Abstract
Background/Objectives: Mild cognitive impairment (MCI) is accompanied by olfactory dysfunction, and few interventions target shared chemosensory–cognitive mechanisms. We retrospectively examined whether a 5-week oxygen–ozone major autohemotherapy (MAH) cycle is associated with coupled improvements in olfactory and cognitive performance in adults with MCI. Methods: We analyzed 81 individuals with MCI who completed 10 MAH sessions (twice weekly) and 93 matched healthy controls. In the MCI group, olfactory function was measured before and after MAH using Sniffin’ Sticks® threshold–discrimination–identification (TDI) scores; global cognition was assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). We evaluated between-group and pre–post changes and used Spearman correlations to assess olfactory–cognitive coupling. Results: At baseline, MCI participants showed lower TDI and MoCA scores than controls and more hyposmia/anosmia. Following MAH, the proportion of normosmic patients increased from 32.1% to 50.6%, with fewer anosmic cases. TDI scores improved but remained lower than in controls. MMSE scores were unchanged, whereas MoCA total scores increased, with domain-level gains and a significant improvement in Language Repetition. TDI gains were modestly correlated with MoCA total and selected domain changes. Conclusions: In this retrospective cohort, MAH was associated with partial restoration improvements of olfactory function and improved cognitive performance. Correlated olfactory–cognitive changes were observed within the treated MCI group; however, causal attribution to O2–O3 MAH cannot be established without randomized, double-blind, sham-controlled trials with coupled olfactory–cognitive gains consistent with a shared, potentially modifiable substrate. Prospective randomized trials are needed to confirm efficacy and clinical utility.