Cognitive function at the time of focal epilepsy diagnosis is not associated with treatment resistance

Seizures can impact cognition both acutely and chronically. However, among those without significant comorbidities and broadly average cognition at epilepsy onset, the relationship between cognitive function at the time of diagnosis and long-term seizure control has been relatively unexplored. This analysis investigated associations between participant characteristics including specific aspects of cognitive performance at the time of focal epilepsy diagnosis and antiseizure medication (ASM) treatment resistance.

This was a secondary analysis of Human Epilepsy Project (HEP) data, which enrolled people with newly diagnosed focal epilepsy and broadly average cognition (estimated IQ ≥ 70) from June 29, 2012, to September 1, 2019. Participants analyzed in this study were between 18 and 60 years old, and scored within an acceptable range (i.e., Standard Score of ≥80) on measures estimating premorbid cognitive ability were offered the Cogstate Brief Battery (CBB). Participant characteristics were analyzed, including the presence of any anxiety disorders or depression, and summary CBB scores. HEP participants who were classified by the study as treatment resistant if they had experienced failure to achieve seizure freedom after two adequate trials of ASMs. Treatment resistance was modeled using multiple logistic regression to assess for independent associations between attention and working memory after correcting for the presence of the other potentially explanatory variables.

200 HEP participants had comprehensive enrollment records including CBB results and complete seizure outcome data for analysis in this study. After correcting for potentially confounding variables, there were no independent associations between cognitive measures on the CBB at the time of enrollment and subsequent development of ASM treatment resistance. Specifically, z-scores for reaction time on the CBB (an average of the CBB Identification and Detection tests) were not associated with treatment resistance (p = 0.51) and z-scores for memory performance (an average of the CBB One Card Learning test and One Back tests) were not associated with treatment resistance (p = 0.24). There were no significant independent associations between age or the presence of depression or anxiety disorders at the time of CBB testing and treatment resistance. However, there was an independent association between employment status and treatment resistance, with those who were employed or students (>18 years old) at the time of enrollment and CBB testing having 0.35 times lower odds of treatment resistance (95 %CI 0.15-0.81, p = 0.01).

The findings from this study suggest that in otherwise healthy people with new onset focal epilepsy who have broadly average intelligence, attention and working memory as measured by the CBB at the time of diagnosis is not associated with treatment resistance. Although performance on cognitive testing at epilepsy onset may not be predictive of risk of treatment resistance in this population, other individual characteristics such as employment status at the time of diagnosis may be indirect markers of long-term seizure outcomes and require further investigation.