Seizures and epileptiform activity in early Alzheimer disease: how hard should we be looking?

Commentary My standard epilepsy talk for medical students used to include the following: The incidence of epilepsy has a bimodal distribution , and the causes of epilepsy in children are different from those in older adults. New-onset epilepsy in the elderly is often a consequence of accumulated injuries to the brain, including from stroke, brain tumors, and neurodegenerative diseases. Although I did not explicitly say that epilepsy was an end-stage feature of Alzheimer disease (AD)—the result of advanced neuronal and synaptic loss—I implied that this was the case and made that implicit assumption myself. Clearly, this thinking needed revision. There is now substantial and growing literature addressing the interface between Alzheimer disease and epilepsy. Epidemiological studies clearly indicate that Alzheimer disease confers an increased risk of seizures and epilepsy: The incidence rate is increased about sevenfold in patients with AD compared to non-demented controls (1). A number of potential risk factors for developing seizures in AD have been identified , including antipsychotic drug use, African-American race, epileptiform findings on EEG, and greater cognitive impairment at baseline (2, 3). However, the most robust association has been with young age at dementia onset (4). While seizures can appear at any stage of the disease, the odds of developing epilepsy in AD are highest in young patients with AD and early in the disease course. Those with genetic causes of AD, who also have earlier onset of disease, appear to be at especially high risk of developing comorbid epilepsy. Patients with the most common IMPORTANCE: 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 amnes-tic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity. DESIGN PATIENTS: 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). MAIN OUTCOMES AND MEASURES: Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications. RESULTS: Patients with aMCI who …