Epilepsy and Alzheimer's Disease: Current Concepts and Treatment Perspective on Two Closely Related Pathologies

Abstract

The literature on epileptic seizures in Alzheimer's disease has significantly increased over the past decades. Remarkably, several studies suggest a bi-directional link between these two common neurological diseases, with either condition carrying a nearly 2-fold risk of contracting the other in comparison to healthy subjects. In this respect, evidence from both clinical and preclinical studies indicates that epileptogenesis and neurodegeneration possibly share common underlying mechanisms. However, the precise association between epileptogenesis and neurodegeneration still needs to be fully elucidated. Targeted intervention to reduce abnormal network hyperexcitability might constitute a therapeutic strategy to postpone the onset of later neurodegenerative changes and consequent cognitive decline by many years in patients. By virtue of this, an early diagnosis and treatment of seizures in patients with Alzheimer's disease should be pursued. To date, no guidelines are available for treating epileptic activity in this context, largely due to the paucity of studies sufficient to answer the related questions. Accordingly, clinical trials are mandatory, not only to inform clinicians about symptomatic management of seizures in Alzheimer's disease patients but also to detect if treatment with antiseizure medications could have disease-modifying effects. Moreover, it will be fundamental to expand the application of animal models of Alzheimer's disease to comorbid conditions, such as epilepsy both to reveal the mechanisms underlying seizure onset and to better define their role in cognitive decline. Such models could also be useful to identify pharmacological compounds having therapeutically effectiveness as well as reliable early biomarkers for seizures in Alzheimer's disease.

Keywords: Alzheimer’s disease; Epilepsy; network hyperexcitability; neurological comorbidities; perspective of treatment; pharmacology.