Epileptic activity in Alzheimer's disease: causes and clinical relevance

Abstract

Epileptic activity is frequently associated with Alzheimer's disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer's disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer's disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer's disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer's disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer's disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer's disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline.

Figure. Hypothetical model of the correlation between amyloid β and tau deposition and network alterations in Alzheimer’s disease

Proposed temporal associations between total brain amyloid β (plaques) and tau (neurofibrillary tangles) deposition, hippocampal hyperactivation, and epileptic activity. Although hippocampal hyperactivation is restricted to the stage of mild cognitive impairment, epileptiform activity and seizures can occur throughout the course of mild cognitive impairment and Alzheimer’s disease..^,,,,