Abstracts

Rationale: The role of epileptiform activity and hyperexcitability in Alzheimer’s disease has gained significant interest recently. The first study utilizing prolonged (24 hour) EEG recordings as well as MEG recordings in subjects with Alzheimer’s disease reported subclinical epileptiform activity in 42% of people with Alzheimer’s disease without a prior history of epilepsy (Vossel et al, 2016).  Subclinical epileptiform activity in these subjects was associated with faster rates of cognitive decline, suggesting that epileptiform activity may accelerate the course of Alzheimer’s disease.  However, subjects in that study were quite young (mean age ~ 62 years old, with mean age of onset of cognitive symptoms of ~57 years old) and were more typical of patients with early-onset Alzheimer’s disease.  Here we sought to determine how common subclinical epileptiform activity is in patients with late-onset Alzheimer’s disease (symptom onset after age 65 years), which comprises over 90% of all AD cases. Methods: We recruited cognitively normal subjects and subjects with amnestic mild cognitive impairment (aMCI) or mild dementia due to Alzheimer’s disease to undergo 3-day ambulatory scalp EEGs.  Subjects were recruited from the Massachusetts General Hospital Memory Disorders Unit, as well as from two ongoing, longitudinal observational cohort studies:  the Massachusetts Alzheimer’s Disease Research Center’s Longitudinal Cohort study, and the Boston University Alzheimer’s Disease Center’s HOPE study.  All subjects were between the ages of 66-88 years old, and had no prior history of epilepsy or other risk factors for epilepsy. Scalp EEG electrodes were placed according to the international 10-20 system with additional T1 and T2 anterior temporal electrodes.  Scalp EEGs were visually analyzed by a board-certified clinical neurophysiologist for epileptiform discharges and other abnormalities, blinded to the cognitive status of each subject. Results: We recruited 7 subjects with aMCI (mean age = 74), 4 subjects with mild AD dementia (mean age = 74), and 8 healthy control subjects (mean age = 71).   We found visible epileptiform discharges in 5 of 11 subjects with aMCI and mild AD dementia (45%) and in none of the 8 healthy control subjects.  The majority of epileptiform discharges occurred during sleep.  The distribution of epileptiform discharges was left temporal in 2 subjects, right temporal in 1 subject, and multifocal (left temporal, right temporal, and bifrontal) in 2 subjects.  Focal slowing (most commonly left temporal slowing) was seen in 4 patients, and diffuse slowing (left and right temporal slowing) was seen in 3 patients with aMCI or mild AD dementia.   Conclusions: Subclinical epileptiform discharges are common in patients in prodromal stages of late-onset Alzheimer’s disease.  Prolonged recordings capturing the asleep state were key to detecting these abnormalities.  Most epileptiform discharges are temporal in location.  More work is needed to better understand the natural history of these abnormalities in Alzheimer’s disease and their effect on disease trajectory.   Funding: NIH NINDS R25 NS06574308 and K24 NS08856803; MGH Fund for Medical Discovery