"You can discard the idea of a single illness with a single solution"

"You can discard the idea of a single illness with a single solution"

Farewell interview with Alzheimer’s expert Frans Verhey

08-06-2022

The most important theory has been shattered and dozens of years of research have not resulted in effective medication. Has the research into Alzheimer’s been a huge debacle? In the meantime, the risk of dementia has decreased by 13 per cent. Without medicine.

According to the dominant theory regarding the origin of Alzheimer’s disease, the most prevalent form of dementia, a specific type of protein - amyloid – accumulating between the neurons of the brain. As a result of these so-called plaques, communication between the cells becomes distorted, and they eventually die. This is the cause of Alzheimer’s.

If only it was that simple. The amyloid theory, which was popular in the nineteen-nineties, has lost considerable credibility. Tens of billions were invested in research into it, but results are poor. It is still not known what the amyloid protein does exactly, professor of Geriatric Psychiatry Frans Verhey recently stated in his farewell speech. Is it the cause of the disease or just a result of another damaging process? Or, does it actually protect against the disease? Because in fact, most elderly people with plaques in the brain do not develop Alzheimer’s.

Should we - looking at everything - conclude that the Alzheimer research had failed?

“No, you can’t say that. Initially the theory seemed plausible, everyone believed in it, I did too. But amyloid appeared difficult to research, it is not easy to recreate in the lab. You can study it in rats, but these animals don’t show signs of dementia. At one point, we managed to remove the amyloid via monthly injections into the brain, a technical tour de force, but patients didn’t benefit from it in any way.”

And still the hypothesis held strong.

“The theory was too big to fail. Huge investments had been made. There were brain institutes that completely focussed on amyloid, whole careers were based on it. It then becomes increasingly difficult to write it off. Some colleagues in the country, by the way, don’t appreciate that I am saying this. They still believe in the theory. It just comes down to timing, they say: you just have to intervene at the right moment when the plaques are formed, in the preliminary stages of dementia, and not when it has already accumulated. That has to do with the industry, it pays some groups handsomely to recruit patients for research.”

How does your group feel about it?

“It is very nuanced. You can’t say that the hypothesis is incorrect. People who are in the preliminary stages of the disease and who have amyloid in their brain, have a greater chance of developing Alzheimer’s. Yet, we have become more and more critical in Maastricht and for the past five years, we have no longer participated in amyloid trials. We feel that one shouldn’t put all one’s eggs in one basket, also because there are other options.”

Let’s first talk about the medication, which was approved in the USA last summer. Almost nobody believes in it.

“As far as I am concerned that is a real debacle. The FDA approved the medicine against the advice of a scientific committee. The worst decision ever, some committee members reckoned. The medicine doesn’t actually do anything. The effect is somewhere behind the decimal point, it is no good to you as a patient. It initially cost 56 thousand dollar per patient per year; after criticism, the price was halved. Insurance companies won’t reimburse the cost. It is not even permitted in Europa."

In the meantime, the chances of getting dementia have dropped by 13 per cent over the past ten years, without a single medicine.

"That is because we live healthier lives now, one of the options I spoke about. Many people have stopped smoking, and take blood pressure and cholesterol into consideration. The level of education plays a role too. The higher educated not only live healthier, but also use their brains more intensively, which is proven through the number of connections between the areas of the brain. But according to some scientists, this health gain is temporary; they point to all those Coke- drinking youths with obesity."

What needs to be done now?

"We, at any rate, need to continue to encourage people to live healthily. A couple of years ago, we had the Limburg campaign, 'We zijn zelf het medicijn’ (We ourselves are the medicine), together with GPs. They saw that the fear of dementia motivated people more to exercise and eat healthily. Alzheimer’s affects you personally, affects who you are."

Is that a conscious strategy, instilling fear?

"That wouldn’t be my preferred method. Alzheimer’s, as far as I am concerned, has already been portrayed as a spectre too much. You have to see it more like an ageing illness, which you could deal with differently. Since 2018, the World Health Organisation no longer views it as an incurable, scary brain disease against which nothing can be done, but as a handicap, which deserves support, just like someone in a wheelchair."

But it is in fact an incurable, scary brain disease, isn’t it?

"Originally, it comes from ageing, and yes, it leads to all kinds of complaints. But what the cause is.... A colleague of mine exposed a total of five different origin mechanisms, which were totally unrelated. So, most likely Alzheimer’s disease is a catch-all term for multiple 'diseases'. In dementia at a young age, for example, you see a different clinical picture. Alzheimer’s is at the most a vague syndrome, in which different symptoms often come together. It was wilfully framed as a scary disease in the nineteen-seventies in order to draw attention to it."

How would you feel if you received that diagnosis?

"As a handicap. I hope that people would support me, be kind to me and try to understand me. It all sounds very soft, but that is what you need as a patient."

Are you not more afraid to get Alzheimer’s than, say, heart failure?

"No, also because I see that the fear has been partly created. It is like blindness, very radical and limiting, but if it comes then it comes. And don’t get me wrong, it is no joke. But to be afraid beforehand; with the right help, you can have a meaningful life for years. We are doing a lot of psychosocial research into that, all with the aim to improve the quality of life."

What have you, as a scientist, learned about this whole matter?

"Modesty. If brain research has yielded anything, then it is how much more complicated everything is. You can discard the idea of a single illness with a single solution. I am also not one for overblown slogans, such as 'Rid the World of Dementia'. We are moving forward with small steps. And no, we won’t have a medicine in ten years’ time. It has been predicted each decade, but it has never come true."

That sounds purposeful.

"In a recent Zoom session with a number of Alzheimer researchers in the country, I asked the question again: who still believes in a solution for Alzheimer’s? Nobody raised their hands."

100,000 euro for Maastricht Alzheimer’s researcher

The brain of almost one in three seventy-year-olds shows major detrimental protein accumulations, so-called plaques. Not all of them have dementia, however. Maastricht neuropsychologist Willemijn Jansen is trying to find out why some people appear ‘more resistant’. She hopes this leads to treatment that can prevent or delay dementia. An approach that differs from many other Alzheimer’s research projects, which focus on the origin of this plaque. Last month, Alzheimer Nederland rewarded her work with a Young Outstanding Researcher Award, an annual talent prize for young researchers, worth 100,000 euro.

Currently, Jansen studies the more than two thousand proteins that can be found in the brain fluid of people with Alzheimer’s damage. “The question is whether we will find other (levels of) proteins in ‘resistant’ people than in patients suffering from dementia.” In doing so, she also looks into the effect of lifestyle, social behaviour and cognitive activity. Because of the prize money, she also hopes to be able to take the next step: detecting proteins in brain tissue of deceased persons, from who “we know that they didn’t have dementia, but also how they lived.”

Read the whole interview here

- DV

Who is Frans Verhey?

In 1986, he came to Maastricht from the university hospital in Utrecht and never left. In that year, Verhey and neuropsychologist Jelle Jolles together founded the first outpatient’s memory clinic in the Netherlands – by now there are a hundred. Along the way, his name and fame grew as a professor of Geriatric Psychiatry and dementia expert. He supervised 75 PhD students at the UM. Verhey will continue to work at the ‘Limburg Alzheimer’s Centre’, which he founded himself. And he will stay on at the UM for one day a week.

Photo: Joey Roberts

Categories: news_top, Science
Tags: alzheimer,frans verhey,research,study,alzheimer nederland,Geriatric Psychiatry,medication,plaques,instagram

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