cohort studies, did not find significant associations between connectivity alterations and cognitive impairments. DISCUSSION: While there is evidence suggesting CTX affects brain connectivity and neural network dynamics that can lead to cognitive difficulties, the findings are inconsistent. More robust and standardized research is needed to conclusively determine the extent of these effects and to develop targeted interventions for mitigating potential cognitive impairments in patients undergoing systemic treatment.