Abstract
Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer's disease (AD), despite a surge in recent validated evidence. This position paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity, reflecting thalamocortical and corticocortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies.
| Original language | English |
|---|---|
| Pages (from-to) | 58-73 |
| Number of pages | 16 |
| Journal | Neurobiology of Aging |
| Volume | 85 |
| Early online date | 19 Sept 2019 |
| DOIs | |
| Publication status | Published - 31 Jan 2020 |
Funding
Dr Harald Hampel serves as the senior associate editor for the Journal Alzheimer's & Dementia; he received lecture fees from Biogen and Roche, research grants from Pfizer, Avid, and MSD Avenir (paid to the institution), travel funding from Functional Neuromodulation, Axovant, Eli Lilly and Company, Takeda and Zinfandel, GE-Healthcare, and Oryzon Genomics, consultancy fees from Jung Diagnostics, Cytox Ltd, Axovant, Anavex, Takeda and Zinfandel, GE Healthcare, Oryzon Genomics, and Functional Neuromodulation and participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eli Lilly and company, Cytox Ltd, GE Healthcare, Takeda and Zinfandel, Oryzon Genomics, and Roche Diagnostics. This position paper is endorsed by the Electrophysiology Professional Interest Area (EPIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The authors thank the Executive Steering Committee of EPIA for their commitment to the production of this manuscript. Dr Fernando Lopes da Silva passed away due to health problems (January 24, 1935 to May 7, 2019). Until the end of his life, he had been working on the development of EEG science and its application in Clinical Neurophysiology. He leaves to all us an invaluable scientific legacy in the Science of Brain Rhythms and Human Cognition. He also leaves a permanent reminder of scientific passion, academic soul, and social responsibility to all fortunate people who met and knew him during his intense life. Dr Claudio Babiloni, Dr Stefan Teipel, and Dr Emmanuel Ifeachor are supported by European Committee (H2020-EU.1.3.1.H2020-MSCA-ITN-ETN-2016 project with short title “BBDiag”). Dr Fiona Randall is a full-time employee of 41. Vertex Pharmaceuticals Incorporated. Dr Pim Drinkenburg is a full-time employee and holds shares/options of Janssen Pharmaceutica NV, Pharmaceutical Companies of Johnson & Johnson. Dr Harald Hampel is supported by the AXA Research Fund , the “ Fondation partenariale Sorbonne Université ” and the “ Fondation pour la Recherche sur Alzheimer ,” Paris, France. Ce travail a bénéficié d'une aide de l’Etat “Investissements d'avenir” ANR-10-IAIHU-06. The research leading to these results has received funding from the program “ Investissements d'avenir ” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6). This publication benefited from the support of the Program “PHOENIX” led by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer. Dr Roberta Lizio gave her contribution to this paper with the support of “Ricerca Corrente” funds of Italian Ministry of Health . Appendix
Keywords
- Alzheimer's disease (AD)
- electroencephalography and magnetoencephalography (EEG and MEG)
- event-related potentials and magnetic fields
- preclinical and clinical research
- resting-state condition
- The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART)