Artificial and natural interventions for chemotherapy- and / or radiotherapy-induced cognitive impairment A systematic review of animal studies

Background: Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural interventions (plant/endogenously-derived) to reduce treatment-related cognitive impairments. 

Methods: PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched and SYRCLE's tool was used for risk of bias assessment of the 134 included articles. 

Results: High variability was observed and risk of bias analysis showed overall poor quality of reporting. Results generally showed positive effects in the intervention group versus cancer-therapy only group (67% of 156 cognitive measures), with only 15 (7%) measures reporting cognitive impairment despite intervention. Both artificial (61%) and natural (75%) interventions prevented cognitive impairment. Artificial interventions involving GSK3B inhibitors, PLX5622, and NMDA receptor antagonists, and natural interventions utilizing melatonin, curcumin, and N-acetylcysteine, showed most consistent outcomes. 

Conclusions: Both artificial and natural interventions may prevent cognitive impairment in rodents, which merit consideration in future clinical trials. Greater consistency in design is needed to enhance the generalizability across studies, including timing of cognitive tests and description of treatments and interventions.