How Much Difference Does Depression Make to the Outcome of Neuropsychological Assessments of Patients With Epilepsy?

ABSTRACT Background Cognitive impairment and depression are common comorbidities in people with epilepsy (PWE). This study investigated the extent to which the severity of depression affects specific cognitive domains and quality of life (QOL) in PWE. Methods In 732 PWE (age 18–82 years), Beck Depression Inventory (BDI) scores were correlated with performance in several cognitive domains (attention/executive functions, motor function, memory, language, visuo‐construction) and with QOL (using QOLIE‐10), individually and as superordinate compounds reflecting the range and intensity of general impairment. Results Forty‐five percent of patients had mild‐to‐severe depression. Cognitive domains were impaired in 43%–62% of patients. Depression correlated strongly with poorer QOL ( r = 0.65). In contrast, its correlations with cognition were significantly weaker ( r = 0.07–0.17), explaining less than 3% of the variance across all domains. The strongest correlation was with attention/executive functions. The overall impact of depression on the range and severity of cognitive impairments was mediated by its effect on these executive functions. The minimum BDI score difference required for a clinically significant cognitive difference (> 1 SD) was domain‐specific, ranging from 6 points for attention to 13 points for language. A 16‐point difference was needed for a significant change in QOL. Conclusion In PWE, depression has a severe primary impact on quality of life. Its direct effect on cognition, however, is minor. When a cognitive effect is present, it suggests hypofrontality impacting attention, executive functions, and motor skills, predominantly in the most severely depressed patients (BDI > 29). The influence of depression on global cognitive impairment is mediated through this executive dysfunction.