Neurophysiological biomarkers using transcranial magnetic stimulation in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis

Yu Mimura; Hana Nishida; Shinichiro Nakajima; Sakiko Tsugawa; Shinji Morita; Kazunari Yoshida; Ryosuke Tarumi; Kamiyu Ogyu; Masataka Wada; Shin Kurose; Takahiro Miyazaki; Daniel M Blumberger; Zafiris J Daskalakis; Robert Chen; Masaru Mimura; Yoshihiro Noda

doi:10.1016/j.neubiorev.2020.12.003

Neurophysiological biomarkers using transcranial magnetic stimulation in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis

Neurosci Biobehav Rev. 2021 Feb:121:47-59. doi: 10.1016/j.neubiorev.2020.12.003. Epub 2020 Dec 8.

Authors

Affiliations

¹ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
² Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada. Electronic address: shinichiro_nakajima@hotmail.com.
³ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁴ Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Division of Neurology, Department of Medicine, University of Toronto, Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
⁶ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. Electronic address: yoshi-tms@keio.jp.

PMID: 33307047
DOI: 10.1016/j.neubiorev.2020.12.003

Abstract

Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with AD, mild cognitive impairment (MCI), and healthy controls (HC). Our meta-analyses indicated that RMT, SAI, SICI, and LICI were significantly lower in patients with AD, while ICF did not show a difference in patients with AD compared with HC. In patients with MCI, RMT and SAI were significantly lower than in HC. In conclusion, motor cortical excitability was increased, while cholinergic function was decreased in AD and MCI in comparison with HC and patients with AD had decreased GABAergic and glutamatergic functions compared with HC. Our results warrant further studies to differentiate AD, MCI, and HC, employing multimodal TMS neurophysiology.

Keywords: Alzheimer’s disease; Biomarker; ICF; LICI; Mild cognitive impairment; PAS; Plasticity; RMT; SAI; SICI; TMS.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Alzheimer Disease*
Biomarkers
Cognitive Dysfunction*
Evoked Potentials, Motor
Humans
Neural Inhibition
Neurophysiology
Transcranial Magnetic Stimulation

Substances

Biomarkers