Could brain pulsatility be key in dementia prevention?

Sergio Dempsey stands in front of a room full of academics and challenges them to hold their breath for as long as they can. Most give up pretty soon, but some stalwarts last more than two minutes.

If the ‘winners’ feel smug, it’s not for long, because now Dempsey tells them the impact this simple exercise may have on their brains.

Holding one’s breath impacts something he calls brain “pulsatility transmission”– in other words, how the throb or pressure wave of the blood changes when flowing through the large arteries and into smaller blood vessels and capillaries in the brain.

Based on each person's unique physiology, transmission may increase or decrease. And while an increase sounds like a good thing, actually it isn’t; certainly not long term.

Damage is not going to happen from one exercise in a University of Auckland lecture theatre, Dempsey says. But over months or years, researchers believe an overly strong pulsatility – often observed during stress and also linked with high blood pressure (not just from holding your breath!) – could signal problems to come. 

Research suggests strong pulsatility might precede the formation of amyloid proteins in the brain, which are commonly the first risk signs of Alzheimer’s disease, Dempsey says. 

Pulsatility problems might even initiate dementia symptoms over decades of exposure.

Currently, in New Zealand, 70,000 people live with dementia, and this figure could reach 250,000 by 2050. The World Health Organization estimates more than 55 million people have dementia worldwide and nearly 10 million more are diagnosed every year.

Dempsey’s PhD focused on dementia risk. The first step involved collaborative research involving the Auckland Bioengineering Institute and Mātai, a Gisborne-based medical research institute, to develop the transmission index.

Using 4D flow MRI – an advanced scanning technology – the team has been able to accurately measure the pulse wave change through the brain vessels.

Now Dempsey and a team led by Dr Gonzalo Maso Talou, a senior research fellow at the Auckland Bioengineering institute (ABI) and leader of its Animus Laboratory, have pushed the research a step further.

They’ve taken 10 healthy participants, given them carbon dioxide, and measured whether that changed the way the blood pulse transmitted through the small blood vessels in the brain. 

And they found it did.

“This second study suggests there is something we can do – that pulsatility transmission is changeable, and perhaps something we can change.” 

The argument is if doctors could look at the brain of someone in their 30s or 40s, and if they found that person had a problem with high pulsatility and could then correct it, that could potentially stave off dementia later on. 

“That 20- to 30-year head start is phenomenal because dementia risk is not fixed. Early lifestyle changes or clinical treatments may delay the development of the disease,” Dempsey says.

“At the moment, there is no screening for dementia at 30 or 40 years old. In other parts of the world, amyloid and tau proteins are the main means of exploring the early onset of neurodegeneration related to dementia. A PET scan might show elevated amyloid protein in the brain, but this is not likely to occur before a person has reached 60 years of age.“

These are all ‘late signs’, and they will stay late. Our work at ABI looks at the science that precedes amyloid formation.”

One particularly exciting finding, Dempsey says, is that the carbon dioxide study suggests women are more likely to have problems regulating high pulsatility transmission after inhaling the gas than men, which could be one reason for the higher rate of dementia in women.

Almost twice as many women have Alzheimer’s disease – the most common form of dementia – compared to men, according to figures from the Alzheimer Society in the UK, though that figure also reflects the fact women live longer.

In the not-too-distant future, Dempsey can see standard MRI sequences converted into clinical reports for radiologists and doctors and New Zealand leading the way in preventative dementia risk assessment. 

“We now need funding for a larger study of one hundred people to firmly establish our observations and test lifestyle interventions, perhaps with exercise, stress reduction or better sleep.” 

Dr Gonzalo Maso Talou, who was also Dempsey’s supervisor for his newly-completed PhD research, says the next stage is critical.

“This larger study will provide novel, world-leading diagnostic techniques to explore one of the most terrible conditions affecting many families in New Zealand. Blood flow in the brain is a strong candidate to characterize early damage caused by dementia diseases. 

“Now, we want to go one step further to investigate how we can diagnose early in life and give a better fighting chance to those affected by dementia.”

ABI director Professor Merryn Tawhai says the project is a good example of the Institute's researchers thinking outside the box.

“One of our main goals is to improve medical diagnosis and treatment of disease, and sometimes you have to approach the problem from a fresh angle. 

"The research Sergio and the team are doing pushes the boundaries and could help improve the lives of tens of millions of people each year.”