The impact of long-term antiseizure treatment on cognitive decline in late-onset epileptic prodromal Alzheimer’s disease: an exploratory study

Background The well-documented bidirectional relationship between Alzheimer’s disease (AD) and epilepsy suggests that seizures are not merely a complication of AD but may also contribute to disease progression. Emerging evidence indicates that antiseizure medications (ASMs) could potentially slow the disease course and act as disease-modifying agents if initiated early. Objectives We investigated the long-term cognitive and functional effects of ASMs when introduced at the prodromal stage of AD. Methods Twenty-two sporadic epileptic prodromal AD patients (epADs) and 21 matched subjects without epilepsy (nepADs) were followed for a median of 7 years. Baseline cognition, daily functioning, clinical/paraclinical features, and pharmacological profiles were compared. Annual assessments included cognition, pharmacological burden, and functional impairment. Results At the final follow-up, epADs evidenced more preserved cognition than nepADs, reflecting a significantly slower annual rate of cognitive decline (−1.2 ± 0.9 vs. −2.7 ± 2.4 points/year on the MMSE score, respectively; p = 0.01). They were also less likely to require neuroleptics (9.1% vs. 47.6%, p < 0.01) or memantine (0% vs. 28.6%, p < 0.01). However, epADs and nepADs had the same proportion of Alzheimer’s dementia at the final follow-up visit (90.9% vs. 90.5%, p = 0.96). Despite being significant, these results had low statistical power due to our small sample size and should be considered exploratory. Conclusion Our findings support the idea that early ASM treatment may attenuate cognitive decline in sporadic prodromal AD patients with comorbid epilepsy. However, these benefits were not accompanied by a lower dementia rate at the final follow-up visit, suggesting that ASMs alone are insufficient for sustained disease modification. Combinatorial therapeutic strategies may be needed to achieve long-term neuroprotection in AD.