Mental abilities change throughout life, first as a result of brain maturation and later with the ageing of brain cells and their billions of complex interconnections. As we age, our cognitive abilities like conceptual reasoning, processing speed, problem-solving activities decline gradually over time. Multi-tasking and dividing attention effectively to each task seems nearly impossible.
Aging produces microscale cellular and subcellular level changes that affect neural network and synaptic plasticity. Besides structural changes, cerebrovascular dysfunction is an additional distinctive feature of ageing that includes regional decreases in cerebral blood flow (CBF), and a decrease in brain metabolism. Research shows that with time, altered brain metabolism contributes to a general decline in cognitive functions. Whilst shocking, the complex interplay between metabolism and brain function has been known for years. What remains unclear is whether restoring normal brain metabolism could help halt or delay age-related cognitive decline.
This idea was recently put to test by Professor Shai Efrati and colleagues at the Sagol Centre for Hyperbaric Medicine and Research in Tel Aviv- where they investigated the effects of hyperbaric oxygen therapy (HBOT) as treatment for age-related cognitive decline in healthy older adults. Their theory was that cognitive ageing could be halted by refuelling the brain – re-establishing the vascular supply in various brain regions. Their study showed that HBOT treatment – which consisted in applying 100% pure oxygen to 65-plus patients in pressurised environments (i.e. a hyperbaric chamber) five times a week – can help improve cognitive functions. How? Researchers claim that HBOT increases oxygen solubility in the blood inducing cellular mechanisms needed for regeneration of blood cells. In other words, this treatment may stimulate the release of growth factors and stem cells, and in-turn, trigger the physiological regeneration of blood vessels – ultimately increasing the brain’s blood flow.
Researchers claim that HBOT increases oxygen solubility in the blood inducing cellular mechanisms needed for regeneration of blood cells
I had the pleasure of speaking with Dr. Amir Hadanny, one of the contributing authors of this research. He is a neurosurgeon, and a hyperbaric physician. He has published more than 25 research papers focused on the effects of HBOT and its impact on cognitive and physical performance. His previous collaborations with the Sagol Center focused on the HBOT protocols to restore brain function in post-stroke patients in the chronic stage of recovery, as well as in traumatic brain injury patients. In the near future, the team aims to examine the potential of HBOT in treating other cognitive conditions such as PTSD, claiming that emotional trauma has a biological impact on the brain. Below, you can read our full interview with Dr. Amir Hadanny
1. What is the main finding of your study? Could you give an overview of your investigation and its impact on future neuroscience research?
The study demonstrated for the first time in humans that specifically designed hyperbaric oxygen therapy (HBOT) protocols can significantly enhance the cognitive performance of healthy older adults. Prof. Shai Efrati and I designed our study based on unique HBOT protocols, which we developed at the Sagol Center over the past 10 years. The randomized controlled clinical trial included 63 healthy adults (>64) who underwent either HBOT(n=29) or a control period (n=33) (natural aging over time with no active treatment) for three months. The study’s primary endpoint included a change in the general cognitive function, which we measured using a comprehensive battery of computerized, standardized cognitive assessments before and after the intervention or control. We evaluated cerebral blood flow (CBF) using a novel magnetic resonance imaging technique for brain perfusion. This landmark research can impact the way we view and treat the aging process.
2. What is Hyperbaric Oxygen Therapy (HBOT)? Could you tell us a bit more about its application in clinical medicine?
Hyperbaric oxygen therapy (HBOT) utilizes 100 percent oxygen in an environmental pressure higher than one absolute atmosphere (ATA). This enhances the amount of oxygen dissolved in the body’s tissues which initiates a cascade of regenerative metabolic events including angiogenesis -the creation of new blood vessels. HBOT has historically been used to encourage the healing of carbon monoxide poisoning, diving accidents, severe infections, diabetic non-healing wounds, radiation injuries among many other conditions, and has proven safe and effective. By increasing blood oxygenation, we can trigger the regeneration processes which includes the creation of new blood vessels to help the body heal itself.
Outside view of the HBOT chambers where patients received the oxygen treatment at the Sagol Centre for Hyperbaric Oxygen Therapy in Tel Aviv, Israel. Credit: Sagol Centre for Hyperbaric Oxygen Therapy.
3. The brain shrinks with increasing age and there are changes at all levels from molecules to morphology. What is the consequence of age-related changes in Memory and Cognition?
Age-related cognitive decline is characterized as a gradual decline in cognitive capacity in the normal aging process. Some cognitive abilities -such as processing speed, attention, conceptual reasoning, and memory -decline and slow gradually over time due to structural brain changes. Gray and Areas of the central nervous system that consist primarily o... volume in the brain begin to decrease as we age, which may be due to the death of neurons or by the decrease in neuronal size and synaptic density. Neurons undergo morphologic changes with aging including decreased Process that arises from a neuron and receives input from ot... length among other changes. These morphologic changes likely contribute directly to the reduction of synaptic density, leading to cognitive decline as people age.
Some cognitive abilities -such as processing speed, attention, conceptual reasoning, and memory –decline and slow gradually over time due to structural brain changes.
4. Describe the Hyperbaric Oxygen Therapy (HBOT) protocol and the mechanism of how the Hyperoxic-Hypoxic Paradox can restore brain function.
The protocol included 60 sessions of 100 percent oxygen at 2 ATA including 3 air breaks during each session. By applying 100 percent oxygen in such intervals, we make use of what we named the Hyperoxic-Hypoxic Paradox. Repeated intermittent hyperoxia (increased oxygen levels) can induce many mediators and cellular mechanisms that are usually induced during hypoxia (decreased oxygen levels). The Hyperoxic-Hypoxic Paradox, in essence, “tricks” the body into a state of hypoxia through these intervals, triggering regenerative mechanisms, including stem cell proliferation and angiogenesis. Angiogenesis is induced mainly in brain regions signaling ischemia (decreased blood supply) or metabolic dysfunction. In turn, the formation of new blood vessels can enhance cerebral blood flow and consequently improve the neuronal metabolic activity.
Inside view of the HBOT chambers where patients received the treatment at the Sagol Centre for Hyperbaric Oxygen Therapy in Tel Aviv, Israel. Credit: Sagol Centre for Hyperbaric Oxygen Therapy.
5. Nootropics“smart drugs” are already proven to have a therapeutic role in the treatment of cognitive deficits. What is the added significance of HyperbaricOxygen Therapy? On comparing both interventions, which one provides long term benefits?
Some nootropics, particularly stimulants such as Ritalin or Adderall, have been extensively researched and used widely in patients with ADHD for significant positive results in brain function. There is a second group of synthetic compounds that affect the key neurotransmitters The principal excitatory neurotransmitter in the nervous sys... and acetylcholine, which have become known to provide mild memory enhancements in people with brain injuries or pathological cognitive decline but have no demonstrable effect on healthy individuals. What is most exciting about our research is that the present study shows a positive effect of HBOT on “normal” healthy aging adults – meaning, one does not have to endure a brain injury to derive benefit from this treatment. Repeated HBOT treatment can improve global cognitive scores, memory, attention, and other cognitive metrics in healthy aging adults – this is what we have demonstrated for the first time.
6. What was the biggest challenge in your discovery?
The current study has several limitations to consider. First, the limited sample size must be noted, possibly contributing to decreased sensitivity and false negative changes. Second, the control group was non-intervention rather than a sham-intervention. Although the outcome assessors were blinded, the participants were unblinded. Third, the duration of the effect is yet to be determined in long-term follow-ups. We are continuing our research to determine the longer-term effects, and to develop a testing methodology that may allow for a reasonable double-blind study, which has always been a challenge with research in hyperbaric medicine.
7. The study was conducted on healthy aging adults. Do you think its findings could be expanded to patients suffering from chronic neurological diseases such as Alzheimer’s? Would you expect improvements in cognitive performance in AD patients or has any study looked at this?
We believe that our study has implications that reach beyond the healthy aging population. Our vision is to enable a generation of older adults that is Alzheimer’s free. The hypothesis is if we can introduce this treatment earlier in healthy adults, we may potentially prevent the onset of Alzheimer’s altogether. We are far too early in our research to prove this hypothesis right now – but that is the vision. We are, however, performing studies in mice models currently in collaboration with The Sagol School of Neuroscience at Tel Aviv University. The goal of this collaboration is to understand the biological effects of HBOT at the basic molecular level in order to slow down or prevent Alzheimer’s.
Interested in what neuroscientists are doing to slow cognitive decline? Perhaps changing your diet is all what it takes to ensure healthy ageing!
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— Written by Charmi Porwal. Illustrated by Gil Torten..
— This article was edited by Marco Travaglio and Nerissa Culi.