Cognitive Impairment in Drug-Resistant Epilepsy: A Multidomain Systematic Review

Background: Drug-resistant epilepsy (DRE) is frequently accompanied by cognitive impairment across multiple neuropsychological domains. Objectives: We aimed to synthesize contemporary evidence on cognitive impairment, neurobiological correlates, potentially modifiable clinical factors, and treatment-related cognitive outcomes in predominantly adult populations with DRE. Methods: PubMed/MEDLINE and Web of Science were searched for studies published between January 2017 and September 2026, supplemented by citation searching. Twenty-two studies comprising 2359 participants were included, of whom 1616 (68.5%) had confirmed DRE. Eligibility was independently verified by a second reviewer, and risk of bias was assessed independently by two reviewers using design-specific Joanna Briggs Institute tools. Owing to substantial clinical and methodological heterogeneity, a structured qualitative synthesis was performed. Results: Cognitive impairment involved memory, executive function, attention, language, and processing- or psychomotor-speed-related performance. Cognitive performance was associated with distributed neurobiological abnormalities and with clinical factors including sleep quality, antiseizure medication exposure, and seizure burden. Treatment- and surgery-related cognitive outcomes varied across studies. The predominantly observational evidence and substantial heterogeneity limited causal inference. Conclusions: Cognitive impairment in DRE is heterogeneous and extends beyond memory dysfunction. Current evidence supports multidomain neuropsychological assessment and is compatible with a distributed network framework, although causal mechanisms remain uncertain.