title: Seizures and epileptiform activity in the early stages of Alzheimer disease.
abstract: OBJECTIVE
  Epileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease.
  
  
  OBJECTIVE
  To describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity.
  
  
  METHODS
  Retrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco.
  
  
  METHODS
  We studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7).
  
  
  METHODS
  Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications.
  
  
  RESULTS
  Patients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P < .001), clustering near the onset of cognitive decline. Epilepsies were most often complex partial seizures (47%) and more than half were nonconvulsive (55%). Serial or extended EEG monitoring appeared to be more effective than routine EEG at detecting interictal and subclinical epileptiform activity. Epileptic foci were predominantly unilateral and temporal. Of the most commonly prescribed antiepileptics, treatment outcomes appeared to be better for lamotrigine and levetiracetam than for phenytoin.
  
  
  CONCLUSIONS
  Common clinical features of patients with aMCI- or AD-associated epilepsy at our center included early age at onset of cognitive decline, early incidence of seizures in the disease course, unilateral temporal epileptic foci detected by serial/extended EEG, transient cognitive dysfunction, and good seizure control and tolerability with lamotrigine and levetiracetam. Careful identification and treatment of epilepsy in such patients may improve their clinical course.
authors.affiliation: Gladstone Institute of Neurological Disease, San Francisco, California2Memory and Aging Center, Department of Neurology, University of California, San Francisco, California.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Beagle
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.forename: Huidy
authors.initials: H
authors.lastname: Shu
authors.forename: Suzee E
authors.initials: SE
authors.lastname: Lee
authors.forename: Georges
authors.initials: G
authors.lastname: Naasan
authors.forename: Manu
authors.initials: M
authors.lastname: Hegde
authors.forename: Susannah B
authors.initials: SB
authors.lastname: Cornes
authors.forename: Maya L
authors.initials: ML
authors.lastname: Henry
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Nelson
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.forename: Michael D
authors.initials: MD
authors.lastname: Geschwind
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.forename: Tina
authors.initials: T
authors.lastname: Shih
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Kirsch
authors.forename: Paul A
authors.initials: PA
authors.lastname: Garcia
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Lennart
authors.initials: L
authors.lastname: Mucke
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology*; D000927:Anticonvulsants / Q000627:therapeutic use; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D012189:Retrospective Studies; D012640:Seizures / Q000150:complications / Q000209:etiology / Q000503:physiopathology*
chemical_list: D000927:Anticonvulsants