Association of epileptiform abnormalities and seizures in Alzheimer disease.

Lam, Alice D; Sarkis, Rani A; Pellerin, Kyle R; Jing, Jin; Dworetzky, Barbara A; Hoch, Daniel B; Jacobs, Claire S; Lee, Jong Woo; Weisholtz, Daniel S; Zepeda, Rodrigo; Westover, M Brandon; Cole, Andrew J; Cash, Sydney S

OBJECTIVE Examine the relationship between scalp EEG biomarkers of hyperexcitability in Alzheimer's disease (AD) and determine how these electrical biomarkers relate to the clinical expression of seizures in AD. METHODS In this cross-sectional study, we performed 24-hour ambulatory scalp EEGs on 43 cognitively normal elderly healthy controls (HC), 41 early-stage AD participants with no history or risk factors for epilepsy (AD-NoEp), and 15 early-stage AD participants with late-onset epilepsy related to AD (AD-Ep). Two epileptologists, blinded to diagnosis, visually reviewed all EEGs and annotated all potential epileptiform abnormalities. A panel of 9 epileptologists, blinded to diagnosis, was then surveyed to generate a consensus interpretation of epileptiform abnormalities in each EEG. RESULTS Epileptiform abnormalities were seen in 53% of AD-Ep, 22% of AD-NoEp, and 4.7% of HC participants. Specific features of epileptiform discharges, including high frequency, robust morphology, right temporal location, and occurrence during wakefulness and REM, were associated with clinical seizures in AD. Multiple electrical biomarkers concordantly demonstrated a pattern of left temporal lobe hyperexcitability in early stages of AD, whereas clinical seizures in AD were often associated with bi-temporal hyperexcitability. Frequent small sharp spikes were specifically associated with epileptiform EEGs and thus identified as a potential biomarker of hyperexcitability in AD. CONCLUSION Epileptiform abnormalities are common in AD, but not all equivalent. Specific features of epileptiform discharges are associated with clinical seizures in AD. Given the difficulty recognizing clinical seizures in AD, these EEG features could provide guidance on which AD patients are at high risk for clinical seizures.