{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:09:08Z","timestamp":1791576548111,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>(1) Background: Alzheimer\u2019s disease (AD) is a progressive and fatal neurodegenerative disorder. Hydrogen gas (H2) is a therapeutic medical gas with multiple functions such as anti-oxidant, anti-inflammation, anti-cell death, and the stimulation of energy metabolism. To develop a disease-modifying treatment for AD through multifactorial mechanisms, an open label pilot study on H2 treatment was conducted. (2) Methods: Eight patients with AD inhaled 3% H2 gas for one hour twice daily for 6 months and then followed for 1 year without inhaling H2 gas. The patients were clinically assessed using the Alzheimer\u2019s Disease Assessment Scale-cognitive subscale (ADAS-cog). To objectively assess the neuron integrity, diffusion tensor imaging (DTI) with advanced magnetic resonance imaging (MRI) was applied to neuron bundles passing through the hippocampus. (3) Results: The mean individual ADAS-cog change showed significant improvement after 6 months of H2 treatment (\u22124.1) vs. untreated patients (+2.6). As assessed by DTI, H2 treatment significantly improved the integrity of neurons passing through the hippocampus vs. the initial stage. The improvement by ADAS-cog and DTI assessments were maintained during the follow-up after 6 months (significantly) or 1 year (non-significantly). (4) Conclusions: This study suggests that H2 treatment not only relieves temporary symptoms, but also has disease-modifying effects, despite its limitations.<\/jats:p>","DOI":"10.3390\/ph16030434","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T04:04:00Z","timestamp":1678680240000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Therapeutic Inhalation of Hydrogen Gas for Alzheimer\u2019s Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Hirohisa","family":"Ono","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery and Neurology, Nishijima Hospital, Ohoka, 2835-7, Numazu City 410-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoji","family":"Nishijima","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and Neurology, Nishijima Hospital, Ohoka, 2835-7, Numazu City 410-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2539-470X","authenticated-orcid":false,"given":"Shigeo","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Neurology Medicine, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.2174\/1568026618666180112161024","article-title":"Alzheimer\u2019s Disease: A Systemic Review of Substantial Therapeutic Targets and the Leading Multi-functional Molecules","volume":"17","author":"Umar","year":"2018","journal-title":"Curr. 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