Abnormalities of cortical neural synchronization mechanisms in subjects with mild cognitive impairment due to Alzheimer's disease and epileptiform‐like signatures

• Published in: Alzheimer's & dementia Vol. 16
• Main Authors: Percio, Claudio Del, Noce, Giuseppe, Bonaventura, Carlo Di, Lizio, Roberta, Soricelli, Andrea, Ferri, Raffaele, Nobili, Flavio Mariano, Famà, Francesco, Palma, Eleonora, Cifelli, Pierangelo, Marizzoni, Moira, Frisoni, Giovanni B, Babiloni, Claudio
• Format: Journal Article
• Language: English
• Published: 01.12.2020
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.045825

Background Previous evidence has shown that Alzheimer’s disease (AD) patients exhibited an increased risk of overt epileptic seizures or subclinical, non‐convulsive, epileptiform‐like electroencephalographic (EEG) signatures (i.e., spike‐sharp wave discharges, giant spikes, etc.) due to temporal and frontal lobe dysfunctions and aberrant cortical neural synchronization. In the present study, cortical sources of resting state eyes‐closed EEG (rsEEG) rhythms were estimated in patients with amnesic mild cognitive impairment due to AD (ADMCI), using normal elderly (Nold) and AD patients with dementia (ADD) as controls. The hypothesis was that rsEEG sources may be more abnormal in ADMCI with than without epileptiform‐like EEG signatures. Method Clinical and rsEEG data in 35 ADD, 50 ADMCI, and 35 Nold subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini Mental State Evaluation (MMSE) score was matched between the ADMCI with and without epileptiform‐like EEG signatures (i.e., spike‐sharp wave discharges, giant spikes, etc.). No subject had received a clinical diagnosis of epilepsy. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Result Frontal and temporal delta source activities were more abnormal in the ADMCI patients with epileptiform‐like EEG signatures (N = 13; 26%; ADMCI‐ELES) and ADD than the control ADMCI patients (N= 37; ADMCI‐noELES; Figure 1). This effect may not depend on sleep onset or epileptiform‐like EEG signatures as “biological artifacts” in the EEG signal, because of the present source analysis was performed from rsEEG epochs free from those signatures. Conclusion The present findings suggest that in MCI patients, AD neuropathology may derange neurophysiological low‐frequency (i.e. delta) oscillatory mechanisms underpinning cortical arousal and quiet vigilance, and such derangement may be more pronounced in frontal and temporal cortical regions in ADMCI patients characterized by epileptiform EEG signatures. Future investigations should cross‐validate the present findings by a longitudinal prospective study testing. We predict that ADMCI patients with those delta source and epileptiform‐like EEG signatures may develop a fast disease progression.