A few days ago, the European Medicines Agency approved a new drug to delay or slow down the progression of Alzheimer's symptoms, Leqembi (lecanemab), a treatment that was already approved in the United States in 2023. With this medication, and others in the pipeline, a new hopeful scenario opens up regarding the treatment of dementia symptoms to slow down their effects.
“This is a colossal challenge and a great opportunity,” says Dr. Pablo Villoslada, Head of the Neurology Service at Hospital del Mar and Director of the Neuroscience Program at the research institute, as well as Co-Director of the Barcelonaβeta Brain Research Center (BBRC), a research center of the Pasqual Maragall Foundation with Hospital del Mar. “The incorporation of Leqembi represents a challenge for the healthcare system,” adds the doctor, who spoke to La Vanguardia to discuss the current state of drug research and provide some recommendations and key points on the prevention and progression of Alzheimer's.
We are in a complete paradigm shift because Alzheimer's and neurodegenerative dementias were neglected”
What does the approval of Leqembi mean? What relevance does it have?
We are in the midst of a complete paradigm shift because Alzheimer's and dementia were neglected, they were stigmatized. “It's just old age,” “this happens with age”... So the elderly person stays at home, receives some care, and it is believed that there is nothing more to be done. We have been fighting for 10 years to change this. And change is achieved, for example, with this drug, which alters the course of the disease and how we treat it.
What does this medication consist of?
It goes through the vein, it's an antibody, and it eliminates a protein that accumulates like garbage within the brain, and over many years it causes damage. In Alzheimer's, two proteins accumulate, amyloid and the other, Tau. Amyloid begins to accumulate at a very young age, from the age of 40. There are people who have very good brain health and eliminate it well, they recover, and others who don't. Then, the other protein, Tau, begins to accumulate, and they start to harm the neuron. In the end, everything reacts poorly, there is inflammation, more neurons start to die, and that is Alzheimer's.
This drug (Leqembi) delays the symptoms of Alzheimer's. Let's enjoy our father, our mother more in their current condition”
This drug eliminates that protein...
The protein itself is good, but when it accumulates it becomes a waste and starts causing problems. This medication eliminates it, and it has been seen to slow down the progression of the disease. Let's remember that this is a condition that causes patients to lose their memory, to stop recognizing their family members, to have behavioral alterations... It slows it down for six months, as seen in studies over a year and a half. In the longer term, we will have to wait and see. A brain cleanup is performed, and the idea is for it to remain effective for years. In the long term, the protein may accumulate again, but maybe not for a long time. In other words, this drug has a certain effectiveness—not complete—it delays the symptoms. Therefore, we will be able to enjoy more time with our father, mother, in their current condition.
But it also has side effects that are not insignificant, from swelling to possible bleeding in the brain...
Those side effects require us to closely monitor the patients. While cleansing the brain, the drug can damage blood vessels and cause some inflammation or small bleeding in some cases. If this side effect is detected, the treatment is stopped and then it can be resumed. There have been a few cases with serious complications, but we are talking about elderly people with many other illnesses.
A blood test provides results equivalent to neuroimaging techniques for diagnosing Alzheimer's disease
We are trying to speed up the procedures as much as possible. Hopefully, by the end of 2025, we will start providing treatment to certain patients”
Who is it indicated for?
Not for everyone, but for those with mild cognitive impairment, which is the initial form, mild Alzheimer's. Patients who are already more advanced, with clear memory and behavioral problems, cannot receive this treatment because its efficacy would be low and the risk of side effects increases. There are also patients who have a gene, APOE4, in whom it cannot be administered either.
The Leqembi has now been approved by European authorities. When will it arrive in Spain?
First, the European Medicines Agency approves it, and then each country decides whether the National Health System will finance it and at what price. Next come the autonomous regions, which have just adjusted and negotiated a bit, and then the hospitals, which have also just negotiated. This process can take between one and two years. We are trying to speed it up as much as possible, and hopefully, by the end of 2025, certain patients will start receiving it.
Why, in your opinion, does this medication and this emerging scenario pose a challenge?
This represents a revolution, it implies a significant effort for healthcare systems. We have to completely change everything. Now, when families notice any memory complaints, they have to speak with their general practitioner, who must perform a quick memory test and refer us to memory centers or cognition units within neurology services. There is where we have a team of neurologists and neuropsychologists to continue performing tests; we can do a lumbar puncture, an imaging test such as MRI or PET, and then we make the diagnosis. Not all dementias are Alzheimer's, and the drug is only for this one. What is going to happen is the beginning of a revolution in treatments for dementias and neurodegenerative diseases.
It means that having drugs that act at the onset of the disease will require many early diagnoses. A protocol needs to be established for a large number of patients who were not being treated until now...
Memory centers will have to conduct many tests. We are talking about thousands of patients. Those who meet the requirements will be included in this protocol of taking them to the day hospital, administering the infusion every 15 days at first, then monthly, and performing several MRI scans... Setting all this up is what oncologists did 20 years ago, and cardiologists did 30 years ago. It's not something that can be done overnight, we need to prepare ourselves. This is what we are all doing on this path. That's why we have set up this brain health center between the Hospital del Mar and the Beta center of the Pascual Maragall Foundation.
What is going to happen is the beginning of a revolution in treatments for dementias and neurodegenerative diseases”
What signs of memory loss should prompt a visit to the doctor? This is a very common question within the family setting, “Is it normal for my mother to forget this?”
There are things that are normal and things that are not. Losing the memory of an elephant and the ability to recall people's names happens to all of us from the age of 50 onwards. Now, when a person begins to complain that their memory is failing, it's because they have a subjective experience that something is not quite right. This is called cognitive complaint. It already has a category, it is not a disease, we think it could be the prodrome, the presymptomatic phase. Behavioral changes, as of a certain age (when a person is no longer who they used to be); becoming disoriented; getting lost - they don't tell you, but they stop going to places -... In these cases, you should go to your primary care doctor.
The diagnostic methods today are also revolutionary... Do we already have a lot of information from a blood test?
Specifically, biomarkers will be part of the revolution, like analytics. We were performing a lumbar puncture, it was aggressive. But now we already have a blood test.
There are over 200 drugs (for Alzheimer's) in trials, so in the next 5 years we will have 3, 5, or 7, each with its own effectiveness”
“We are going to have...” Already? Now? Soon?
Yes, we at Hospital del Mar already do this, as well as some other centers in Barcelona and Spain. If your primary care physician soon performs the test and requests this analysis (it is not yet available in primary care), the results will indicate whether the risk is high, low, or intermediate. In these cases, patients will be referred to specialized brain health centers, where we will complete the assessment and, if confirmed, propose a treatment plan.
Treatment with these new drugs... Are more medications coming in the next few months or years?
Yes, there is one approved —the one we have discussed— and there is another pending approval, which is very similar. Before spring, there will be two approved drugs at the European Medicines Agency, they will come to the United States, and they will be gradually implemented. However, there are more than 200 medicines in trials, so in the next 5 years, we will have 3, 5, 7, each with its own effectiveness. Initially, many studies will have to be conducted, there will be changes, and little by little, we will focus more on the early stages of the disease. We will eventually reach a point where we will suggest treatment even when you are not yet sick, in order to prevent disease.
Diabetes, obesity, and hypertension are terrible and people are not aware of it. After a decade, they have ruined you”
The Lancet has extensively detailed the risk factors for Alzheimer's and other dementias to determine which lifestyle interventions have the greatest impact in preventing these diseases. It is a highly cited document. What factors would you highlight?
The first one is education. There are people who do not have studies or have not been mentally active, and this affects cognitive reserve. By midlife, you have deafness, smoking, obesity, hypertension... Cardiovascular problems make your brain weak and unable to eliminate these accumulated proteins, amyloid and tau. Diabetes, obesity, and hypertension are terrible, and people are not aware. After a decade, they have destroyed your circulation and problems begin, heart attack, stroke, and dementia.
What role does deafness play in these diseases?
Men, starting at 70, begin to lose their hearing and become isolated. Hearing aids are not covered by Social Security. This prevents them from socializing.
When you sleep deeply is when the brain cleanses itself. If you have little time to clean it, more protein accumulates, causing more brain damage”
You also specifically highlight insomnia as a risk factor...
From the age of 50 onwards, everyone starts to wake up around three or four in the morning and sometimes you can't fall back asleep. When you sleep deeply is when the brain gets cleaned. If you have a short time to clean it, more amyloid protein accumulates, more brain damage. Then you have tobacco, which is related to everything circulatory, and the issue of physical activity and mental activity. Physical activity means being active, moving. And the mental activity, above all, do you know what it is? Socializing.
Isn't doing Sudoku or playing video games for seniors, right?
This is the main issue we have in Spain. The elderly are very well cared for within the family, but they are much less active compared to other populations. And on a mental level, especially when it comes to socializing, because the most challenging thing for our brain is trying to understand another person, much more so than doing mathematics, physics, or writing a book. But if you always socialize with your family and friends, this is not a challenge. The real challenge is socializing in environments where there is stress. In Japan, you won't see an elderly person in the street because they are volunteering. In the United States, people are volunteering. The elderly population needs to be much more active.
At a mental level, the most important thing is to socialize, because the hardest thing our brain does is trying to understand another person”
But we have a very high life expectancy, 84 years according to Eurostat, the highest in the European Union.
In Spain, there are many elderly people, but it's not a matter of quantity of years, but of quality. We are not interested in having 90-year-olds; we are interested in having 90 or 85-year-olds who are in perfect health. It is necessary to dispel another myth: that with age, dementia is normal.
Isn't it true? Neuropsychologist Saul Martinez-Horta told us that senile dementia, as such, does not exist...
As we age, we lose some things: balance, an elephant's memory, perhaps a bit of hearing and vision quality (but you don't have to end up deaf or blind). Apart from that, there are 95-year-olds who are in perfect condition. And that's what we should aspire to. In other words, it's not quantity, but quality.
About physical exercise, we receive many messages that are sometimes contradictory: “walking is not enough”, “strength training is necessary”, “just half an hour of walking a day is sufficient”...
It's about moving, exercising throughout life, not starting late because if not you're not used to it. And as an older person, well, keep moving constantly, not being sedentary. Now it is recommended to exercise to strengthen the muscles, because otherwise they tend to weaken, affecting balance and causing falls. A fall is terrible, the most important thing is that the person does not fall or have a hip fracture.
Turning 65 doesn't mean you have to be sidelined from society, “don't bother me”. The baby boom generation is going to refuse and we are going to see empowered older individuals”
On a collective level, what can we do to ensure that older people live more integrated lives in society? According to you, this is key to their physical and mental health.
We have to make a call to citizen action - here, local governments can do many things - mobilize older people. Now there is the whole concept of age discrimination, ageism; just because you turn 65, they can't push you aside from society, “don't bother.” The baby boom generation is going to refuse to let this happen, and we will see empowered older people who, since they have voting power, politicians will finally have to start paying attention to them. But it has to be a citizen initiative to activate us to include older people, to give them a role to help them stay physically and mentally active.
