Meta-analyses of executive function deficits in chemotherapy-treated rodent models

Abstract

People diagnosed with cancer who undergo chemotherapy commonly encounter cognitive changes, particularly in executive functions (EFs). EFs support goal-directed behaviours, with EF deficits implicated in various neurocognitive impairments. We conducted five meta-analyses of the rodent models to investigate the impact of chemotherapy across five EF domains. A systematic search across PubMed, Web of Science, Scopus, and PsycINFO yielded 56 eligible papers. Our findings supported the clinical literature suggesting the selective impact of chemotherapy on different EF domains. Specifically, chemotherapy-treated animals performed significantly more poorly than controls in tasks assessing working memory, behavioural flexibility, and problem-solving, with no significant group differences in inhibition or attention. Subgroup analyses revealed that alkylating agents, antitumor antibiotics, and combination therapies were strongly associated with working memory deficits, whereas mitotic inhibitors were not. Rodent species, strain, age, sex, number of treatments, and time of behavioural assessment since the end of treatment did not moderate the drug effect on any assessed EF domains. To increase the generalisability and translational validity of the results, the overall reporting quality of animal studies needs to be improved with more details on randomisation, blinding, sample sizes, and criteria for animal exclusions.