Epilepsy and EEG abnormalities in neurodegenerative dementias: toward a system epilepsy framework

Epilepsy and epileptiform activity represent underrecognized yet clinically significant features of neurodegenerative dementias, with emerging evidence suggesting they may contribute to disease progression rather than merely representing epiphenomena of neuronal loss. This comprehensive review examines the epidemiology, clinical presentation, electroencephalographic findings, and pathophysiological mechanisms underlying seizure activity in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Meta-analytic data demonstrate elevated seizure prevalence across all three conditions, with cumulative probabilities of 13.4% for AD, 14.7% for DLB, and 3.0% for FTD, representing risk elevations of approximately 6- to 10-fold compared to age-matched controls. Critically, subclinical epileptiform activity detected through prolonged electroencephalographic monitoring affects up to 42-54% of AD patients and is associated with 1.5-fold accelerated cognitive decline. Each dementia subtype exhibits characteristic electroencephalographic signatures: AD demonstrates progressive spectral slowing with predominantly left temporal epileptiform discharges; DLB shows highly characteristic slowing of the dominant rhythm below 8 Hz with high diagnostic accuracy; and FTD displays relatively preserved background activity with frontal-temporal hypoconnectivity. We synthesize evidence from transcranial magnetic stimulation studies demonstrating distinct patterns of cortical excitability alterations across these conditions, with AD showing bilateral increases in cortical excitability and reduced GABAergic and cholinergic inhibition. Building upon these observations, dementia-associated epilepsy may be conceptualized within the framework of system epilepsies, arising from dysfunction of vulnerable neural networks rather than discrete lesions. This paradigm shift has profound therapeutic implications, supporting network-targeted interventions and the potential disease-modifying role of antiseizure medications. We conclude by presenting clinical recommendations for monitoring and treatment, emphasizing the need for prolonged electroencephalographic evaluation and consideration of empirical treatment for subclinical epileptiform activity associated with cognitive fluctuations.