Epilepsy in Alzheimer's Disease: Effect on Disease Progression

Epilepsy is a known comorbidity of Alzheimer's disease. In the past, it was considered to be a late complication of AD. Recent literature suggest seizures to be prevalent much earlier in the time course of the disease. Systematic reviews suggest the occurrence of at least one seizure in 10-22% of AD cases and of epilepsy in 5 out of 100 AD cases. One important factor leading to the underdiagnosis of epilepsy in AD, is the fact that it is difficult to diagnose epilepsy in patients with AD because of an overlap in symptomatology (e.g. speech arrest, staring, confusion, …) A recent pilot study showed that even subclinical epileptiform discharges, without overt epilepsy, were more frequent (42%) in patients with dementia due to AD than in healthy controls (10%). These subclinical epileptic discharges were diagnosed with prolonged electroencephalogram (EEG)-monitoring and magnetoencephalogram (MEG)-registration. There is overlap in AD and epilepsy pathogenesis. In both diseases, activation of microglia, astrogliosis, neuroinflammation and hippocampal neuronal loss has been described. Studies in mice have shown that hippocampal hyperexcitability is an early electrophysiological impairment in AD, and, that this might be a consequence of soluble Amyloid bèta oligomers. Another study in mice, expressing human Amyloid Precursor Protein (APP), showed hippocampal synchronized large amplitude potentials to be present before onset of spontaneous seizures, memory impairments or Amyloid bèta plaques. Low levels of soluble forms of Amyloid bèta might have increased excitability. Increased neuronal activity per se increases both Amyloid bèta and Tau secretion. This means that recurrent epileptic activity in AD might establish a vicious cycle. Since hippocampal hyperactivity might be an early electrophysiological impairment in AD according to rodent studies, even before memory impairment exist, the investigators thought it to be useful to track subclinical, hippocampal epileptic activity by use of magnetoencephalogram - high density electroencephalogram (MEG-EEG) in patients with MCI due to AD (aka a stage of predementia) and compare this prevalence to healthy controls. The investigators would also like to track evolution to AD in patients with MCI and subclinical epileptiform activity versus those without. This could support further investigations, with monitoring of the effect of several antiepileptic drugs in patients with MCI due to AD.