Inhibiting Epileptiform Activity in Cognitive Disorders: Possibilities for a Novel Therapeutic Approach

Abstract

Cognitive impairment is a common and seriously debilitating symptom of various mental and neurological disorders including autism, attention deficit hyperactivity disorder, multiple sclerosis, epilepsy, and neurodegenerative diseases, like Alzheimer's disease. In these conditions, high prevalence of epileptiform activity emerges as a common pathophysiological hallmark. Growing body of evidence suggests that this discrete but abnormal activity might have a long-term negative impact on cognitive performance due to neuronal circuitries' remodeling, altered sleep structure, pathological hippocampo-cortical coupling, and even progressive neuronal loss. In animal models, epileptiform activity was shown to enhance the formation of pathological amyloid and tau proteins that in turn trigger network hyperexcitability. Abolishing epileptiform discharges might slow down the cognitive deterioration. These findings might provide basis for therapeutic use of antiepileptic drugs in neurodegenerative cognitive disorders. The aim of our review is to describe the data on the prevalence of epileptiform activity in various cognitive disorders, to summarize the current knowledge of the mechanisms of epileptic activity in relation to cognitive impairment, and to explore the utility of antiepileptic drugs in the therapy of cognitive disorders. We also propose future directions for drug development and novel therapeutic interventions targeting epileptiform discharges in these disorders.

Keywords: antiepileptic drugs; cognitive decline; electroencephalography; epileptiform activity; memory consolidation; neurocognitive disorder.