title: Incidence and impact of subclinical epileptiform activity in Alzheimer's disease.
abstract: Seizures are more frequent in patients with Alzheimer's disease (AD) and can hasten cognitive decline. However, the incidence of subclinical epileptiform activity in AD and its consequences are unknown. Motivated by results from animal studies, we hypothesized higher than expected rates of subclinical epileptiform activity in AD with deleterious effects on cognition.
  
  
  
  We prospectively enrolled 33 patients (mean age, 62 years) who met criteria for AD, but had no history of seizures, and 19 age-matched, cognitively normal controls. Subclinical epileptiform activity was assessed, blinded to diagnosis, by overnight long-term video-electroencephalography (EEG) and a 1-hour resting magnetoencephalography exam with simultaneous EEG. Patients also had comprehensive clinical and cognitive evaluations, assessed longitudinally over an average period of 3.3 years.
  
  
  
  Subclinical epileptiform activity was detected in 42.4% of AD patients and 10.5% of controls (p = 0.02). At the time of monitoring, AD patients with epileptiform activity did not differ clinically from those without such activity. However, patients with subclinical epileptiform activity showed faster declines in global cognition, determined by the Mini-Mental State Examination (3.9 points/year in patients with epileptiform activity vs 1.6 points/year in patients without; p = 0.006), and in executive function (p = 0.01).
  
  
  
  Extended monitoring detects subclinical epileptiform activity in a substantial proportion of patients with AD. Patients with this indicator of network hyperexcitability are at risk for accelerated cognitive decline and might benefit from antiepileptic therapies. These data call for more sensitive and comprehensive neurophysiological assessments in AD patient evaluations and impending clinical trials. Ann Neurol 2016;80:858-870.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.|Gladstone Institute of Neurological Disease, San Francisco, CA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Kamalini G
authors.initials: KG
authors.lastname: Ranasinghe
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Beagle
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Mizuiri
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Honma
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Dowling
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Darwish
authors.affiliation: Department of Neurology and Semel Institute for Neuroscience and Human Behavior in the Department of Psychiatry, University of California Los Angeles, Los Angeles, CA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Van Berlo
authors.affiliation: Departments of Psychiatry and Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.|Veterans Affairs Medical Center, San Francisco, CA.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Barnes
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.|Epilepsy Center, Department of Neurology, University of California San Francisco, San Francisco, CA.
authors.forename: Mary
authors.initials: M
authors.lastname: Mantle
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Karydas
authors.affiliation: Department of Neurology and Semel Institute for Neuroscience and Human Behavior in the Department of Psychiatry, University of California Los Angeles, Los Angeles, CA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology and Neurobiology, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Erik D
authors.initials: ED
authors.lastname: Roberson
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Epilepsy Center, Department of Neurology, University of California San Francisco, San Francisco, CA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Garcia
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.|Epilepsy Center, Department of Neurology, University of California San Francisco, San Francisco, CA.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Kirsch
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA.|Gladstone Institute of Neurological Disease, San Francisco, CA.
authors.forename: Lennart
authors.initials: L
authors.lastname: Mucke
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
authors.forename: Srikantan S
authors.initials: SS
authors.lastname: Nagarajan
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology*; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D015897:Comorbidity; D004569:Electroencephalography; D005260:Female; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D062706:Prodromal Symptoms; D011446:Prospective Studies; D012640:Seizures / Q000453:epidemiology*