Alzheimer’s has advances in diagnosis, but cure is still seen as utopian

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More than 140 clinical trials on Alzheimer’s disease are underway around the world today and over 200 have already been completed, according to the international Clinical Trials platform. The cure, however, is still seen as something very distant, almost utopian.

According to experts on the subject, the most reasonable thing is to expect an increasingly early diagnosis, in addition to better control of the neurodegenerative disease through more effective drugs or a combination of therapies.

Data from the International Alzheimer’s Association point out that the disease represents the seventh cause of mortality in the world and one of the longest and most expensive. It is estimated that only 25% of cases of dementia are diagnosed. In low-developing countries, it is less than 10%.

There is a search for simplified methods capable of identifying earlier the disease markers in the brain: the beta-amyloid and tau protein plaques.

The accumulation of these proteins in brain tissue, which begins 10 to 15 years before the onset of symptoms of the disease, leads to atrophy of certain areas of the organ. With early diagnosis, it would be possible to adopt preventive measures and treatments that delay the development of dementia.

The identification of these proteins has been carried out in recent years through measurements of cerebrospinal fluid (spine fluid), but two new, less invasive allies have recently emerged: amyloid PET, a tomography that measures the volume of beta-amyloid plaques in the brain, and a blood test that uses a technique (mass spectrometry) that seeks to detect two types of beta-amyloid protein.

Such exams are only available in the private network, and the indication is still viewed with caution by neurologists who are on the front lines of Alzheimer’s patient care.

“Talking to the patient, applying tests [cognitivos], ruling out the hypothesis of some other brain alteration with tomography or magnetic resonance imaging remains the most effective way to make the diagnosis of Alzheimer’s. The vast majority will not need these biomarkers”, says neurologist Ivan Hideyo Okamoto, from Hospital Albert Einstein.

Neurologist Rodrigo Schultz, president of the Brazilian Alzheimer’s Association, has a similar opinion. “These are still not very powerful instruments for diagnosis. The impression of the professional who knows how to listen well to the patient and to ask correctly is still much more significant”, he says.

Schultz says that there are case reports from colleagues who ask for a CSF examination, for example, but, based only on the results, diagnose Alzheimer’s in situations where the disease is not present. The opposite also occurs: the exam comes without alterations, but the person has Alzheimer’s.

Neurologist Felipe Chaves Barros, from Hospital Sírio-Libanês, also argues that the clinical view remains sovereign, but says that these tests may have more relevance in very early or atypical cases of Alzheimer’s, when there are doubts about the diagnosis.

For him, it is very important to develop tools that allow an early diagnosis. “This is essential for the person to reinforce physical activities, to start cognitive rehabilitation as soon as possible, when it is still a mild impairment, to maintain autonomy as long as possible without dependence.”

There are promises of other forms of diagnosis using artificial intelligence. Japan, for example, is testing whether it is possible to assess patients with suspected Alzheimer’s through speech, that is, using factors such as the speed and content of conversations between people in telephone conversations.

There is also a race for more effective treatments to control the disease. The cure for Alzheimer’s, according to experts, has become almost a utopia since there is no indication that the brain areas destroyed by the disease are able to regenerate.

The first drug as a therapy for Alzheimer’s, aducanumab, was approved in 2021 in the United States, but the results of clinical studies have been disappointing. In Brazil, Anvisa (National Health Surveillance Agency) did not approve the product.

Although the drug destroys beta-amyloid plaques, so far it has had little effect on improving the condition of people with the disease. “The community that treats Alzheimer’s disease is a little skeptical about the effectiveness of the treatment. Today it is only indicated for very early stages”, says Felipe Barros.

Biogen, the drugmaker that developed aducanumab, has committed to submitting a new clinical study of the drug. There are other clinical trials in development also targeting beta-amyloid plaques, but now testing patients in the early stages of the disease or even asymptomatic.

There are also other therapeutic targets being studied, for example, tau protein and oligomers, which are smaller structures that bind to synapses and promote biochemical changes that cause communication between neurons to stop working.

There are still other lines of research in early stages investigating neuroinflammation processes that lead to the degeneration of neurons. The role of oxidative stress has also been studied.

“From now on it will be a cascade, one study after another. These options already existed before, but they gained more body after the aducanumab ended. In four years, it is possible that the scenario has already changed a lot. We will have more answers”, says Rodrigo Schultz.

For specialists, it is very likely that, in the future, Alzheimer’s will be treated with combined therapies, which address several of the issues involved in the pathophysiology of the disease, such as what occurs in the treatment of tuberculosis or antiretroviral therapies against HIV.

At the moment, however, the disease is mostly treated with old drugs, approved almost 20 years ago, which slow down but do not stop its progress.

“In addition, a whole multidisciplinary care, with a physiotherapist, neuropsychologist, speech therapist and occupational therapist, ends up being more important than medication to take care of this patient”, says Felipe Barros.

For Rodrigo Schultz, the good news is that the concept of mild cognitive impairment, a phase that precedes dementia, is more widespread in society. “People are more attentive, they come to us with a complaint [de déficit de memória ou de linguagem, por exemplo]even though it’s functional, doing what it’s always done.”

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