Alzheimer disease: seizures and epileptiform activity in the early stages

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.

A retrospective observational study from 2007 to 2012 has described common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment ( aMCI ) or early Alzheimer disease who also have epilepsy or subclinical epileptiform activity.

Researchers at Memory and Aging Center, University of California, San Francisco ( UCSF ) have studied 54 patients with a diagnosis of aMCI plus epilepsy ( n = 12 ), Alzheimer disease plus epilepsy ( n = 35 ), and Alzheimer disease plus subclinical epileptiform activity ( n = 7 ).

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 = 0.02 ).

Patients with Alzheimer’s disease who had epilepsy presented with cognitive decline 5.5 years earlier than patients with Alzheimer’s disease who did not have epilepsy ( 64.8 vs 70.3 years; P =0.001 ).

Patients with Alzheimer’s disease 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 Alzheimer’s disease was nonuniform ( P less than 0.001 ), 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 ( Lamictal ) and Levetiracetam ( Keppra ) than for Phenytoin.

In conclusion, common clinical features of patients with aMCI- or AD-associated epilepsy 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. ( Xagena )

Vossel KA et al, JAMA Neurol 2013;70:1158-1166


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