Abstracts

Rationale: Cognitive impairment is one of the most common complaints for persons with epilepsy. These impairments are not only associated with seizures, but are also regularly reported as side effects of antiepileptic drugs (AEDs). Previous studies have examined cognitive effects of both AED monotherapy and polytherapy, yet there is limited research on these differences with respect to both subjective and objective cognition. The current study uses data from previous research conducted by the CDC-sponsored Managing Epilepsy Well (MEW) Network collaborative. Study data from sites within the Network has been collated into a repository known as the MEW Database, managed at Case Western Reserve University. We used three distinct archival datasets from: (1) the HOBSCOTCH efficacy trial at Dartmouth-Hitchcock Medical Center (HOB-1), (2) the multi-site replication trial (HOB-2), and (3) epilepsy self-management research conducted at the NYU School of Medicine. Methods: This cross-sectional analysis of baseline data from three datasets were combined to determine how number of AEDs and AED type are associated with subjective (patient reported) and objective (examiner assessed) cognition. Subjective cognition was captured using the cognitive subscale of the QOLIE-31 in all three datasets (n=224), while objective cognition was measured using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) in the HOB-1 dataset (n=65) and the Brief Test of Adult Cognition by Telephone (BTACT) in the HOB-2 dataset (n=91). Multivariable linear regression was utilized for our initial assessments, followed by propensity score matching to provide stronger control of covariates. Matching was based on significantly different covariates, such as education, depression and history of prior epilepsy surgery; this resulted in 51 subjects from the HOB-1 dataset and 73 subjects from the HOB-2 dataset. Nonparametric statistical tests were utilized to compare these matched subjects. Results: Subjective cognitive impairment was significantly worse among individuals on three or more AEDs vs. one AED (adjusted p = 0.03), while the other pairwise comparisons of AED number demonstrated no significant differences (adjusted p > 0.05). These findings were consistent with our propensity score matched comparison of monotherapy (1 AED) and polytherapy (2+ AEDs), which indicated that polytherapy was associated with a worse overall subjective cognition (adjusted p = 0.02), and impairment in specific subdomains of the RBANS (Visuospatial p = 0.03) and BTACT (Episodic Verbal Memory p < 0.01, Working Memory p < 0.01, Processing Speed p < 0.01). There were no significant differences in subjective vs. objective cognition based on the type (older vs. newer generation AED) and the pharmacodynamics of the AED (adjusted p > 0.05). Conclusions: Being prescribed a greater number of AEDs is significantly and negatively associated with subjective and objective cognition in persons with epilepsy and is in line with previous research. AED type did not, in itself, appear to be associated with subjective cognition. Our findings suggest that ineffective AEDs should be replaced, rather than introducing additional AEDs to a treatment regimen. Further, while subjective and objective cognition assessments were both sensitive at detecting differences based on AED status, the neuropsychological objective subdomains offer additional and specific insights into how cognition is impaired with AEDs. Funding: Eisai Inc. FYC-IIS-M001-1014