Reducing Elevated Pulse Pressure Could Improve Dementia Treatment

According to a new study, elevated pulse pressure can contribute to the development of dementia as well as the reduced efficacy of some dementia therapeutics.  

"Over the last couple years, a sea change in dementia and Alzheimer's disease research has occurred. Focus has shifted from solely targeting amyloid-beta in the brain to the opinion that more fruitful progress could be made by addressing factors that compromise the blood brain barrier," explains Mark Carnegie, co-author of a paper published in Frontiers in Neuroscience today. "Elements of the constellation include chronic age-related inflammation, genetic predisposition, and cardiovascular abnormalities, notably high blood pulse pressure."

The researchers propose that elevated pulse pressure, which is the difference between systolic and diastolic blood pressure, in blood travelling to the brain can cause inflammation, oxidative stress, mechanical stress, cellular dysfunction, and cell death in the blood brain barrier that leads to brain damage.

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

Senior author of the paper, Prof. David Celermajer of The Brain Protection Company, explains that "although there are likely several causes of blood brain barrier disruption, recent human cell culture experiments, animal models, and epidemiological evidence have pointed to high blood pulse pressure as one potential key cause."

The authors also discuss how elevated pulse pressure may have also prevented previous treatment strategies from working optimally against dementia. For the past two decades, a primary focus of drug development for Alzheimer's disease has been to target amyloid-beta. The researchers suggest that targeting amyloid-beta alone to treat dementia may be an uphill battle since concurrent elevated pulse pressure will continue to activate secretion of various inflammatory and oxidative molecules and amyloid-beta from the blood brain barrier into brain tissue.