Pathogenesis of comorbid epilepsy in Alzheimer's disease and use of perampanel, an AMPA receptor inhibitor.

INTRODUCTION: Alzheimer's disease (AD) and epilepsy frequently co-occur and are risk factors for each other's onset. In patients with AD-comorbid epilepsy, seizure control with appropriate anti-seizure medications (ASMs) is crucial, yet no established treatment guidelines exist. Recent studies indicate that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are involved in the pathogenesis of both diseases. Perampanel, an AMPAR antagonist, has been approved as an ASM.

AREAS COVERED: This review explains the relationship between AD and epilepsy and discusses the involvement of AMPARs. Furthermore, it focuses on and presents opinions regarding the role of AMPAR inhibitors in the treatment of AD-comorbid epilepsy. The authors searched for clinical studies that were published and identifiable in PubMed and Scopus (Jan 2015-Dec 2024) including the terms 'Alzheimer's disease' or 'dementia' with 'epilepsy' or 'seizure'.

EXPERT OPINION: Considering the hypothesis that AD and epilepsy are linked, creating a cycle that progresses both diseases via AMPARs, AMPAR inhibition may have beneficial effects in treatment of epilepsy in AD. Although evidence is limited, studies of perampanel have demonstrated symptomatic improvement in patients with AD-comorbid epilepsy. Perampanel may be particularly useful for specific subgroups of patients with AD-comorbid epilepsy, such as those with myoclonus, sleep disturbances, or poor medication adherence.