Main Article Content
Introduction: Molecular hydrogen (H2) has emerged as a therapeutic medical gas that exerts multiple functions. H2 inhalation has been approved as safe, and some clinical studies showed that it effectively improved conditions of patients with a variety of disorders such as stroke, heart infarction, chronic obstructive pulmonary disease, cancer, and COVID-19. Urinary and fecal incontinences are unavoidable symptoms of advanced Alzheimer's disease (AD) dementia. In particular, fecal incontinence increases the level of confusion for patients and caretakers suffer from increased workloads.
Materials and Methods: To assess the integrity of the neurons related to AD, the bundles of neurons passing through the hippocampus were visualized by modified diffusion tensor imaging (DTI) technology using advanced magnetic resonance imaging (MRI)
Results: A 79-year-old woman with advanced AD continued to inhale 3% H2 gas containing 21% oxygen twice daily for 1 hour and maintained clinical observations for 2 years. After the long period of inhalation of H2 gas, the patient went to the bathroom by herself for adequate excretion. She remained to be able to go to the bathroom for her bowel movements in time, afterwards. After the long-term inhalation of H2 gas, her MRI of the brain to generate DTI images with an anisotropic (FA) value of 0.2 (FA = 0.2) showed improved integrity of the hippocampal neurons along with these clinical improvements.
Conclusion: This case report casts the question on the current understanding that the advanced and severe AD patients will never improve.
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
2. Sang Z, Wang K, Dong J, Tang L. Alzheimer's disease: Updated multi-targets therapeutics are in clinical and in progress. Eur J Med Chem. 2022; 238: 114464. ISNN: 2768-6698 (Electronic) 2768-6698 (Linking) DOI: 10.31083/j.fbl2705146
3. Honig LS, Mayeux R. Natural history of Alzheimer's disease. Aging (Milano). 2001; 13(3): 171-82. ISNN: 0394-9532 (Print) 0394-9532 (Linking) DOI: 10.1007/BF03351476
4. Warshaw GA. New perspectives in the management of Alzheimer's disease. Am Fam Physician. 1990; 42(5 Suppl): 41S-7S. ISSN: 0002-838X (Print) 0002-838X (Linking) PMID: 2239649
5. AlAmeel T, Andrew MK, MacKnight C. The association of fecal incontinence with institutionalization and mortality in older adults. Am J Gastroenterol. 2010; 105(8): 1830-4. ISSN: 1572-0241 (Electronic) 0002-9270 (Linking) DOI: 10.1038/ajg.2010.77
6. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007; 13(6): 688-94. ISSN: 1078-8956 (Print) 1078-8956 (Linking) DOI: 10.1038/nm1577
7. Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine. Pharmacol Ther. 2014; 144(1): 1-11. ISSN: 1879-016X (Electronic) 0163-7258 (Linking) DOI: 10.1016/j.pharmthera.2014.04.006
8. Ohta S. Development of Hydrogen Medicine and Biology: Potential for Various Applications in Diverse Fields. Curr Pharm Des. 2021; 27(5): 583-4. ISSN: 1873-4286 (Electronic) 1381-6128 (Linking) and DOI: 10.2174/138161282705210211144515
9. Ono H, Nishijima Y, Ohta S, Sakamoto M, Kinone K, Horikosi T, et al. Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection. J Stroke Cerebrovasc Dis. 2017; 26(11): 2587-94. ISSN: 1532-8511 (Electronic) 1052-3057 (Linking) DOI: 10.1016/j.jstrokecerebrovasdis.2017.06.012
10. Katsumata Y, Sano F, Abe T, Tamura T, Fujisawa T, Shiraishi Y, et al. The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction- First Pilot Study in Humans. Circ J. 2017; 81(7): 940-7. ISSN: 1347-4820 (Electronic) 1346-9843 (Linking) DOI: 10.1253/circj.CJ-17-0105
11. Zheng ZG, Sun WZ, Hu JY, Jie ZJ, Xu JF, Cao J, et al. Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial. Respir Res. 2021; 22(1): 149. ISSN: 1465-993X (Electronic) 1465-9921 (Linking) DOI: 10.1186/s12931-021-01740-w
12. Akagi J, Baba H. Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis. Oncol Rep. 2019; 41(1): 301-11. ISSN: 1791-2431 (Electronic) 1021-335X (Linking) DOI: 10.3892/or.2018.6841
13. Botek M, Krejci J, Valenta M, McKune A, Sladeckova B, Konecny P, et al. Molecular Hydrogen Positively Affects Physical and Respiratory Function in Acute Post-COVID-19 Patients: A New Perspective in Rehabilitation. Int J Environ Res Public Health. 2022; 19(4): 1992. ISSN: 1660-4601 (Electronic) 1660-4601 (Linking) doi: 10.3390/ijerph19041992.1992
14. Luo P, Ding Y, He Y, Chen D, He Q, Huang Z, et al. Hydrogen-oxygen therapy alleviates clinical symptoms in twelve patients hospitalized with COVID-19: A retrospective study of medical records. Medicine (Baltimore). 2022; 101(9): e27759. ISSN: 1536-5964 (Electronic) 0025-7974 (Linking) DOI: 10.1097/MD.0000000000027759
15. Cole AR, Sperotto F, DiNardo JA, Carlisle S, Rivkin MJ, Sleeper LA, et al. Safety of Prolonged Inhalation of Hydrogen Gas in Air in Healthy Adults. Crit Care Explor. 2021; 3(10): e543. ISSN: 2639-8028 (Electronic) 2639-8028 (Linking) DOI: 10.1097/CCE.0000000000000543
16. Nishimaki K, Asada T, Ohsawa I, Nakajima E, Ikejima C, Yokota T, et al. Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment. Curr Alzheimer Res. 2018; 15(5): 482-92. ISSN: 1875-5828 (Electronic) 1567-2050 (Linking) DOI: 10.2174/1567205014666171106145017
17. Chua TC, Wen W, Slavin MJ, Sachdev PS. Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review. Curr Opin Neurol. 2008; 21(1): 83-92. ISSN: 1350-7540 (Print) 1350-7540 (Linking) DOI: 10.1097/WCO.0b013e3282f4594b
18. Amlien IK, Fjell AM. Diffusion tensor imaging of white matter degeneration in Alzheimer's disease and mild cognitive impairment. Neuroscience. 2014; 276: 206-15. ISSN: 1873-7544 (Electronic) 0306-4522 (Linking) DOI: 10.1016/j.neuroscience.2014.02.017
19. Toniolo S, Serra L, Olivito G, Caltagirone C, Mercuri NB, Marra C, et al. Cerebellar White Matter Disruption in Alzheimer's Disease Patients: A Diffusion Tensor Imaging Study. J Alzheimers Dis. 2020; 74(2): 615-24. ISNN: 1875-8908 (Electronic) 1387-2877 (Linking) DOI: 10.3233/JAD-191125
20. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984; 141(11): 1356-64. ISSN: 0002-953X (Print) 0002-953X (Linking) DOI: 10.1176/ajp.141.11.1356
21. Ono H, Nishijima Y, Sakamoto M, Hirikosi T, Tamaki M, Oishi W, et al. Pilot study on Therapeutic Inhalation of hydrogen gas for improving patients with Alzheimer's disease assessed by cognitive subscale scores and magnetic resonance diffusion tensor umaging. Int J Alzheimers & Neuro Disorder. 2018; 1(1): 004. https://bioaccent.org/alzheimers-neurological/alzheimers-neurological04.pdf
22. Wood KC, Gladwin MT. The hydrogen highway to reperfusion therapy. Nat Med. 2007; 13(6): 673-4. ISSN: 1078-8956 (Print) 1078-8956 (Linking) DOI: 10.1038/nm0607-673
23. Iuchi K, Imoto A, Kamimura N, Nishimaki K, Ichimiya H, Yokota T, et al. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep. 2016; 6: 18971. ISSN: 2045-2322 (Electronic) 2045-2322 (Linking) DOI: 10.1038/srep18971
24. Ohta S. Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions. Curr Pharm Des. 2021; 27(5): 595-609. ISSN: 1873-4286 (Electronic) 1381-6128 (Linking) DOI: 10.2174/1381612826666200806101137
25. Abdul HM, Sama MA, Furman JL, Mathis DM, Beckett TL, Weidner AM, et al. Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin/NFAT signaling. J Neurosci. 2009; 29(41): 12957-69. ISSN: 1529-2401 (Electronic) 0270-6474 (Linking) DOI: 10.1523/JNEUROSCI.1064-09.2009
26. Hudry E, Wu HY, Arbel-Ornath M, Hashimoto T, Matsouaka R, Fan Z, et al. Inhibition of the NFAT pathway alleviates amyloid beta neurotoxicity in a mouse model of Alzheimer's disease. J Neurosci. 2012; 32(9): 3176-92. ISSN: 1529-2401 (Electronic) 0270-6474 (Linking) DOI: 10.1523/JNEUROSCI.6439-11.2012