RCT 2020
From the library

Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial

Hadanny A, Daniel-Kotovsky M, Suzin G, Boussi-Gross R, Catalogna M, Dagan K, Lang E, Finci S, Polak N, Fishlev G, Korin C, Tzabari A, Shabi S, Sasson E, Efrati S

Aging (Albany NY) n = 63 2 ATA 60 sessions
Plain English

Hadanny et al. (2020, Aging) is the cornerstone trial for HBOT as a cognitive-enhancement intervention in healthy older adults — distinct from injury-recovery use cases like TBI or stroke. What the trial measured. Two primary outcome categories: standardized neuropsychological testing (attention, information processing speed, executive function including set-shifting, memory) and objective brain imaging (perfusion MRI for cerebral blood flow, voxel-based analysis). The trial deliberately paired cognitive testing with imaging to address the chronic concern that cognitive trials are vulnerable to practice effects and self-report bias. Who was studied. Sixty-three healthy adults aged over 64 years (mean older), randomized to active HBOT (n=33) or control (n=30) for three months. Critically, the cohort excluded participants with prior brain pathology, mild cognitive impairment, or pathological cognitive decline — this is a healthy-aging trial, not a disease-recovery trial. The exclusion is what distinguishes Cognitive Performance from the TBI page on the Saturate site. Protocol parameters. Sixty daily HBOT sessions at 2.0 ATA, 100% oxygen with 5-minute air breaks every 20 minutes, 90 minutes per session, 5 days per week, over three months. The 5-minute air-break design was deliberately included to engage the 'oxygen paradox' — the hyperoxic-hypoxic fluctuation that drives the regenerative response. This air-break design has since become standard for cognitive HBOT protocols. Results. The group-by-time interaction in global cognitive function was statistically significant (p=0.0017). The largest individual effect sizes were attention (0.745) and information processing speed (0.788) — by Cohen convention, both are large effects. Set-shifting (a subset of executive function) also improved significantly. The HBOT group showed positive change while the control group showed slight deterioration over the same window — a consistent, directional pattern. Voxel-based perfusion MRI confirmed cerebral blood flow increases in the right superior medial frontal gyrus (BA10), bilateral supplementary motor area (BA6), middle frontal gyrus, and superior frontal gyrus — exactly the prefrontal regions where age-related decline is most pronounced. Limitations. Sample size (n=63) is modest. Cohort was deliberately healthy older adults — generalizability to younger healthy adults is unclear because younger cohorts have less room to improve on the same measures (ceiling effect). Long-term durability beyond the immediate post-protocol window was not the primary focus; the broader Hachmo 2020 / Hachmo 2021 / Hadanny 2024 trial program addresses durability separately. What it means in practice. The Hadanny 2020 protocol — 60 sessions at 2.0 ATA with 5-minute air breaks, 90-minute sessions, 5 days per week — is the directly-cited reference for the Cognitive Performance condition page. Cognitive enhancement is not an FDA-approved HBOT indication, so US insurance does not cover it; most users pay out of pocket at clinical chambers. How it relates to other indexed trials. Hadanny 2020 is part of the same Israeli research-program cohort that produced Hachmo 2020 (telomere/senescent-cell clearance) and Hachmo 2021 (skin-biopsy substudy). The three papers together form the strongest single-cohort longevity evidence base in HBOT — cognitive, cellular, and dermal endpoints all moving in the same direction with the same protocol. The Marcinkowska 2022 systematic review of 42 cognitive-HBOT studies provides the broader cross-disorder context. Source: PubMed PMID 32589613.

Key findings

What the trial documented.

  • Significant group-by-time interaction in global cognitive function (p=0.0017)
  • Most striking improvements: attention (effect size 0.745) and information processing speed (effect size 0.788)
  • Significant improvement in set-shifting (subset of executive function)
  • Voxel-based perfusion MRI confirmed cerebral blood flow increases in prefrontal cortex regions

Hadanny et al. (2020, Aging) is the cornerstone trial for HBOT as a cognitive-enhancement intervention in healthy older adults — distinct from injury-recovery use cases like TBI or stroke.

What the trial measured. Two primary outcome categories: standardized neuropsychological testing (attention, information processing speed, executive function including set-shifting, memory) and objective brain imaging (perfusion MRI for cerebral blood flow, voxel-based analysis). The trial deliberately paired cognitive testing with imaging to address the chronic concern that cognitive trials are vulnerable to practice effects and self-report bias.

Who was studied. Sixty-three healthy adults aged over 64 years (mean older), randomized to active HBOT (n=33) or control (n=30) for three months. Critically, the cohort excluded participants with prior brain pathology, mild cognitive impairment, or pathological cognitive decline — this is a healthy-aging trial, not a disease-recovery trial. The exclusion is what distinguishes Cognitive Performance from the TBI page on the Saturate site.

Protocol parameters. Sixty daily HBOT sessions at 2.0 ATA, 100% oxygen with 5-minute air breaks every 20 minutes, 90 minutes per session, 5 days per week, over three months. The 5-minute air-break design was deliberately included to engage the ‘oxygen paradox’ — the hyperoxic-hypoxic fluctuation that drives the regenerative response. This air-break design has since become standard for cognitive HBOT protocols.

Results. The group-by-time interaction in global cognitive function was statistically significant (p=0.0017). The largest individual effect sizes were attention (0.745) and information processing speed (0.788) — by Cohen convention, both are large effects. Set-shifting (a subset of executive function) also improved significantly. The HBOT group showed positive change while the control group showed slight deterioration over the same window — a consistent, directional pattern. Voxel-based perfusion MRI confirmed cerebral blood flow increases in the right superior medial frontal gyrus (BA10), bilateral supplementary motor area (BA6), middle frontal gyrus, and superior frontal gyrus — exactly the prefrontal regions where age-related decline is most pronounced.

Limitations. Sample size (n=63) is modest. Cohort was deliberately healthy older adults — generalizability to younger healthy adults is unclear because younger cohorts have less room to improve on the same measures (ceiling effect). Long-term durability beyond the immediate post-protocol window was not the primary focus; the broader Hachmo 2020 / Hachmo 2021 / Hadanny 2024 trial program addresses durability separately.

What it means in practice. The Hadanny 2020 protocol — 60 sessions at 2.0 ATA with 5-minute air breaks, 90-minute sessions, 5 days per week — is the directly-cited reference for the Cognitive Performance condition page. Cognitive enhancement is not an FDA-approved HBOT indication, so US insurance does not cover it; most users pay out of pocket at clinical chambers.

How it relates to other indexed trials. Hadanny 2020 is part of the same Israeli research-program cohort that produced Hachmo 2020 (telomere/senescent-cell clearance) and Hachmo 2021 (skin-biopsy substudy). The three papers together form the strongest single-cohort longevity evidence base in HBOT — cognitive, cellular, and dermal endpoints all moving in the same direction with the same protocol. The Marcinkowska 2022 systematic review of 42 cognitive-HBOT studies provides the broader cross-disorder context.

Source: PubMed PMID 32589613.

Protocol used

2.0 ATA, 100% oxygen with 5-minute air breaks every 20 minutes, 90-minute sessions, 5 days/week for 60 sessions over 3 months

Full citation

Hadanny A, Daniel-Kotovsky M, Suzin G, Boussi-Gross R, Catalogna M, Dagan K, Lang E, Finci S, Polak N, Fishlev G, Korin C, Tzabari A, Shabi S, Sasson E, Efrati S. Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial. Aging (Albany NY). 2020.