Transcranial magnetic stimulation neurophysiology in patients with non-Alzheimer's neurodegenerative diseases: A systematic review and meta-analysis.

Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing NAD remains challenging due to the lack of established biomarkers. 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 NAD and healthy controls. Our meta-analyses indicated that TMS neurophysiological examinations revealed decreased glutamatergic function in patients with frontotemporal dementia (FTD) and decreased GABAergic function in patients with FTD, progressive supranuclear palsy, Huntington's disease, cortico-basal syndrome, and multiple system atrophy-parkinsonian type. In addition, decreased cholinergic function was found in dementia with Lewy body and vascular dementia. These results suggest the potential of TMS as an additional diagnostic tool to differentiate NAD.

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Declaration of interests SN has received grants from Japan Society for the Promotion of Science (18H02755, 22H03002), Japan Agency for Medical Research and development (AMED), Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Takeda Science Foundation, Uehara Memorial Foundation, Watanabe Foundation, and Osake-no-Kagaku Foundation within the past three years. SN has received an investigator-initiated clinical study grant from Asahi Quality & Innovations, Ltd. SN has received research support, manuscript fees or speaker’s honoraria from Sumitomo Pharma, Meiji- Seika Pharma, Otsuka Pharmaceutical, and MSD within the past three years. MM has received speaker’s honoraria from Byer Pharmaceutical, Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, Fuji Film RI Pharma, Hisamitsu Pharmaceutical, Janssen Pharmaceutical, Kyowa Pharmaceutical, Mochida Pharmaceutical, MSD, Mylan EPD, Nihon Medi-physics, Nippon Chemipher, Novartis Pharma, Ono Yakuhin, Otsuka Pharmaceutical, Pfizer, Santen Pharmaceutical, Shire Japan, Takeda Yakuhin, Tsumura, and Yoshitomi Yakuhin within the past three years. Also, he received grants from Daiichi Sankyo, Eisai, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi, and Tsumura within the past three years outside the submitted work. S.F. has received a Grant-in-Aid for Young Scientists B (16K16483) and Grants-in-Aid for Scientific Research B (20H04092) from JSPS and research grants from Keio University Academic Development Funds. All other authors declare that they have no conflicts of interest. YN has received a Grant-in-Aid for Scientific Research (B) (21H02813) from the Japan Society for the Promotion of Science (JSPS), research grants from Japan Agency for Medical Research and Development (AMED), investigator-initiated clinical study grants from Teijin Pharma Ltd. and Inter Reha Co., Ltd. He has also received a research grant from the Watanabe Foundation and Daiichi Sankyo Scholarship Donation Program. He has received speaker’s honoraria from Sumitomo Pharma Co., Ltd., Teijin Pharma Ltd., Takeda Pharmaceutical Co., Ltd., and Lundbeck Japan Co. Ltd., and Viatris Inc. within the past three years outside the submitted work. He also receives equipment-in-kind support for an investigator-initiated study from Magventure Inc., Inter Reha Co., Ltd., and Miyuki Giken Co., Ltd. The other co-authors declare no conflicts of interest.