The fight against Alzheimer's enters a new era

Barcelona"In the next five years, the way we treat Alzheimer's disease could change completely. We must be cautious, yes, but we are also optimistic," says Juan Fortea, director of the memory unit of the neurology department at the Hospital de la Santa Cruz y Sant Pau. In the last three decades, the prognosis for patients has hardly improved, but significant advances have been made that now open the door to a period of hope for patients and their families. The arrival of the first treatments that slow the progression of symptoms and the effectiveness of new diagnostic tests, which with a simple blood test allow us to anticipate the onset and course of the disease, lay the foundations for a revolution against Alzheimer's. Now, an international group of 40 experts, including the Catalan researcher, have warned in a publication in The Lancet that these improvements must be accompanied by urgent changes to unlock their full potential and achieve a real paradigm shift in the fight against the disease.

In Europe, two drugs proven to slow the progression of Alzheimer's, Leqembi and Kisunla, have already been approved, but the path has been fraught with ups and downs. In both cases, the European Medicines Agency (EMA) rejected their approval during the initial review, but ultimately recommended them for a specific group of patients, allowing them only to those with one copy or none of the gene called APOE4. Member states are now negotiating with the pharmaceutical company to market the first drug (some, like Germany, are already administering it to their patients), and negotiations for the second are expected to begin as soon as it receives final approval from the European Commission. However, while the arrival of the drugs has been delayed in European countries, they have been administered for some time in other parts of the world, and experts warn that this delay will have consequences.

"Europe has already lost two years, and that doesn't come without a price. We can't stop these changes; now we have to decide whether to continue unraveling the problem or get to work," Fortea argues, who, along with his colleagues, is calling for an urgent reform of healthcare systems to deploy these drugs. When someone takes one of these drugs, they must undergo additional tests, such as MRIs, and visit specialists regularly, so hospitals and healthcare centers must be scaled to meet patient needs. This means monitoring more patients, performing more tests, and hiring more professionals to handle the increased activity. The countries that have approved it are already undergoing this transformation, while in Europe they are not, and the gap between them is growing. "The risk of inequality is extremely high," Fortea insists.

Albert Lleó, director of the neurology department at Sant Pau Hospital, adds that it is necessary to deploy detection channels between primary care and hospitals to detect people with Alzheimer's in the early stages of the disease, when the prognosis is better and they are more likely to be candidates for treatment. In his opinion, this also requires improving the current awareness of Alzheimer's among healthcare professionals. "There are professionals who think that senile dementia is part of aging or that the diagnosis is not important because there is nothing that can be done. This also happened 40 years ago with cancer, when doctors did not inform patients of the diagnosis, and look at now. We believe that this will also happen with Alzheimer's, but we are at the beginning," says Lleó.

Similar efficacy to other drugs

Alzheimer's is characterized by the unusual aggregation inside and outside neurons of a peptide (a protein fragment) called beta amyloid and the protein known as tabula. It is not known why this happens, but this is most likely what causes cells to break down and the brain to gradually atrophy. Lecanemab and donanemab, both used by Leqembi and Kisunla respectively, are antibodies that attack beta amyloid protein plaques and are targeted at people who have early symptoms of the disease, such as mild cognitive impairment and mild dementia, as well as the presence of cerebellar tumors. According to several studies, lecanemab slows cognitive decline in people with Alzheimer's by 27% and donanemab by up to 35%.

In this study, experts have compared the effectiveness of these treatments with other drugs and claim that both Leqembi and Kisunla can slow the progression of Alzheimer's disease to a level comparable to the effectiveness of other therapeutic strategies and cancer multiple. Of course, it must be taken into account that not everyone can benefit from new Alzheimer's drugs, as they have only shown benefits for those people in the early stages of the disease. Therefore, the authors also admit that these comparisons "should be treated with caution."

Despite these levels of effectiveness, the authors believe that the "high costs of medication, complex testing requirements, and lack of resources leave Alzheimer's patients behind." Therefore, they call for coordinated global action to ensure that scientific advances in the field of Alzheimer's disease are accompanied by healthcare, economic, and social reforms. The paper's lead author and professor at the University of Geneva, Giovanni Frisoni, argues that a concentrated societal effort in this direction will allow current and future patients to "fully benefit from the potential of the scientific and technological advances" that have occurred over the past 30 years.