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(1) Background: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. Hydrogen gas (H 2 ) 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 H 2 treatment was conducted. (2) Methods: Eight patients with AD inhaled 3% H 2 gas for one hour twice daily for 6 months and then followed for 1 year without inhaling H 2 gas. The patients were clinically assessed using the Alzheimer's 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 H 2 treatment (-4.1) vs. untreated patients (+2.6). As assessed by DTI, H 2 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 H 2 treatment not only relieves temporary symptoms, but also has disease-modifying effects, despite its limitations.

pharmaceuticals

Therapeutic Inhalation of Hydrogen Gas for Alzheimer’s Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study