Sleep EEG Changes in Preclinical Alzheimer Disease: A Pilot Study (I9.012)

BACKGROUND: AD is associated with an increased incidence of epileptic seizures, and evidence from mouse models indicates that epileptiform activity can occur before any neuropathological or behavioral changes. This suggests that cortical irritability may represent an early biomarker of AD, especially during sleep when there is a higher prevalence of interictal epileptiform discharges compared to wakefulness in epileptic patients. The aim of this study is to investigate the presence of EEG abnormalities during sleep in cognitively normal elderly with or without neurodegenerative disease as evidenced by AD CSF biomarkers. DESIGN/METHODS: Cognitively normal elderly participants (n=21, CDR = 0) without sleep complaints were recruited from a study on aging at NYU School of Medicine. All participants underwent full-montage EEG recording for one night, reviewed by a clinical neurophysiologist for epileptiform discharges and abnormal slowing. CSF total tau (t-tau), phosphorylated tau (p-tau), and Abeta42 were analyzed using ELISA. CSF cutoff values were defined based on a separate dataset from 199 participants with or without AD (age range 60-80). RESULTS: 23.8[percnt] of the participants had spikes during sleep, 19[percnt] had frontotemporal slowing and 9.5[percnt] had mild generalized slowing. The likelihood of having abnormal EEG findings was approximately twice as high in participants with positive CSF biomarkers compared to individuals with negative CSF biomarkers (71.4[percnt] versus 35.7[percnt], respectively). With regards to absolute CSF biomarker levels, there was no difference in Abeta42 and t-tau levels, but there was a trend for higher p-tau levels in participants with abnormal EEGs (mean 47.2 pg/mL versus 42.5 pg/mL, p=.17). CONCLUSIONS: This pilot study shows that individuals with CSF biomarkers suggestive of preclinical AD have a higher incidence of EEG abnormalities during sleep than those without. Conversely, EEG abnormalities were moderately predictive of elevated p-tau levels.