Professor Pat Kehoe is the chief investigator on a new ground-breaking clinical trial (RADAR) on Join Dementia Research, which is examining how a commonly used blood pressure drug called losartan could slow down the rate of progression in Alzheimer’s disease. The study is funded by an MRC and NIHR partnership.

Pat heads the Dementia Research Group at the University of Bristol, and has been working in the dementia field for almost 20 years.

How did you become involved in working in the field of dementia?

It was actually during my PhD, where I was researching the genetics of Alzheimer’s disease. It was an exciting time as the first familial genes for Alzheimer’s disease genes were being identified. However, with no treatments or cure, I felt there was a long fight to be had and I definitely liked the idea of the challenge.

In fact, some of the scientific background to the RADAR study actually started in a laboratory for me, so I have been really fortunate enough to progress those first discoveries right through to a clinical trial.

What motivates you about working in this field?

Six months after starting work in the field of dementia, one of my grandparents had a stroke and sadly went on to develop dementia. Another one of my grandparents developed Alzheimer’s about 10 years later. So I do have a interest due to both my family as well as a societal motivation.

Dementia affects a huge number of people, nearly 1 million people in the UK by current estimates, and has a huge impact on their families as well; and we all need to do something about it.

Could you give some background to the RADAR study? How did it come about? What does RADAR stand for?

Over the last two decades, a number of studies have shown that people who have high blood pressure in middle age are at increased risk of developing dementia in later life. The assumption has been that keeping blood pressure down can reduce peoples’ risk of stroke and therefore reduce dementia.

In other words, there is a strong vascular element (i.e affecting the blood vessels) as people age, blood vessels in the brain and body don’t always work so well.

However, other studies have also shown that a common gene involved in high blood pressure regulation is also associated with an increased risk of Alzheimer’s disease.

RADAR actually stands for ‘Reducing pathology in Alzheimer’s Disease through Angiotensin taRgeting’.

There is evidence that the malfunction of this a hormonal system that regulates blood pressure (renin–angiotensin) also contributes to some of the biochemical processes that go on to cause the damage to the brain that appears in Alzheimer’s disease.

The RADAR study will test whether losartan, that stops the activity of a central component in the renin angiotensin hormone system, will reduce rates of brain shrinkage, vascular damage and cognitive impairment that are all common features in Alzheimer’s disease.

Why losaratan, rather than another blood pressure drug?

We know from studies that people who have previously taken losartan and similar drugs, have a lower risk of developing Alzheimer’s disease compared to other blood pressure drugs.

It is thought that losartan might also have additional benefits in reducing inflammation in the brain, reducing the release of other damaging chemicals that occur when the brain is taking damage from disease, and improving blood flow around the brain.

Losartan is also already commonly available, and we already know a lot about it’s safety record and how it affects people.

Therefore using losartan offers many advantages than say a new drug that has only recently been made in a laboratory and has only been tested recently in people for its safety.

We are hoping that it will slow down the rate that Alzheimer’s disease progresses and ultimately benefit the way peoples’ cognitive performance will last.

What impact would this delay have for people and society?

If we can delay the onset of Alzheimer disease by five years, we can half the number of people affected at any one time. There would be a substantial social and economic saving to the UK, not to mention the benefits to hundreds of thousands of peoples’ lives.

What kind of people do you need for the study? How many people are you looking for?

We need around 230 people to take part in the study – both males and females to take part, who are aged 55 and above.

Participants also need to have a diagnosis of Alzheimer’s disease.

However, people do not have to have high blood pressure and even if they have people taking certain drugs for their blood pressure treatment they can still take part.

What does taking part in the study involve?

The study team plan to take images (scans) of participants’ brains using Magnetic Resonance Imaging (MRI) at the beginning and end of the study to measure whether losartan reduces brain shrinkage and memory problems in Alzheimer’s.

Over 14 months, participants will have approximately nine appointments (some at the start and end at their local hospital, but many can be undertaken at home if preferable). There are a few in quick succession at the start and then they thin out over time.

People take a pill every day for the duration of the study.

You can see if you are eligible for this study by signing up with Join Dementia Research today.

Where is the study taking place?

All across England, in a number of sites across Scotland and in Belfast Northern Ireland.

There are now 23 research centres in hospitals across the country looking for people to take part.

This includes research sites in Bristol, Exeter, Torquay, Oxford, Manchester, Newcastle, Norfolk, Sheffield and many more (visit the study website for full list).

Is there a plan to do a study with people without Alzheimer’s disease?

There is evidence that the early changes in the brain that occur in Alzheimer’s disease can be laid down more than two decades before people have any memory impairment. There is therefore a movement to undertake studies in people with milder versions of cognitive impairment.

The theory behind this is that some people with early signs of memory impairment can go onto develop Alzheimer’s disease or other dementias.

However, there is an ethical dilemma not everyone who develops cognitive impairment will go onto develop dementia and it is not possible to give them a medication for an illness that may never appear. It’s a bit of a chicken and an egg scenario, however there is a lot of research effort currently underway to try

and address this issue of earlier and accurate diagnosis.

However, whilst these issues still currently remain, if RADAR is eventually found to reduce some of the impact of the disease on people when we look at peoples’ MRI scans.

It does potentially pave the way for more consideration of what drugs should and could be prescribed to treat high blood pressure in the future.This in itself might have a long term positive impact in reducing rates of Alzheimer’s disease going forward. However, our current study is only intended to prove a principal that losartan could be helpful, and much more research would be needed.

What are the challenges in taking forward this work?

Given that our study involves various teams at each given site including memory service staff, MRI centre staff and Pharmacy staff – it can take some doing to get individual research sites up and running and of course many of these staff are very busy NHS staff as well.

Recruitment of participants in studies continues to be a significant challenge for all research studies.

This can be due to people naturally being anxious about taking part in a study. It can also be, due simply to lack of large registers or lists of interested research participants around the country.

This is where the Join Dementia Research service will hopefully prove it’s real worth in the future and allow what seem to be a large number of very motivated people to access studies and be provided a choice of studies.

We are currently heavily reliant on the hard graft of very hard-working nurses in memory clinics and dementia research centres, and in some areas via primary care services, across the country to try and recruit people, this can also involve trying to bring in people who they have previously treated.

This is extremely challenging and time consuming.

Contacting people, who are registered upfront and keen to participate in research, would certainly help the recruitment to studies.

As the RADAR study opens across the country, we are hoping it helps us bring more patients forward, and hopefully participate if they are eligible to do so.

You can see if you are eligible for this study – and many others around the nation by signing up with Join Dementia Research today.