Said Pascual Sanchez-Juan (Elche, 1973) who did not specialize in dementia because he had a case in his family that left a mark on him. He did it “by vocation”, because it was —and the rest— “a brain enthusiast“Even if his way of seeing has changed. Before, he observed it through the patient, as a neurologist at the hospital. Today, he tries to decipher it ‘from the inside’, with research.
He Scientific Director of the CIEN Foundation participates in EL ESPAÑOL on the occasion of World Alzheimer’s Day, celebrated every September 21. These dates are also special for him because four years have passed since he took over the leadership of this entity, dependent on the Carlos III Health Institute and supported by the Reina Sofía Foundation, in which some 800 brains from donors are waiting – who knows if one day – they will find the cure for Alzheimer’s disease.
It is still early to talk about it, but not too early to delay the progression of a disease that by 2050 could affect nearly 150 million people worldwide. In the United States, in fact, several drugs have already been approved with promising results. The latest, known as lecanemab, has not received approval from the European Medicines Agency (EMA).
Sanchez-Juan believes that This rejection represents a delay for Europe. He is confident that the final decision will go in the opposite direction. He is also hopeful for a new Global Alzheimer’s Plan to face the major problem that this disease represents, because currently “Spain is not up to the task” of the magnitude required.
Where is current research on Alzheimer’s disease going?
This is a big question. From the point of view of the mechanisms of the disease, of knowing its cause, we have made a lot of progress. We have not reached the level of detail to know why one person will suffer from it and not his brother. But we know that it is a complex process in which many factors intervene, such as for example certain genetic variants.
Great progress has also been made in diagnosis. Until recently, diagnosis was made by talking to the patient. But it has been found that this formula has very low reliability. So we need laboratory tests to properly characterize the patient. For example, we see that there are other pathologies associated with Alzheimer’s disease.
The third piece of good news is in the area of treatments. This year, the first anti-amyloid drug was approved in the United States, where thousands of cases have already been treated and it is used normally. We should be happy about that, because it is quite disappointing that for years not a single bill was approved. Now we have three in a very short time.
Is it bad news for Europe that the EMA has rejected this first anti-amyloid drug?
For Europe, it is a delay that it has not been approved; especially since in almost all countries where this issue has been raised, the opposite has happened. I think it is inevitable that it will eventually be approved in Europe. Most neurologists think that this is not a good decision.
The EMA’s argument was that the risk/reward balance was not sufficient. But it could have been approved more restrictively, limiting it to patients with a lower risk of side effects. With some simple mechanisms, they would significantly reduce the risk and could also carry out close monitoring.
One of the characteristics of lecanemab is its high cost. Do you think that inequalities could be generated regarding the treatment of this disease?
It is true that in the United States, health insurance covers 80%, and that is why it will surely have a bias. Although, unfortunately, this is common in a country like this. In Europe, if the drug is not finally approved, there may be a very wealthy population going to the United Kingdom or Switzerland to administer the drug.
Brain samples stored in the CIEN Foundation tissue bank.
Are you in favor of a diagnosis of Alzheimer’s being made several years before the onset of symptoms?
Making a diagnosis before the onset of symptoms is in no way justified today because we do not have drugs that modify the course of the disease and that have proven their use in these cases. Yes, it is true that there are already clinical trials in which it is being tested.
If it is shown that giving these drugs to an asymptomatic population but with pathology modifies the disease, then perhaps we should reconsider our decision. What we need to do now is to diagnose the disease in the early stages. And not wait until the patient develops dementia.
What are the first signs of Alzheimer’s disease?
Memory problems are the main indication of the disease. One of the first problems with a type of memory we call episodic is the difficulty in fixing short-term memory into long-term stores; that is, you don’t remember what you had for breakfast this morning, what you did yesterday, or you ask yourself repetitive questions. This is the most characteristic form of Alzheimer’s disease.
Some of the recommendations of experts to reduce the risk are to rest well, to exercise and to lead an active social life. In Spain, do we respect them?
Unfortunately, we have less and less of a Mediterranean lifestyle compared to what we had before. For example, we are famous for the siesta, but in Spain we often sleep little and sleep is very important. It is true, however, that we have a slightly more active life than other countries such as the United States.
But I wouldn’t say that we have a lifestyle that is particularly protective against Alzheimer’s. The Mediterranean diet is no longer predominant, now we eat like elsewhere. Despite this, we have a very high longevity rate. This is probably because we have good health care. It is also true that in the rural population, the lifestyle is healthier.
We all have to go to town.
Yes, in town, but with a family doctor nearby [se ríe].
Do you apply these recommendations yourself?
Yes, I wake up early and start the day after running for at least 30-40 minutes. For me, if I had to give just one piece of advice, it would be to exercise. Not only is it beneficial in itself and helps the brain, but it also regulates blood pressure, blood sugar or reduces inflammation. Exercise is the most cost-effective modular factor if you want to do something for your brain.
Training is also essential. As a father, I try to help my children generate this brain resilience as early as possible. In this regard, we know that languages are very important, being exposed to them from a very young age, as well as music, which is also good for the brain.
Do you think the population is aware of this disease, compared to others that have a more direct impact on the collective imagination?
No, the problem posed by neurodegenerative diseases is not sufficiently valued. This is perhaps because it is assumed that it only affects older people. But this is not always the case, I have treated patients from the age of 29. You can have Alzheimer’s disease at that age.
Now we are living longer and we are coming into better conditions. My grandmother will be 99 next month and she is doing very well. This will become less and less of an exception, so it will be more important to try to stop these diseases because of the real avalanche that will come. By 2050, it is estimated that about 150 million people worldwide will have dementia. It is outrageous.
Sample of the condition of a donor brain with advanced Alzheimer’s disease.
Does the arrival of this “avalanche” translate into a commitment to sufficient research in Spain?
No, we are not up to the challenge. In other countries, they have responded more. In the United States, for example, they invest a lot in research. In Spain, we are not up to the major challenge that this disease represents and, without a doubt, more investment in research should be made.
Would you say that investment has varied depending on which party has governed at any given time?
No, because it is a cross-cutting problem. In fact, there should be a pact. The magnitude of the disease is such that there should be a consensus, like the one reached with ALS. This is the main challenge that our society faces. But it is like in the movie about meteorites, we do not want to look at what is coming, but it is coming.
As long as there are cancers, will it be difficult to advance research against Alzheimer’s?
No, I don’t think it’s incompatible. Everyone has a disease and we all have to investigate. Obviously, cancer is a very morbid disease, but the unthinkable advances today allow it to be cured or become chronic. In the field of neurodegenerative diseases, I think we are starting to go down this path. Things that currently seem like science fiction to us, I am convinced that in a few decades they will become reality.
For example?
Delaying the progression of these diseases with treatments that modify the biology. Anti-amyloid drugs are the first step. But right now, there are many other very promising treatments being evaluated. If we use them together and in well-diagnosed patients, they will delay the progression of the disease and we can… I’m not saying make it chronic, but it will greatly prolong the onset of addiction.
This dependency is the real drama of families. A patient with cognitive disorders can be phenomenal for a long time, but when he begins to have difficulty performing daily tasks, that is when the big problems arise. That is why the ideal would be to treat them when they have the pathology but have not yet developed it. That they can live a long time and die of another cause with, at most, a slight forgetfulness.
