Self-reported sleep disturbances during chemotherapy mediate circulating IL-1β effects on subjective cognitive...

Chemotherapy can cause cognitive decline that may persist for years after treatment and reduce quality of life in cancer patients. Identifying factors during chemotherapy that contribute to post-treatment side effects could inform strategies to prevent or mitigate long-term consequences. Sleep disturbances, particularly difficulty falling or staying asleep, are highly prevalent during chemotherapy and can exacerbate cognitive symptoms. Although cross-sectional associations among cognitive decline, sleep disturbances, and inflammatory markers have been examined in cancer patients, the longitudinal dynamics of sleep and inflammation during treatment related to post-treatment cognition remain unclear. We hypothesized that increased sleep disturbances during chemotherapy predict worse cognitive decline after treatment, mediated by increased pro-inflammatory markers. To test this, 75 breast cancer patients provided blood samples to measure circulating inflammatory markers (IL-6, TNFα, IL-1β, CRP), completed questionnaires assessing sleep disturbance and perceived cognition, and underwent objective cognitive testing. Assessments occurred before, during, and approximately three months after chemotherapy. Longitudinal relationships among sleep disturbances, inflammation, and cognition were evaluated. Sleep disturbances increased during chemotherapy associated with concurrent increases in IL-6, TNFα, and IL-1β. Increased sleep disturbances during chemotherapy predicted decreased subjective, but not objective, cognition after treatment. Among inflammatory markers, increased IL-1β during chemotherapy predicted worse subjective cognition after treatment. Contrary to our hypothesis, sleep disturbances mediated the relationship between elevated IL-1β during chemotherapy and post-treatment subjective cognitive decline. These findings highlight sleep disturbance as a key, modifiable factor during chemotherapy that predicts persistent cognitive symptoms and suggest that improving sleep may mitigate cognitive deficits without directly modulating inflammation.