Billions of dollars and decades devoted to drug development for Alzheimer's disease and other dementias haven't led us to a cure or effective single-targeted treatment for these progressive diseases. The difficulties in treatment development lie in the complexity of the disease and the multiple underlying root causes, factors, and pathways involved in neurodegeneration and cognitive decline. However, there may be applicable uses of existing novel protocols, specifically hyperbaric oxygen therapy (HBOT), which in some instances could effectively slow disease progression.
What We Know
Alzheimer's disease (AD) is a progressive, chronic illness that degenerates the brain and progresses at varying rates into advanced stages of dementia. In its most advanced stages, AD is distinguishable from other types of dementia. There is considerable debate as to what underlying factors and root causes may initiate this illness. Additionally, there are many factors such as underlying infections, toxins and multiple environmental and inflammatory factors that affect the degree of decline and manifestation of symptoms. The more challenging questions with which scientists and clinicians struggle is identifying biomarkers that can differentiate between AD and non-AD dementia pathology at their preclinical stages.
Numerous studies highlight amyloid accumulation as a possible early marker for AD1 and data suggest that the amount and distribution of tau proteins 2 provide substantial evidence distinguishing AD progression. Now, both amyloid and tau protein positron emission tomography (PET) imaging are available. Often, accumulation of these biomarkers is seen before any behavioral or cognitive symptoms of dementia develop. Amyloid & tau identification have not led to the development of any viable treatment approaches, however. There is controversy, in fact, as to whether the “amyloid hypothesis” is even important, and current thinking in the functional medicine communities is that amyloid actually builds up as a “protective” protein against underling inflammation & immune responses. Dale Bredesen, MD, in his book The End of Alzheimer’s, as well as other authors have identified root causes which may instigate amyloid build-up.
Biomarkers and their role in understanding AD
Researchers have sought other biomarkers that emerge at the preclinical stages of AD in the hopes of finding possible treatment in both symptomatic relief and suggestions for prevention. It is known that both vascular pathology and glial cell degeneration play a role in various types of dementias due to the declination of oxygenated blood transfer to the neurons. Without sufficient oxygen supply, the neurons cannot function well and subsequently are prone to degenerate. Vascular pathology on larger scales can cause noticeable disruptions in specific areas, and usually disrupt functions like memory loss, language problems, etc. A stroke or traumatic brain injury can cause these larger-scale disruptions. However, injuries contain the damages to a specific area, and the symptoms may subside over time.3 When talking about biomarkers for Alzheimer's disease, cerebrovascular pathologies are usually much smaller- scaled, spreading microscopic lesions on the vessels that continuously disrupt the brain's normal blood flow and oxygenation.
However, identifying preclinical markers and biomarkers is of limited value because the disease is typically far too advanced once amyloid and tau have accumulated. Recent studies suggest informative clinical implications of white matter hyperintensities in older adults' MRI scans. The white matter hyperintensities are typically interpreted as surrogates of cerebral small vessel disease (CSVD). Microinfarcts, microbleeds, and brain atrophy also count as contributing factors to CSVD. 5 A recent systematic review suggests that white matter hyperintensities contribute to information-processing speed and executive function declinations.6 Longitudinal evidence points to cognitive decline predictions and mild cognitive impairment with consistent increases of white matter hyperintensity volumes.
White matter hyperintensity plays a crucial role in identifying presence of neurodegenerative lesions. In general, to avoid cerebrovascular pathology including white matter hyperintensities, we know that maintaining healthy blood pressure levels in mid to older adulthood can be preventative in the development of CSVD. Higher body fat, low levels of B12, smoking, and high levels of blood-based inflammatory markers are all risk factors for developing the disease.
Could oxygen be a vital element in the treatment of neurological disorders?
There are novel multifactorial approaches that take into account the numerous root causes that can contribute to neurodegeneration. Oxygen availability, or lack thereof, in the brain is one of these causes. As such, there is increasing evidence for a strong relationship between oxygen bioavailability and brain functionality as they relate to neurological deficits. 4 Studies have shown that hyperbaric oxygen therapy may improve Alzheimer's disease pathology and cognitive deficits. This new treatment involves the medical administration of pure oxygen in a pressurized room or chamber. Patients undergoing this treatment inhale 100% oxygen at environmental pressure greater than 1 Absolute Atmosphere (ATA). Repeated hyperbaric oxygen therapy (HBOT) sessions can drive up oxygen solubility in the blood, which stimulates the production of healing growth factors and stem cells throughout the body and brain.
In studies using animal models, subjects with Alzheimer’s were exposed to hyperbaric oxygen therapy for 60 minutes/day over 14 days showed attenuated neuroinflammation, reduced amyloid burden, and decreased tau phosphorylation. In one patient with rapidly progressing Alzheimer's, PET imaging revealed increased metabolism in the brain's typical AD diagnostic areas after 8 weeks of hyperbaric oxygen therapy. Though it isn't exactly clear the mechanism of action, researchers believe that increased oxygen exposure can promote tissue healing, relieve swelling and inflammation in the brain, reduce apoptosis, increase mitochondrial function, and promote cell differentiation and regeneration. 9
Recently, researchers reported that a consistent 20-day hyperbaric oxygen treatment (HBOT) improved Alzheimer's patients' cognitive function at a one-month follow up and for mildly cognitively impaired patients at a three months. They also found that the treatment reduced brain glucose metabolism in both patient groups, suggesting less energy was needed and less time was spent on simple and cognitively taxing tasks.10 Knowing the effectiveness of hyperbaric oxygen treatment on stroke and traumatic brain injury patients, it is understood that increasing the brain's oxygen levels can heal damaged neural tissue and enhance cognitive function. HBOT, when given repeatedly can have regenerative effects after hypoxic events.
We only have seen a limited number of human studies regarding this treatment and healing cognitive impairment. While initial results seem to indicate a decline in the progression of AD in early stages, it’s possible that the treatment may not be as effective when the patient is in more advanced stages of the disease.11
As far as other conditions, there are several instances the treatment has been shown to have remedial value. Researchers noted HBOT’s promising effects in the management of fibromyalgia and other chronic pain disorders where its anti-inflammatory properties were most impactful. Still even more studies have indicated its effectiveness as a potential stroke therapeutic, reporting reductions in oxidative stress, inflammation, and neural apoptosis.
It’s important to acknowledge the speculation that if an infection or toxic burden like mold is the underlying root cause, then HBOT may not be at all beneficial and could in fact temporarily make things worse. But in light of some of the research findings, it’s equally important to keep an open mind while supporting the study of novel strategies as potential treatments in neurodegenerative illnesses.
The brain, anti-aging and HBOT
Based upon current data, it’s quite possible that hyperbaric oxygen therapy may be the “next big thing” in anti-aging efforts in healthy adults, at least when it comes to our brains. In a recent study, thirty-five individuals age 64 and older were given a series of 60 HBOT sessions over a period of 90 days. The researchers obtained blood samples from the subjects before and after treatment and found that after the 30th and 60th sessions, the length of telomeres had increased and there was a clearing of senescence cells.
Another investigation examined HBOT’s effects on cognitive enhancement in healthy aging adults, using magnetic resonance imaging (MRI) to evaluate cerebral blood flow. Primary findings post-HBOT administration included improvements in attention, information processing speed and executive functions, all of which normally decline with aging.
As we explore the full range of this novel treatment for various neurological diseases, researchers continue to stress the importance of initiating this protocol in the early stages of a disorder and before significant degeneration has occurred. While HBOT’s potential does seem highly promising, we also recognize the need to continue to exercise caution in its application and that no single targeted strategy can remedy all of the complex underlying causes in the spectrum of neurological illness.
References:
1 Murphy, M. P., & LeVine, H., 3rd (2010). Alzheimer's disease and the amyloid-beta peptide. Journal of Alzheimer's disease: JAD, 19(1), 311–323. https://doi.org/10.3233/JAD-2010-1221.
2 Braak, H., & Del Tredici, K. (2018). Spreading of Tau Pathology in Sporadic Alzheimer's Disease Along Cortico-cortical Top-Down Connections. Cerebral cortex (New York, N.Y. : 1991), 28(9), 3372–3384. https://doi.org/10.1093/cercor/bhy152
3 Miyakawa T. Vascular pathology in Alzheimer's disease. Psychogeriatrics. 2010 Mar;10(1):39-44. doi: 10.1111/j.1479-8301.2009.00294.x. PMID: 20608291.
4 Brickman, A. M., Tosto, G., Gutierrez, J., Andrews, H., Gu, Y., Narkhede, A., Rizvi, B., Guzman, V., Manly, J. J., Vonsattel, J. P., Schupf, N., Mayeux, R. An MRI measure of degenerative and cerebrovascular pathology in Alzheimer disease. Neurology. 2018, 91 (15) e1402-e1412; DOI: 10.1212/WNL.0000000000006310
5 Li, Q., Yang, Y., Reis, C., Tao, T., Li, W., Li, X., & Zhang, J. H. (2018). Cerebral Small Vessel Disease. Cell transplantation, 27(12), 1711–1722. https://doi.org/10.1177/0963689718795148.
6 R.P. Kloppenborg, P.J. Nederkoorn, M.I. Geerlings, E. van den Berg. Presence and progression of white matter hyperintensities and cognition: a meta-analysis. Neurology, 82 (2014), pp. 2127-2138.
7 N.D. Prins, P. Scheltens. White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol, 11 (2015).
8 Alber, J., Alladi, S., Bae, H., Barton, D., et al. White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities, 2019. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 5, 107-117.
9 Harch, P. G., & Fogarty, E. F. (2019). Hyperbaric oxygen therapy for Alzheimer's dementia with positron emission tomography imaging: a case report. Medical gas research, 8(4), 181–184. https://doi.org/10.4103/2045-9912.248271.
10 Chen, J., Zhang, F., Zhao, L., Cheng, C., Zhoung, R., Dong, C., Weidong, L. 2020. Hyperbaric oxygen ameliorates cognitive impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment. Alzheimer’s & Dementia: Translational Research & Clinical Intervention, 6(1). https://doi.org/10.1002/trc2.12030
11 Shapira, R., Efrati, S., & Ashery, U. (2018). Hyperbaric oxygen therapy as a new treatment approach for Alzheimer's disease. Neural regeneration research, 13(5), 817–818. https://doi.org/10.4103/1673-5374.232475
Hachmo, Y., Hadanny, A., Hamed, R.A., Daniel-Kotovsky, M., Catalogna, M., Fishlev, G., Lang, E., Polak, N., Doenyas, K., Friedman, M., Zemel, Y., Bechor, Y, Efrati, S
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