Amyloid-β: a potential link between epilepsy and cognitive decline

Michele Romoli, Arjune Sen, Lucilla Parnetti, Paolo Calabresi, Cinzia Costa

Research output: Contribution to journalReview articlepeer-review


People with epilepsy — in particular, late-onset epilepsy of unknown aetiology — have an elevated risk of dementia, and seizures have been detected in the early stages of Alzheimer disease (AD), supporting the concept of an epileptic AD prodrome. However, the relationship between epilepsy and cognitive decline remains controversial, with substantial uncertainties about whether epilepsy drives cognitive decline or vice versa, and whether shared pathways underlie both conditions. Here, we review evidence that amyloid-β (Aβ) forms part of a shared pathway between epilepsy and cognitive decline, particularly in the context of AD. People with epilepsy show an increased burden of Aβ pathology in the brain, and Aβ-mediated epileptogenic alterations have been demonstrated in experimental studies, with evidence suggesting that Aβ pathology might already be pro-epileptogenic at the soluble stage, long before plaque deposition. We discuss the hypothesis that Aβ mediates — or is at least a major determinant of — a continuum spanning epilepsy and cognitive decline. Serial cognitive testing and assessment of Aβ levels might be worthwhile to stratify the risk of developing dementia in people with late-onset epilepsy. If seizures are a clinical harbinger of dementia, people with late-onset epilepsy could be an ideal group in which to implement preventive or therapeutic strategies to slow cognitive decline.

Original languageEnglish
Pages (from-to)469-485
Number of pages17
JournalNature Reviews Neurology
Issue number8
Publication statusPublished - Aug 2021

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Amyloid-β: a potential link between epilepsy and cognitive decline'. Together they form a unique fingerprint.

Cite this