Inhaled hydrogen therapy alleviates cognitive impairment in individuals with mild Alzheimer’s disease by optimising peripheral immune homeostasis: a clinical evaluation

This study aimed to investigate the effect of a hydrogen inhalation intervention on cognitive function in patients with mild Alzheimer’s disease (AD) and to analyse the potential mechanism from the perspective of neuroimmunological regulation, thus providing new clinical evidence regarding the non-pharmacological treatment of AD. Eighty patients with mild AD who visited our hospital between February 2024 and June 2025 were selected as study subjects and randomly divided into control and hydrogen inhalation intervention (treatment) groups ( n = 40 per group). The double-blind principle was followed in both the treatment and control groups during the cognitive function assessment phase. The control group received routine clinical nursing care and rehabilitation training, while the intervention group received hydrogen inhalation therapy five times a week for 12 weeks, in addition to routine care. The Montreal Cognitive Assessment (MoCA) was used to evaluate the patients’ cognitive level. Flow cytometry was used to detect the distribution of peripheral blood lymphocyte subsets, and a dry fluorescence immunoassay was used to detect changes in human phosphorylated tau-181 protein (P-tau-181) concentrations. After the 12-week intervention, the MoCA scores of patients in the treatment group were significantly improved relative to the within-group baseline values and significantly higher than those in the control group at the same time point. Regarding immune indicators, the proportion of peripheral blood CD4 + T lymphocytes and the CD4 + /CD8 + T lymphocyte ratio were significantly lower in the treatment group than in the control group. Compared with the control group, the treatment group had a higher proportion of CD8 + T lymphocytes and a lower concentration of P-tau-181; both differences were statistically significant. Correlation analysis showed that the improvement in cognitive scores in the treatment group was significantly correlated with the trends of some of the above-mentioned immune indicators. Furthermore, the MoCA score in the treatment group was negatively correlated with the peripheral blood P-tau-181 concentration. Receiver operating characteristic curve analysis revealed that the inhaled hydrogen therapy intervention partially improved the proportion of peripheral blood CD4 + T lymphocytes in patients. Inhaled hydrogen therapy can effectively improve cognitive function and significantly reduce AD-related peripheral blood neuroimmunological markers in patients with mild AD. This treatment was found to yield good compliance among patients with mild AD when used as an adjunctive treatment, indicating broad prospects for clinical adjunctive applications.