“The development of tests and treatments has accelerated.”

The only request that Dr. Daniel Alcolea makes during the interview that follows is to express his gratitude to the volunteers with Alzheimer’s disease and without memory problems who volunteered for blood draws, MRIs and lumbar punctures. Thanks to them, a researcher from the Dementia Neurobiology Group at the Sant Pau Research Institute and responsible for the biomarker platform of the hospital’s Memory Unit has developed a biomarker that allows the diagnosis of this disorder with a simple blood test and is 95% effective.

An achievement in which research groups from the United States and Canada collaborated and which was published in a journal. JAMA Neurologyopens up opportunities to reduce delays in diagnosing Alzheimer’s disease, as the first drugs to slow the progression of the disease appear in Europe, as well as to identify memory problems linked to social conditions and improve clinical trials.

How do these biomarkers work?

This is a traditional blood test, such as where you look at glucose, cholesterol or uric acid. This measures the molecule p-tau217, a marker of what is happening at the brain level in people with the disease, which is close to 95% accurate.

How can a protein that appears in the brain “tag” the blood?

This is what makes it so difficult to get here. We have known for ten years that biomarkers can be found in the cerebrospinal fluid, which is in direct contact with the nervous system, but in the blood their concentrations are much lower. Further improvement of analytical methods was required to detect these concentrations, which are also dissolved in the magma of proteins coming from other organs of the body.

One of the problems with Alzheimer’s disease has been the difficulty of diagnosing it.

This is a radical change. Until recently, when a person came for a consultation, a diagnosis could only be made based on symptoms and the exclusion of other causes. For several years now we have had some markers that can be measured, but it is necessary to perform a lumbar puncture, which, although safe, is an invasive and more logistically difficult method. A blood test makes the task much easier.

Having an altered marker in the absence of symptoms does not allow us to know whether the disease will develop in 5, 10, or 15 years. This information is difficult to deal with. We’ll see if it appears in the future, but it’s not intended for that yet.

At what stage can Alzheimer’s disease be detected using this biomarker?

The goal is to use it for people who already have symptoms, but we know from longer studies, and we also see it here, that things change 15 or 20 years before symptoms appear. The fact is that using it without symptoms also has its risks, since we do not yet know what information can be transmitted. Having an altered marker in the absence of symptoms does not allow us to know whether the disease will develop in 5, 10, or 15 years. This information is difficult to deal with. We’ll see if it appears in the future, but it’s not intended for that yet.

Even if we don’t know when the disease will develop, wouldn’t it help to take preventative measures?

There is no preventative measure today that you cannot take now without knowing whether you have this biomarker. The recommendation is: if you want to prevent it, do it now. Stay physically and cognitively active, socialize, avoid or control vascular risk factors as much as possible, such as tension, cholesterol, diabetes, etc. These are general guidelines, you don’t need a highlighter to get started.

Currently, how long does the diagnostic process take on average and what are the consequences of these delays?

This largely depends on the region and how easy it is for you to access specialists. In many cases where symptoms are very mild, patients may spend months bouncing around primary care, referral to a neurologist takes some time, and at that point you start looking at definitive tests. Sometimes it can take six months to a year from the time a person reports memory complaints.

What consequences does this time have on the development of the disease and the patient’s quality of life?

Let’s start with the uncertainty of what is happening to you and the anxiety or sadness that this may create in you. It is true that today there are no treatments that change the progression of the disease, so there is no pharmacological intervention that will sooner or later change its course, knowing this, but it will happen very soon. Probably, in a couple of months we will have approval from the European Medicines Agency and we will see drugs (lecanemab) for which it will be important to make an early diagnosis.

However, there is still no one who can stop or reverse the progression of Alzheimer’s disease.

Both lecanemab and donanemab in the United States, or those coming along the same lines, are the first step. For the first time, these drugs were shown to slow the process over the course of the study, which was limited to a year and a half. So when we have more power and more ability to evaluate this progress with a little more perspective and other types of interventions can be added to their treatment, then we will see the extent of their effectiveness.

Until recently, we could not even make an accurate diagnosis of the disease, so it was diagnosed based on symptoms. Once we had the information, we saw that in most studies, up to 30% of patients did not have Alzheimer’s disease.

Some experts point out that there has been a lot of research into Alzheimer’s disease over the years, but little results that can be translated to patients. Is this a somewhat frustrating situation? Are you now seeing the results of these efforts?

To say it’s frustrating is to understate it (laughs). It’s very unpleasant, but it’s reality. Until recently, we could not make an accurate diagnosis of the disease, so it was diagnosed based on symptoms. When we received the information, we saw that in most of the treatments tested, up to 30% of patients did not suffer from Alzheimer’s disease. Now that we have reliable tools to make more accurate diagnoses, the development of tests and treatments has accelerated. These markers allow us to much better select clinical trial participants and treatment candidates.

What are the next steps after research is published?

There will be a process of rolling out and implementing this technology, with regulatory issues and certifications that will come into play, but it is very robust, the results are very good, and at our center we intend to implement it in the coming months.

In practice, how will your biomarker improve the lives of your patients?

This will allow us to get an answer to the question that we are asked when we come for a consultation: “What’s wrong with me?” Here at Sant Pau Hospital we do a lot of lumbar punctures and have a lot of experience, so I think our patients are well diagnosed, but having a marker in the plasma will mean that this can be extended to other centers. who may not have access to this type of evidence. This will greatly facilitate the procedure and make it more comfortable for the patient.

We have many consultations from people who complain about their memory, but what fails are other types of attention, concentration or planning functions that are closely related to mood, anxiety, stress or even depression.

For a disease that is usually long-term, is work being done to improve patients’ quality of life? At what point is this profit?

The disease has been lengthened because we are diagnosing it at much earlier stages and so mild that they are not really an everyday problem. These patients present with memory complaints but lead normal lives for many years, and interventions can be made to improve their quality of life or to plan what to do in the future when these decisions can no longer be made.

Do you notice that we are becoming more and more concerned about memory?

Fully. I’m a little afraid that this study or this type of news may be misinterpreted and that people will believe that any memory problem is related to Alzheimer’s disease, because this is a major concern. We live in a world where everything moves so fast, we don’t pay attention and sometimes confuse these problems with concentration, so I think the need for care will increase. Now in neurology there are already many consultations from people who complain about memory, but when assessing it and performing a test, other types of functions of attention, concentration or planning, which are closely related to the state of mind, do not work. , anxiety, stress or even depression. This is a fairly common reason for consultation, so it is important to have accurate markers.

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