Alzheimer’s Disease with Epileptiform EEG Activity: Abnormal Cortical Sources of Resting State Delta Rhythms in Patients with Amnesic Mild Cognitive Impairment

Article type: Research Article

Authors: Babiloni, Claudio^{a; b; *} | Noce, Giuseppe^c | Di Bonaventura, Carlo^d | Lizio, Roberta^c | Eldellaa, Ali^a | Tucci, Federico^a | Salamone, Enrico M.^{a; d} | Ferri, Raffaele^e | Soricelli, Andrea^{c; f} | Nobili, Flavio^{g; h} | Famà, Francesco^g | Arnaldi, Dario^g | Palma, Eleonora^{a; i} | Cifelli, Pierangelo^{j; k} | Marizzoni, Moira^l | Stocchi, Fabrizio^m | Bruno, Giuseppeⁿ | Di Gennaro, Giancarlo^j | Frisoni, Giovanni B.^{l; o} | Del Percio, Claudio^a

Affiliations: [a] Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Rome, Italy | [b] Hospital San Raffaele Cassino, Cassino (FR), Italy | [c] IRCCS Synlab SDN, Naples, Italy | [d] Epilepsy Unit, Department of Neurosciences/Mental Health, Sapienza University of Rome, Rome, Italy | [e] Oasi Research Institute – IRCCS, Troina, Italy | [f] Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy | [g] Clinical Neurology, IRCCS Hospital Policlinico San Martino, Genoa, Italy | [h] Department of Neuroscience (DiNOGMI), University of Genoa, Genoa, Italy | [i] Pasteur Institute-Cenci Bolognetti Foundation, Rome, Italy | [j] IRCCS Neuromed, Pozzilli, (IS), Italy | [k] Department of Applied and Biotechnological Clinical Sciences, University of L’Aquila, L’Aquila, Italy | [l] Laboratory of Alzheimer’s Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [m] IRCCS San Raffaele Roma, Rome, Italy | [n] Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy | [o] Memory Clinic and LANVIE – Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland

Correspondence: [*] Correspondence to: Prof. Claudio Babiloni, PhD, Department of Physiology and Pharmacology “V. Erspamer”,Sapienza University of Rome, P. le A. Moro 5, 00185, Rome, Italy. Tel.: +39 0649910989; E-mail: [email protected].

Abstract: Background:Patients with amnesic mild cognitive impairment due to Alzheimer’s disease (ADMCI) typically show a “slowing” of cortical resting-state eyes-closed electroencephalographic (rsEEG) rhythms. Some of them also show subclinical, non-convulsive, and epileptiform EEG activity (EEA) with an unclear relationship with that “slowing.” Objective:Here we tested the hypothesis that the “slowing” of rsEEG rhythms is related to EEA in ADMCI patients. Methods:Clinical and instrumental datasets in 62 ADMCI patients and 38 normal elderly (Nold) subjects were available in a national archive. No participant had received a clinical diagnosis of epilepsy. The eLORETA freeware estimated rsEEG cortical sources. The area under the receiver operating characteristic curve (AUROCC) indexed the accuracy of eLORETA solutions in the classification between ADMCI-EEA and ADMCI-noEEA individuals. Results:EEA was observed in 15% (N = 8) of the ADMCI patients. The ADMCI-EEA group showed: 1) more abnormal Aβ42 levels in the cerebrospinal fluid as compared to the ADMCI-noEEA group and 2) higher temporal and occipital delta (<4 Hz) rsEEG source activities as compared to the ADMCI-noEEA and Nold groups. Those source activities showed moderate accuracy (AUROCC = 0.70–0.75) in the discrimination between ADMCI-noEEA versus ADMCI-EEA individuals. Conclusion:It can be speculated that in ADMCI-EEA patients, AD-related amyloid neuropathology may be related to an over-excitation in neurophysiological low-frequency (delta) oscillatory mechanisms underpinning cortical arousal and quiet vigilance.

Keywords: Epileptiform EEG activity, exact low-resolution brain electromagnetic source tomography, mild cognitive impairment due to Alzheimer’s disease, resting state electroencephalographic rhythms

DOI: 10.3233/JAD-220442

Journal: Journal of Alzheimer's Disease, vol. 88, no. 3, pp. 903-931, 2022