# Olfactory and Cognitive Performance Improvement After Oxygen–Ozone Major Autohemotherapy in Mild Cognitive Impairment: A Retrospective Cohort Study

**Authors:** Alessandro Micarelli, Simona Mrakic-Sposta, Sandro Malacrida, Alessandra Vezzoli, Riccardo Xavier Micarelli, Beatrice Micarelli, Ivan Granito, Marco Alessandrini

PMC · DOI: 10.3390/neurolint18030041 · Neurology International · 2026-02-24

## TL;DR

A study found that oxygen–ozone therapy may improve smell and cognitive function in people with mild cognitive impairment, but more research is needed to confirm the effects.

## Contribution

The study explores a potential link between olfactory and cognitive improvements after oxygen–ozone therapy in mild cognitive impairment.

## Key findings

- Olfactory function improved in MCI patients after oxygen–ozone therapy, with increased normosmia rates.
- Cognitive performance, particularly language repetition, improved in MCI patients post-treatment.
- Olfactory and cognitive improvements were modestly correlated within the treated MCI group.

## 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.

## Linked entities

- **Chemicals:** oxygen–ozone (PubChem CID 131711318)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, DOCK3 (dedicator of cytokinesis 3) [NCBI Gene 1795] {aka MOCA, NEDIDHA, PBP}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, TAS2R62P (taste 2 receptor member 62, pseudogene) [NCBI Gene 338399] {aka PS1, T2R62, TAS2R62}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, GSTK1 (glutathione S-transferase kappa 1) [NCBI Gene 373156] {aka GST, GST 13-13, GST13, GST13-13, GSTK1-1, hGSTK1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}
- **Diseases:** , renal, (MESH:D006030), disorder (MESH:D009358), CKD (MESH:D012080), systemic or organ failure disorders (MESH:D009102), MAH (MESH:D004830), vascular dysregulation (MESH:D021081), vascular dysfunction (MESH:D002561), injury to (MESH:D014947), metabolic diseases (MESH:D008659), -throat (MESH:C538390), ischemic stroke (MESH:D002544), dementia (MESH:D003704), MCI (MESH:D060825), dysgeusia (MESH:D004408), cognitive frailty (MESH:D000073496), G6PD deficiency (MESH:D005955), microvascular dysfunction (MESH:D017566), executive and episodic memory deficits (MESH:D008569), CNS disorders (MESH:D002494), endocrinological disorders (MESH:D004700), COVID-19 (MESH:D000086382), OI (MESH:D000089083), chronic kidney disease (MESH:D051436), in lung (MESH:D008171), endothelial dysfunction (MESH:D014652), allergies (MESH:D004342), mitochondrial failure (MESH:D051437), airway inflammation (MESH:D007249), neurodegeneration (MESH:D019636), hyposmia (MESH:D000086582), central nervous system disorders (MESH:D002493), hyperthyroidism (MESH:D006980), amyloid (MESH:C000718787), Gastrointestinal/eating disturbances (MESH:D001068), Cognitive Impairment (MESH:D003072), Parkinson's disease (MESH:D010300), neuroinflammation (MESH:D000090862), drug/alcohol abuse (MESH:D019966), anosmic (MESH:D017436), olfactory decline (MESH:D000857), AD (MESH:D000544), neuro-psychiatric and cardiovascular disorders (MESH:D001523)
- **Chemicals:** O2 (MESH:D010100), O3 (MESH:D010126), glutamate (MESH:D018698), C13 urea (-), reactive oxygen species (MESH:D017382), nitric oxide (MESH:D009569), lipid (MESH:D008055), alcohol (MESH:D000438), PiB (MESH:C069442)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Helicobacter pylori (species) [taxon 210]

## Full text

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## Figures

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## References

88 references — full list in the complete paper: https://tomesphere.com/paper/PMC13028810/full.md

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Source: https://tomesphere.com/paper/PMC13028810