A growing body of evidence has demonstrated a link between Alzheimer disease (AD)
and epilepsy. Late-onset epilepsy and epileptiform activity can precede cognitive
deterioration in AD by years, and its presence has been shown to predict a faster
disease course. In animal models of AD, amyloid and tau pathology are linked to cortical
network hyperexcitability that precedes the first signs of memory decline. Thus, detection
of epileptiform activity in AD has substantial clinical importance as a potential
novel modifiable risk factor for dementia. In this Review, we summarize the epidemiological
evidence for the complex bidirectional relationship between AD and epilepsy, examine
the effect of epileptiform activity and seizures on cognition in people with AD, and
discuss the precision medicine treatment strategies based on the latest research in
human and animal models. Finally, we outline some of the unresolved questions of the
field that should be addressed by rigorous research, including whether particular
clinicopathological subtypes of AD have a stronger association with epilepsy, and
the sequence of events between epileptiform activity and amyloid and tau pathology.
