World Alzheimer’s Day: 3 recent good news – 09/20/2023 – Balance and Health

September 21st is International Alzheimer’s Day. The date was established to draw attention to a disease that affects the brain of more and more people.

According to the International Alzheimer’s Disease Association, one person develops dementia every three seconds. There are more than 55 million individuals affected by this condition, which affects memories and reasoning.

In Brazil, the Ministry of Health estimates that 1.2 million people live with some form of dementia — and 100,000 new cases are diagnosed each year.

Below, we have separated three good news that have recently been released about Alzheimer’s. They have the potential to change the way the disease is diagnosed, treated (and even understood).

1. Blood diagnosis

In summary, Alzheimer’s disease is marked by two main processes. In the first of these, there is an accumulation of a protein called beta-amyloid in the spaces between neurons.

Years later, these nerve cells are affected by another protein, known as TAU.

The result of this is the death of neurons, which leads to the progressive appearance of symptoms such as forgetfulness and difficulties in reasoning.

In recent decades, in the search for new treatments, scientists have learned two valuable lessons about Alzheimer’s.

The first is that the formation of beta-amyloid coils in the brain can be divided into a series of steps. They appear as monomers, evolve into oligomers and then form fibrils. With the advancement of knowledge, experts were able to understand in detail what happens in each of these phases.

Complicated names aside, in practice this means that different remedies can act at one stage or another in this process, which would supposedly lead to better or worse results.

“The question was how to interfere in this cascade of events, so that it could be interrupted before the condition became irreversible”, explains neurologist Fábio Porto, scientific director of the Brazilian Alzheimer’s Association – São Paulo Region.

The second lesson has to do with the need to diagnose the disease early. But if the idea is to treat individuals who haven’t even shown symptoms (or are still experiencing very mild discomfort), how do you know who has beta-amyloid aggregates forming in the brain?

The need to identify these individuals has led to a true revolution in Alzheimer’s screening.

Although even today, in doctors’ offices, the diagnosis depends on the evaluation of the health professional and the application of a questionnaire, more assertive tests are beginning to appear, which can quantify the toxic protein in the nervous system.

This can be done, for example, through imaging tests (such as PET/CT), CSF (the collection by puncture of a sample of the fluid present in the spinal cord and brain) and even blood.

And a test capable of detecting Alzheimer’s in the blood is now available in Brazil: in recent weeks, Grupo Fleury brought PrecivityAD2 to the country, which detects proteins capable of indicating the presence of amyloid plaques in the brain.

According to the company, the test results are comparable to other methods, such as PET, with the benefit of being less complicated and invasive.

“We believe that this is an important step towards the advancement of Medicine and the national health ecosystem. Early diagnosis of Alzheimer’s disease directly impacts clinical interventions related to the disease, something that results in a more favorable clinical outcome for the patient”, said Edgar Gil Rizzatti, president of the Medical, Technical, Hospitals and New Links Business Units of the Fleury Group, in a press release.

In an interview given to BBC News Brasil in July 2023, doctor Ricardo Nitrini, professor of neurology at FMUSP (Faculty of Medicine of the University of São Paulo), anticipated the arrival of such tests in the country.

“But the importance of early diagnosis is not, and should not be, to create stigma, but rather to allow advancement in methods that allow prevention. We can compare them to exams for early detection of breast or prostate cancer “, pondered the neurologist.

“The greatest advances in medicine always depend on very early diagnosis and prevention. And we are rapidly approaching this stage for Alzheimer’s disease,” he added.

2. New medicines

Research into a treatment for Alzheimer’s disease, the most common type of dementia, has gone a long time without major news. In the last two decades, no new medicines had been launched.

And it was not for lack of trying: more than a hundred candidates for new treatments were evaluated, but all of them frustrated the expectations of doctors, patients and families.

The scenario changed in 2021, with the approval of the drug aducanumab (from the pharmaceutical company Biogen) by the Food and Drug Administration (FDA), the United States regulatory agency.

It is worth mentioning that the release of this drug generated controversy in the scientific community, and subsequent requests for its use in other places (such as Europe and Brazil) were denied.

At the beginning of 2023, another medication against this type of dementia received the green light in the United States: lecanemab (from Eisai and Biogen laboratories). There is still no forecast of when it will arrive in Brazil.

And another option may be on the way: at the 2023 International Conference of the Alzheimer’s Association, held in the Netherlands, the positive results of studies with donanemab (Eli Lilly) were presented, which was able to slow the progression of the disease’s symptoms.

On the one hand, recent advances were celebrated and renewed hope, by indicating ways to at least delay the loss of memories and reasoning.

The idea of ​​using monoclonal antibodies such as aducanumab, lecanemab and donanemab to “sweep” beta-amyloid from the brains of Alzheimer’s patients emerged as an attempt to stop the disease from progressing.

In the world of dementia, however, the first tests with these drugs ended up frustrated. Some previous versions of monoclonal antibodies were able to clear beta-amyloid from the nervous system, but this did not translate into clinical improvements among volunteers.

In other words: their brains even had less of this toxic protein, but the impacts on memories and thinking continued to advance uncontrollably.

But then experts had another idea. Alzheimer’s is a slowly progressive disease — and there is a window of years or even decades between the start of beta-amyloid accumulation and the appearance of the first symptoms.

What if the medicines were used precisely at this stage, classified as mild cognitive impairment or early dementia? This is precisely what was tested, with relative success, with lecanemab and donanemab.

Tests with lecanemab, for example, involved 1795 participants with mild dementia. Half of them received the medicine, while the other portion took a placebo, a substance with no therapeutic effect. Everyone underwent examinations and cognitive tests to compare the results.

At the end of the 18-month trial, the group that used this monoclonal antibody had less beta-amyloid and showed a “moderately smaller decline in measures of cognition and function” compared to those who took a placebo.

With donanemab, the scheme was similar: 1,736 volunteers divided into two groups (medicine versus placebo) followed for a year and a half.

The results also show a slowdown of up to 60% in cognitive decline in those who received the therapy.

But how to translate this information into practice?

“This reduction in decline means that patients who took the treatment worsened less than those who took placebo. But they did not stop getting worse”, responds Porto.

“It was possible to delay the progression of the stages of Alzheimer’s disease by around four to six months”, adds the doctor.

In other words: treatment with monoclonal antibodies worked as a kind of brake, which delayed the progression of Alzheimer’s to the most serious and disabling stages for an extra time.

“These medications definitely manage to substantially reduce amyloid deposits. This is unequivocal and indisputable. But we still have a modest clinical effect, which may be difficult to measure from an individual point of view”, analyzes neurologist Paulo Caramelli, full professor at the Department of Clinical Medicine at the Federal University of Minas Gerais (UFMG).

“For people who eventually use these medications, this is something that will need to be explained very well”, points out the doctor.

But these medications still raise certain concerns in the medical community, such as the fact that the results are considered “modest”, the side effects are “potentially serious” and the prices are “extremely high” — as you understand in detail in this report.

3. New understanding of the disease

Journalist James Gallagher, from BBC News, recently published a report on research carried out in the United Kingdom and Belgium that details how Alzheimer’s “kills” neurons.

For decades, this has been a mystery and a source of intense scientific debate.

In an article published in the journal Science, the team associated the abnormal proteins that accumulate in the brain with “necroptosis” — a form of cellular suicide.

The findings were described as “interesting” and “exciting” as they pave the way for new ideas for treating the disease.

Researchers from the United Kingdom’s Dementia Research Institute, at College London and KU Leuven universities in Belgium, point out that abnormal amyloid begins to accumulate in the spaces between neurons, leading to brain inflammation — something that is harmful to neurons. This would start to change your internal chemistry.

Tangles of TAU begin to emerge and brain cells begin to produce a specific molecule, called MEG3, which causes their death through necroptosis.

Necroptosis is one of the methods our body normally uses to eliminate unwanted cells as new cells are produced.

The brain cells survived when the team managed to block MEG3.

“This is a very important and interesting discovery,” researcher Bart De Strooper, from the UK’s Institute of Dementia Research, told the BBC.

“For the first time we have a clue about how and why neurons die in Alzheimer’s disease. There has been a lot of speculation over the last 30 to 40 years, but no one has been able to identify the mechanisms,” said Strooper.

These answers came from experiments in which human brain cells were transplanted into the brains of genetically modified mice.

The animals were programmed to produce large amounts of abnormal amyloid.

Professor De Strooper says the discovery that blocking the MEG3 molecule can postpone the death of brain cells could pave the way for an “entirely new line of drug development”.

However, this will take years of research.

Tara Spiers-Jones, professor at the University of Edinburgh and president of the British Neuroscience Association, said “this is an interesting paper.”

She says the study “addresses one of the fundamental gaps in Alzheimer’s research.”

“These results are fascinating and will be important for advancement in this field.”

However, she emphasized that “many steps are needed” before we know whether the findings can be used as an effective treatment for Alzheimer’s disease.

This text was originally published here.