Cranial Osteopathic Manipulative Medicine: A Therapeutic Modulator of Mechanisms in Aging and Alzheimer's Disease

Abstract

In the United States, the number of citizens 65 and older is projected to increase from 58 million in 2022 to 82 million by 2050, driven by the second largest generation, Baby Boomers. The national rise in this demographic corresponds with an expected increase in individuals diagnosed with age related symptoms and diseases such as Alzheimer's Disease (AD). AD is a progressive neurodegenerative disease that affects over 7 million individuals in the US. Though no single cause of AD has been identified, age related declines in cerebral waste clearance is considered a contributor. The meningeal lymphatic and glymphatic systems in the brain ensure proper fluid circulation for sufficient glucose uptake and removal of waste products like amyloid-beta (Aβ). When these systems are impaired, waste builds-up and fluid flow is reduced, leading to the development of neuroinflammation and a decline in glucose uptake. Neuronal cell dysfunction and death arises, which causes cognitive decline and progressively dementia. Since both aging and AD are associated with poor clearance, the meningeal and glymphatic systems are promising targets for treatment. However, there are currently no Federal Drug Administration (FDA) -approved therapies designed to directly restore proper cerebral fluid circulation. This highlights the need for a readily available treatment, especially when considering the lengthy drug development and approval process. To address this need, this research aimed to investigate the effects of Cranial Osteopathic Manipulation (COM) via compression of the fourth ventricle (CV4) as a treatment for the behavioral and molecular effects associated with aging and AD. COM, via CV4, is a gentle force-based technique that appears as a massage to the back of the head. The intended effects are to stimulate self-healing within the body by improving cranial rhythmic impulse and potentially cerebral fluid circulation. Literature supports this concept as evidence has shown increased expression of proteins involved in fluid clearance and enhanced interstitial fluid flow after treatment. However, a comprehensive evaluation on effects of treatment have yet to be established. Therefore, this work investigated the effects of COM behaviorally and molecularly in 18-month-old rodent wild-type (Wt) and transgenic (Tg) rat models of aging and AD, respectively. Findings demonstrated that COM is a promising preventative or mitigative treatment option to be used at earlier stages of decline in memory. When exploring sex specific effects, females had a positive response to treatment, while males had a less favorable response. This work provides a foundational framework for future studies aimed at defining treatment paradigms, elucidating sex-specific responses, and advancing toward translational and clinical evaluation.