Hyperbaric Oxygen Therapy Found to Improve Memory in Older People
Hyperbaric oxygen therapy (HBOT) — treatment in which patients are given pure oxygen — prevented the biological processes responsible for the development of Alzheimer’s disease in a mouse model, a study found.
Moreover, in a group of older people with memory loss, such oxygen therapy enhanced blood flow in the brain and improved overall cognitive abilities and memory, the study showed.
“By studying and treating Alzheimer’s disease in the animal model, we can implement our findings to include humans as well,” Uri Ashery, PhD, head of the Sagol School of Neuroscience at Tel Aviv University and a study co-author, said in a press release.
“After a series of hyperbaric treatments, elderly patients who were already suffering from memory loss showed an improvement of blood flow to the brain — as well as a real improvement in cognitive performance,” Ashery said. “Consequently, we succeeded in demonstrating the latent potential of hyperbaric medicine for treatment of neurologic conditions that originate from hypoxia — that is to say, a deficiency of oxygen reaching the cells.”
These findings suggest that “hyperbaric therapy given at a young age is likely to prevent this severe disease entirely,” said Ronit Shapira, PhD, a postdoctoral researcher at Tel Aviv University and the study’s lead author.
The study, “Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer’s disease mouse model and in elderly patients,” was published in the journal Aging.
Factors affecting the health of blood vessels, such as diabetes, obesity, smoking, and high blood pressure, increase the risk of Alzheimer’s disease and cognitive decline during aging.
The most common blood vessel-related (vascular) disease mechanism in Alzheimer’s is the buildup of amyloid plaques, which are hardened clumps of beta-amyloid proteins.
These plaques can reduce blood flow in the brain and lower oxygen levels — creating a condition called hypoxia — in patients, as well as precede the onset of dementia. They also correlate with the extent of cognitive impairment in individuals, according to the researchers.
Thus, treatments that improve blood vessel health may help enhance cognitive abilities in people experiencing declines in cognition due to Alzheimer’s or other related conditions.
Hyperbaric oxygen therapy or HBOT is the administration of 100% oxygen at a pressure greater than one atmosphere. It is approved in the U.S. for 13 indications — including decompression sickness resulting from scuba diving, for which it likely is best known — and has been used off-label to improve cognitive function following a stroke or a post-traumatic brain injury, known as a TBI.
Supported by clinical studies, hyperbaric oxygen therapy can help post-TBI patients by inducing the growth of new blood vessels in the brain, increasing brain (cerebral) blood flow and volume, and improving brain structure.
Now, investigators based at Tel Aviv University, in Israel, tested the impact of HBOT on an Alzheimer’s mouse model. Their goal was to uncover associated cellular and molecular mechanisms as well as evaluate the therapy in elderly people with significant memory loss.
“The combination of an animal model from which we could learn the pathology of the disease, together with existing and available therapy, raises the hope that we will now be able to fight one of the greatest challenges to the western world,” said Shapira. Of note, current estimates show the global prevalence of dementia may be as high as 24 million cases.
The 5XFAD mouse model, which rapidly develops severe amyloid plaque disease along with vascular abnormalities and cognitive impairment, was used in the study. Six-month-old 5XFAD and healthy mice were exposed to HBOT in a custom-made chamber at twice the atmospheric pressure for 60 minutes per day, five days a week, for four weeks — 20 hourlong treatments over one month).
After one month, an analysis of brain tissue found a significant reduction in amyloid plaques in the hippocampus, the brain area needed for learning and memory, which is especially vulnerable to damage at the early stages of Alzheimer’s.
To assess the impact of HBOT in vivo, or in a living organism, the team used two-photon microscope imaging that allows the imaging of living tissue. Here, HBOT was found to suppress the appearance of newly formed plaques and to reduce the volume of pre-existing plaques.
“Strikingly, HBOT halted the significant increase in volume of the small pre-existing plaques and facilitated reductions in the volumes of medium-sized and large plaques,” the team wrote.
To understand the molecular mechanisms that contributed to the reduction in amyloid plaques, the team conducted experiments to assess specific proteins involved in processing the amyloid precursor and clearance of amyloid protein. The results showed HBOT reduced enzymes involved in amyloid processing and increased the cellular activity of pathways associated with amyloid degradation and clearance.
From the beginning to the end of the study period, two-photon microscopy showed a significant reduction in blood vessel diameters over the month in control (not exposed to HBOT) 5XFAD mice. In contrast, in the treated mice, there was no decrease in blood vessel diameters following HBOT. The flow of red blood cells also significantly improved with HBOT when compared with controls (+82.82% vs. -20.35%), which directly showed that “HBOT alleviated reductions in blood vessel diameter, and, therefore, contributed to increased blood flow in 5XFAD mice,” the researchers wrote.
“This breakthrough was enabled thanks to a new research approach that employs multi-photon microscopes,” said Pablo Blinder, PhD, an assistant professor at the university and a study co-author.
‘This allowed us to follow up improvements in indices taken from animal models before and after each chamber treatment,” Blinder said. “At the same time, we check blood vessel diameters and the formation of amyloid plaques in their brains.”
In behavioral tasks, HBO-treated 5XFAD mice showed improved nest construction abilities and exploratory behavior than controls. Spatial recognition memory testing using a maze found control mice showed decreased time exploring new spaces over familiar ones. HBOT treatment significantly reversed this trend.
In a trace fear conditioning test, control mice demonstrated impaired contextual memory than normal littermates, as reflected by less freezing activity in the training chamber following conditioning. In comparison, this impairment was reversed in HBO-treated 5XFAD mice.
Finally, the team examined the ability of hyperbaric oxygen therapy to change brain blood flow and impact cognitive function in older adults. The human study (NCT02790541), called ANGIOHBOT, had enrolled 62 participants at Asaf Harofeh Medical Center, in Israel. The outcomes of six patients with significant memory loss, who had a mean age of 70, were reported in this study.
The participants’ mean overall cognitive score before HBOT was similar to the average score in the general population for the same age and education level, while memory scores were significantly lower. HBOT was conducted for 60 daily sessions at five sessions per week within three months. Each session included 100% oxygen at two atmospheres for 90 minutes with a five-minute air break every 20 minutes.
MRI scans showed hyperbaric oxygen therapy significantly increased blood flow in several brain areas from 16 to 23%, compared with before treatment. After HBOT, there was a significant increase in the overall cognitive score, from 102.4 to 109.5, in which memory, attention, and information processing speed scores were most improved. Furthermore, the post-HBOT mean memory scores improved from 86.6 to 100.9.
“The improvements in these scores correlate with improved short and working memory, and reduced times of calculation and response, as well as increased capacity to choose and concentrate on a relevant stimulus,” the researchers wrote.
The team said this is the first time that a non-drug therapy “has been proven effective in preventing the core biological processes responsible” for the development of Alzheimer’s disease.
Use of HBOT may be a new strategic approach for preventing Alzheimer’s, they said.
“By treating the root problem that causes cognitive deterioration with age, we are in fact mapping out the way to prevention,” said Shai Efrati, MD, a study co-author and an associate professor at both the Sackler School of Medicine and the Sagol School of Neuroscience at Tel Aviv University.
“It is likely that hyperbaric medicine can potentially provide the opportunity for living with good brain function without relating to chronological age,” Efrati said.
“The idea is to commence therapy before the onset of clinical symptoms of Dementia and before deterioration and loss of extensive brain tissue. This is the stage at which blood vessels become occluded, and the blood flow and the oxygen supply to the brain are diminished — a phenomenon that can already take place at a relatively early age,” he added.