A game changer in the fight against dementia

A recent article published in Frontiers in neuroscience, describes a pathway of cognitive decline induced by pulse pressure that sheds light on why previous treatments for dementia may have failed and proposes promising new directions for the prevention and treatment of dementia.

“In the past two years, there has been a sea change in dementia and Alzheimer’s disease research. The focus has shifted from focusing solely on beta amyloid in the brain to the belief that further progress could be made. fruitful in addressing the factors that compromise the blood-brain barrier, “explains co-author Mark Carnegie of The Brain Protection Company based in Australia. “Elements of the constellation include chronic age-related inflammation, genetic predisposition, and cardiovascular abnormalities, especially high blood pressure.”

Connecting a large and rapidly growing body of evidence, the researchers elucidate how elevated pulse pressure can cause dementia. Pulse pressure is the difference between systolic and diastolic blood pressure and commonly increases with age.

The researchers propose that elevated pulse pressure in the blood traveling to the brain can cause inflammation, oxidative stress, mechanical stress, cell dysfunction, and cell death in the blood-brain barrier that leads to brain damage.

The link between collapse of the blood-brain barrier and dementia is intuitive, as the blood-brain barrier has evolved specifically to support and protect delicate brain tissue by preventing circulating cells, pathogens, and other unhealthy substances in the blood from infiltrating in the brain. There is significant evidence to support that disruption of the blood-brain barrier is a key factor in cognitive decline and dementia.

The paper’s lead author, Professor David Celermajer of The Brain Protection Company, says, “This is a major paradigm shift in our understanding of the pathogenesis of dementia.”

In addition, he adds that “although there are likely several causes of disruption of the blood-brain barrier, recent human cell culture experiments, animal models, and epidemiological evidence have indicated that high blood pressure is a possible key cause.”

Thus, pulse pressure may be a promising new therapeutic target to prevent or slow cognitive decline, bringing new hope in the fight against dementia.

Furthermore, the authors discuss how elevated pulse pressure may also have prevented previous treatment strategies from working optimally against dementia.

For the past two decades, a primary focus of drug development for Alzheimer’s disease, the most common form of dementia, has been to attack the beta amyloid molecule. However, despite the billions of dollars spent on R&D, that approach has yet to succeed.

The researchers suggest that targeting beta amyloid alone to treat dementia can be an uphill battle as concurrent elevated pulse pressure will continue to activate the secretion of various inflammatory and oxidative molecules and beta amyloid from the blood-brain barrier to brain tissue.

In addition, stem and progenitor cell therapies have received significant attention as potential strategies to repair damage to the blood-brain barrier and treat dementia, but chronic inflammatory and oxidative stress due to elevated pulse pressure can affect the health of women. stem and progenitor cells.

Dr. Rachel Levin, lead author of the article, says that “combination therapy has been paramount in treating other challenging diseases, particularly cancer. Therefore, in dementia, lowering high pulse pressure may be synergistic with other therapeutic approaches such as anti-amyloid beta drugs or stem cell therapy. “

The authors issue a call to action for academic and industry leaders to develop new candidate drugs or devices that reduce elevated pulse pressure and progress them to clinical trials. Celermajer asserts that “solid animal model data already supports the role of high pulse pressure in altering the blood-brain barrier and the pathology of dementia; more human studies are now needed.”