Sydney: In a promising find to prevent dementia, scientists now report that reducing elevated pulse pressure in the blood can herald a new therapeutic target for preventing or slowing cognitive impairment.
Pulse pressure is the difference between systolic and diastolic blood pressure and commonly increases with age due to the stiffening of arteries and blood vessels. The normal range of pulse pressure is between 40 and 60 mm Hg.
In a paper published in the journal Frontiers in Neuroscience, researchers have outlined a pulse-pressure-induced pathway of cognitive decline that sheds light on why previous treatments for dementia may have failed.
"Over the last couple of 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," explained study co-author Mark Carnegie of The Brain Protection Company based in Australia.
Connecting a large and rapidly growing body of evidence, the researchers elucidate how elevated pulse pressure may cause dementia by disturbing the blood-brain barrier.
Elevated pulse 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.
There is significant evidence supporting that disruption of the blood-brain barrier is a key driver of cognitive decline and dementia.
Professor David Celermajer of The Brain Protection Company said that "this is an important paradigm shift in our understanding of the pathogenesis of dementia".
For the past two decades, a primary focus of drug development for Alzheimer's disease, the most prevalent form of dementia, has been to target the molecule amyloid-beta.
However, despite billions of dollars spent on R&D, that approach has yet to be successful.
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 the secretion of various inflammatory and oxidative molecules and amyloid-beta from the blood-brain barrier into brain tissue.
Stem and progenitor cell therapies have gained significant attention as potential strategies to repair blood-brain barrier damage and treat dementia, but chronic inflammatory and oxidative stress due to elevated pulse pressure can impact the health of stem and progenitor cells, said the researchers.
"The combination therapy has been paramount in the treatment of other challenging diseases, in particular cancer. Therefore, in dementia, reducing elevated pulse pressure could prove to be synergistic with other therapeutic approaches such as anti-amyloid-beta drugs or stem cell therapy," suggested Dr Rachel Levin, lead author of the paper.
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