Antiseizure therapy attenuates cognitive decline in Alzheimer’s disease: A retrospective cohort study

Background Epileptic seizures and subclinical epileptiform activity are increasingly recognized as comorbidities in Alzheimer's disease (AD) and have been associated with accelerated cognitive decline. Whether antiseizure medication (ASM) therapy favorably influences cognitive trajectories in AD remains unclear. Objective To assess the effects of ASM therapy on cognitive trajectories in patients with AD with comorbid epilepsy, and to identify patient subgroups most likely to benefit. Methods We retrospectively studied 538 patients (403 AD only; 135 AD with comorbid epilepsy) treated with newer-generation ASMs between 2020 and 2025. Cognitive change over 24 months was assessed using the Mini-Mental State Examination (MMSE). Analyses included linear mixed-effects modeling, sliding window interaction analysis across baseline MMSE scores (11–29), and 1:1 propensity score matching stratified by baseline MMSE (≤21, 22–26, and ≥27). Results After propensity score matching, baseline MMSE scores were well balanced between the groups. The sliding window analysis suggested a subgroup-specific interaction between group and time in the MMSE (range 22–26), peaking at MMSE 25. In the 22–26 stratum, MMSE at 12 months was higher in the AD with comorbid epilepsy group than in the AD-only group (23.23 ± 0.46 versus 20.33 ± 0.52, p < 0.001). The 24-month difference (22.92 ± 1.37 versus 19.36 ± 0.99, p = 0.047) was borderline and considered exploratory. Conclusions Antiseizure therapy was associated with favorable cognitive trajectories in patients with AD and comorbid epilepsy, particularly with baseline MMSE 22–26. These exploratory findings suggest a potential therapeutic window that warrants confirmation in prospective studies.