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Brain

Cognitive ageing

Randomised trials with healthy older adults have measured attention, processing speed and brain blood flow before and after a course of hyperbaric oxygen sessions, and reported improvements in the treated group alongside changes in blood-cell markers of ageing.

Evidence so far
Early
Reading timeAbout 12 minutes

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Why this is being studied

Cognitive ageing is the gradual slowing of attention, processing speed and memory that happens in healthy people as they get older, in step with reduced blood flow to frontal brain regions and less efficient energy production in cells. Hyperbaric oxygen is being studied in this context because intermittent high oxygen appears to stimulate small-vessel growth, mitochondrial renewal and other repair pathways, and early trials have measured changes in brain perfusion, exercise capacity and cellular ageing markers. The evidence so far comes mostly from one research group, with small samples and no sham control.

Where the evidence stands

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The mechanism

What is going on, and why this might help

What is going on in the body

As the brain ages, cerebral blood flow gradually declines, the density of small vessels falls, and the blood-brain barrier becomes more permeable. Mitochondria become less efficient, low-grade inflammation rises (sometimes called 'inflammageing'), and cells accumulate senescent features and shortened telomeres. White-matter tracts that connect brain regions lose integrity. None of these changes alone causes dementia, but together they slow processing speed, attention and memory retrieval, and they set the stage for vascular cognitive impairment.

Where oxygen comes in

The rationale here rests mostly on vascular and cellular ageing biology. Hyperbaric oxygen delivers oxygen in plasma to regions with reduced capillary density, and in animal models induces angiogenesis via VEGF and HIF-1α signalling, increases cerebral blood flow and improves mitochondrial respiration. The hyperoxic-hypoxic paradox (Hadanny and Efrati 2020) proposes that the intermittent nature of sessions triggers regenerative pathways ordinarily switched on by hypoxia, including stem-cell mobilisation (Thom 2006). Anti-inflammatory effects on TNF-α and IL-6 are relevant to inflammageing. Small human studies in older adults have reported increased telomere length and reduced senescent T-cells in blood, and perfusion MRI changes alongside improvements on cognitive testing, which are consistent with these mechanisms but remain early findings.

How solid is this

Angiogenic and anti-inflammatory mechanisms are well established in animal models and in clinical wound and radiation work. Application to healthy cognitive ageing rests on one randomised trial in older adults (Hadanny et al. 2020) and a small telomere study (Hachmo et al. 2020), both from a single group and without long-term follow-up. This should be read as promising but preliminary. Key references: Hadanny and Efrati 2020; Hachmo et al. 2020.

Explainer illustration

The studies

Every study is laid out the same way: what the researchers wanted to find out, who took part, what they actually did, what they found, why it might work and where the limits are. No jargon, and a link to the original if you want to read it yourself.

Each study is laid out the same way: what the researchers asked, who took part, what they did, what they found, why it might work, and where the limits are. The clinician layer at the end of each one carries the numbers.

Paper 1

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

Hadanny et al. · Aging · 2020 · randomised controlled trial, n=63

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What they asked

Healthy people lose a little processing speed, attention and memory as they age, and blood flow to parts of the brain declines in parallel. This trial asked whether a three-month course of hyperbaric oxygen could improve cognitive performance in healthy older adults who had no diagnosed cognitive problem, and whether any improvement matched changes in brain blood flow on MRI.

Who took part

Seventy community-dwelling adults over 64 enrolled and 63 completed the study (30 oxygen, 33 control). Average age was about 70. All were independent, without dementia or mild cognitive impairment, without recent heart or stroke events, non-smokers, and without lung disease or recent hyperbaric treatment. By chance the oxygen group was about two years older on average.

What they did

The oxygen group breathed 100 per cent oxygen at 2 ATA for 90 minutes with a five-minute air break every 20 minutes, daily, five days a week, for 60 sessions over three months. The control group carried on with normal life and received no intervention; both groups were asked not to change their lifestyle, diet or medication and this was monitored. Cognition was tested with a computerised battery using alternate test forms to limit practice effects, and cerebral blood flow was measured with perfusion MRI, before and one to two weeks after the course. The people scoring the tests were blinded to group; the participants were not.

What they found

The oxygen group improved more than controls on the overall cognitive score, with a large net effect. The clearest gains were in attention, information processing speed and executive function (set shifting), with smaller but significant improvements in memory and verbal fluency. Perfusion MRI showed increased blood flow in several frontal regions and one parietal region in the oxygen group compared with controls, but no difference in whole-brain blood flow. Increases in blood flow in specific frontal areas correlated modestly with improvements in memory and attention.

Why it might work

The authors' explanation is that age-related cognitive slowing partly reflects reduced blood supply and mitochondrial efficiency in frontal circuits that support attention and speed. Repeated cycles of high oxygen followed by normal air seem to be read by cells as a relative shortage of oxygen, triggering the growth of new small vessels and other repair processes, which would fit with the regional increases in blood flow seen here.

Limits

There was no sham chamber and participants knew which group they were in, so expectation and the experience of a daily structured routine could contribute. Sixty-three completers is a modest sample. Follow-up was only one to two weeks after treatment, so we do not know how long any benefit lasts. Funding came from a neuroscience research network; several authors work for, and one holds shares in, a commercial hyperbaric company, which is declared.

Paper 2

Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial

Hachmo et al. · Aging · 2020 · prospective trial, n=35

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What they asked

Two of the most widely used laboratory markers of cellular ageing are telomere length (the protective caps on chromosomes that shorten with each cell division) and the proportion of senescent cells (cells that have stopped dividing but linger and secrete inflammatory signals). This study asked whether a course of hyperbaric oxygen changes these markers in the blood cells of healthy older adults.

Who took part

Thirty-five healthy adults over 64 enrolled and 30 provided baseline samples. Because of laboratory quality thresholds, 26 people were included in the telomere analysis and 20 in the senescent cell analysis. Average age was about 68, roughly half were men. There was no control group; everyone received treatment.

What they did

Participants completed 60 daily sessions, five days a week over three months, breathing 100 per cent oxygen at 2 ATA for 90 minutes with five-minute air breaks every 20 minutes. Blood was drawn at baseline, after the 30th session, after the 60th session, and one to two weeks after the course. Telomere length and senescence markers were measured separately in different immune cell types (B cells, helper T cells, cytotoxic T cells and natural killer cells) rather than in pooled blood cells. Participants were asked to keep diet, exercise and medication unchanged.

What they found

Telomere length increased in all four cell types, by roughly 20 to 38 per cent by the end of the study, with the largest and most consistent change in B cells. Senescent cell proportions fell, most clearly in helper T cells (down about 37 per cent after the course) and cytotoxic T cells (down about 10 per cent). A marker of the cellular response to low oxygen (HIF-1 alpha) roughly doubled during treatment and drifted back afterwards. The authors note these changes are much larger than the 2 to 5 per cent typically reported for diet and exercise interventions.

Why it might work

The proposed mechanism is the same hyperoxic-hypoxic paradox invoked in the group's other work: fluctuating oxygen during each session and between sessions mimics a shortage of oxygen at the cellular level, activating HIF-1 alpha and downstream pathways that can include telomerase activity and the clearance or reduced formation of senescent cells. Which of these actually accounts for the observed changes was not tested.

Limits

This is a small uncontrolled study with substantial sample loss for laboratory reasons, so results should be considered preliminary. Without a control group, measurement drift and seasonal or lifestyle changes cannot be excluded. Telomerase activity was not measured, and senescence was defined with one marker rather than a confirmatory pair. Effects were measured only weeks after treatment. Funding came from a neuroscience research network; three authors are employees and one a shareholder of a commercial hyperbaric company.

Paper 3

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

Hadanny et al. · BMC Geriatrics · 2024 · randomised controlled trial

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What they asked

Physical capacity declines with age alongside cognition, and the two are linked: the heart, blood vessels and mitochondria that supply working muscle also supply the brain. This trial from the same programme asked whether hyperbaric oxygen could improve maximal exercise capacity and blood flow to the heart muscle in sedentary but healthy older adults.

Who took part

Seventy adults over 64 enrolled and 63 completed (30 oxygen, 33 control). They were non-athletes living independently with good functional and cognitive status, and the exclusion criteria matched the cognitive trial: no recent cancer, no cognitive decline, no severe kidney disease, no uncontrolled diabetes, no smoking, no lung disease.

What they did

The oxygen group did 60 daily sessions over 12 weeks, five days a week, breathing 100 per cent oxygen at 2 ATA for 90 minutes with five-minute air breaks. The control group received no intervention. Both were asked to keep lifestyle and medication unchanged, and this was monitored. Before and more than a week after the course everyone did a maximal cycle test to measure oxygen uptake (VO2max), had cardiac MRI to measure blood flow and blood volume in the heart muscle, and had lung function tests. Assessors were blinded; participants were not.

What they found

VO2max per kilogram rose by about 1.9 ml/kg/min in the oxygen group relative to controls, a moderate effect, and oxygen uptake at the first ventilatory threshold (a marker of endurance) increased by around 160 ml/min. Cardiac MRI showed increased blood flow and blood volume in the heart muscle in the oxygen group with large effect sizes. Lung function did not change. Changes in myocardial blood volume correlated with changes in exercise capacity, which supports the idea that the improvement came from better perfusion rather than from lung mechanics.

Why it might work

The authors suggest that intermittent hyperoxia stimulates angiogenesis in the small vessels of the heart and improves mitochondrial function in muscle, both of which would raise the ceiling on oxygen delivery and use during exercise. They did not take muscle biopsies, so the mitochondrial part remains inferred.

Limits

No sham, participants unblinded, and 63 people is a modest sample. A daily three-month commitment to attending a hospital may itself change activity patterns despite monitoring. Testing was done more than a week after treatment, which argues against a purely transient effect, but long-term durability was not assessed. The optimal dose is unknown. Funding and conflicts were not clearly stated in the version we read; the senior authors have declared commercial interests in related papers.