Hyperbaric oxygen therapy as new treatment approach for Alzheimer’s Disease
Hyperbaric oxygen therapy as a new treatment approach for Alzheimer’s disease (AD): Alongside the increase in life expectancy, the prevalence of age-related disorders, such as neurodegenerative diseases, is on the rise. For example, AD, the most common form of dementia in the elderly, accounts for 60–80% of all dementia cases. However, there is presently no cure for this disease and no effective treatment that would slow disease progression despite billions of dollars invested in drug development. As AD is a complex disease, the development of effective and specific drugs is difficult. Thus, examining alternative treatments that target several disease-related pathways in parallel is of the utmost importance. Hyperbaric oxygen treatment (HBOT) is the medical administration of 100% oxygen at environmental pressure greater than 1 atmosphere absolute (ATA). HBOT has been shown to improve neurological functions and life quality following neurological incidents such as stroke and traumatic brain injury, and to improve performance of healthy subjects in multitasking. The current perspective describes a recent study demonstrating that HBOT can ameliorate AD-related pathologies in an AD mouse model, and provides unique insights into HBOT’s mechanisms of action. Old triple-transgenic model (3xTg)-AD mice were exposed to 14 days of HBOT and showed reduced hypoxia and neuroinflammation, reduction in beta-amyloid (Aβ) plaques and phosphorylated tau, and improvement in behavioral tasks. This and additional studies have shown that cerebral ischemia is a common denominator in many of the pathological pathways and suggests that oxygen is an important tool in the arsenal for our fight against AD. Given that HBOT is used in the clinic to treat various neurological conditions, we suggest that this approach presents a new platform for the treatment of AD.
Dementia and AD: Dementia, a disorder characterized by chronic deterioration of cognitive function, affects 47.5 million people worldwide. AD is the most common form of dementia in the elderly, accounting for most of the cases. Although several drugs have been approved for AD patients, they have limited effects on disease progression and fail in the recovery of cognitive capacity once the disease has progressed. Therefore, there is a real need for new and early interventions.
Implications for treatment of AD patients: The growing understanding of the importance of oxygen in brain functionality under normal and diseased conditions marks it as a key player in AD treatment. As such, HBOT emerges as a well-tolerated, safe and effective platform to enhance brain oxygenation. Due to its neuroprotective effects, HBOT is used to treat various neurological conditions associated with hypoxia (such as stroke, ischemia and traumatic brain injury). Our recent findings lay the first stone for the use of HBOT in the treatment of AD as well. Unfortunately, when AD is clinically diagnosed, the patients already have significant brain atrophy, which means significant tissue loss that cannot be recovered. Moreover, AD patients present different pathological patterns and severities, making them a heterogeneous population. Therefore, one of the most important challenges in the application of HBOT to the clinical setting is to identify the subpopulation of patients which will benefit the most from the treatment. The classical candidate for HBOT would be a patient in the early stages of AD, before it is fully developed. Hence, early biomarkers for AD should be sought (blood, cerebral spinal fluid, imaging, and cognitive indications) and measured routinely. When deterioration in these measures is detected before significant functional decline, HBOT should be applied. Early diagnosis of AD will enable treatment when irreversible damage is still minimal, thereby maximizing the effect of HBOT.
In summary, we discussed the effects of HBOT on the pathology of the 3xTg mouse model of AD. Application of HBOT in the clinic calls for further optimization to achieve similar effects in human patients. Specifically, the optimal or ideal treatment should be determined with respect to oxygen pressure, time of treatment, and sustainability of the treatment. We expect that similar to other neurological disorders, HBOT will show promising results in the treatment of AD.