Affiliations: [a] Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA
| [b]
University of California, San Francisco Comprehensive Epilepsy Center, San Francisco, CA, USA
Correspondence:
[*]
Correspondence to: Niyatee Samudra, MD, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94158, USA. Tel.: +1 415 353 2057; E-mail: niyatee.samudra@ucsf.edu.
Abstract: Cortical network hyperexcitability related to synaptic dysfunction in Alzheimer’s disease (AD) is a potential target for therapeutic intervention. In recent years, there has been increased interest in the prevalence of silent seizures and interictal epileptiform discharges (IEDs, or seizure tendency), with both entities collectively termed “subclinical epileptiform activity” (SEA), on neurophysiologic studies in AD patients. SEA has been demonstrated to be common in AD, with prevalence estimates ranging between 22-54%. Converging lines of basic and clinical evidence imply that modifying a hyperexcitable state results in an improvement in cognition. In particular, though these results require further confirmation, post-hoc findings from a recent phase II clinical trial suggest a therapeutic effect with levetiracetam administration in patients with AD and IEDs. Here, we review key unanswered questions as well as potential clinical trial avenues. Specifically, we discuss postulated mechanisms and treatment of hyperexcitability in patients with AD, which are of interest in designing future disease-modifying therapies. Criteria to prompt screening and optimal screening methodology for hyperexcitability have yet to be defined, as does timing and personalization of therapeutic intervention.
