The overlap between epilepsy and Alzheimer’s disease and the consequences for treatment

ABSTRACT

Introduction: Alzheimer’s disease may be associated with both clinical and subclinical epileptic seizure activity. Once regarded as an epiphenomenon, epileptiform activity may, in fact, be an integral part of the Alzheimer’s phenotype, and may be not only a symptomatic therapeutic target but also a possible mechanism to retard or prevent disease progression.

Areas covered: The authors review clinical research articles with a focus on the semiology, epidemiology, and treatment of seizures in Alzheimer’s disease, and also look at some experimental animal model studies which have informed clinical thinking on seizure aetiopathogenesis. The evidence base for treatment decisions is sparse. A brief overview of the clinical assessment of Alzheimer’s disease patients considering relevant differential diagnoses and diagnostic pitfalls is presented.

Expert opinion: Studies of epileptic seizures in Alzheimer’s disease have become more frequent over the last 5–10 years. Understanding of seizure semiology, epidemiology, and possible pathogenesis has increased. However, the optimal management of seizures in this context remains unknown, largely due to the paucity of studies sufficient to examine this question. Clearly, such studies will be required, not only to inform clinicians about symptomatic control of seizures in Alzheimer’s disease but also to investigate whether this might impact on disease progression.

KEYWORDS:

• Alzheimer’s disease
• amyloid beta-peptides
• dementia
• epilepsy
• epileptiform activity
• seizures
• treatment

Article highlights

• Epileptic seizures may occur in the context of Alzheimer’s disease and Down syndrome.

• Seizures may be a consequence of shared pathogenetic mechanisms underlying cognitive decline in these patients, hence an integral part of disease phenotype rather than epiphenomena.

• Subclinical epileptiform activity may be more prevalent than overt seizures in AD and may contribute to the clinical decline.

• There are insufficient clinical trial data on which to base any definitive recommendations for the treatment of seizures in AD.

• The differential diagnosis of both seizure type and seizure etiology in AD is potentially broad.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded