Alzheimer's: A mix of new and old therapies is needed to treat it.

The advent of new diagnostic tests and new monoclonal antibody therapies appears to be opening up new avenues for the treatment of Alzheimer's disease. At the same time, a group of experts warn in a series of three scientific articles published in The Lancet , these are "young" tools, whose great potential can only be fully exploited if, in parallel, all the diagnostic and therapeutic tools already available and consolidated over years of research continue to be adequately utilized.

Drugs pros and cons

In particular, two monoclonal antibodies, lecanemab and donanemab, have generated considerable enthusiasm due to their being the first to modify the course of the disease. However, they are at the center of debate due to their high price, the side effects they can cause, and the fact that currently only a small percentage of patients qualify for treatment.

"With this series of articles, we've tried to normalize this debate, emphasizing that these issues are not specific to Alzheimer's. These two monoclonal antibodies were developed according to the standards of all other monoclonal antibodies for other chronic diseases; there's nothing strange about that. What makes the discussion somewhat different are the social dimensions of the disease," Giovanni Frisoni , who coordinated the series published in The Lancet and is director of the Memory Center at Geneva University Hospital (Switzerland) and professor of clinical neuroscience at the same university, explained to Salute.

What are the new therapeutic possibilities?

Alzheimer's is the most common form of dementia and is estimated to account for 60-70% of the total number of cases, which exceeds 50 million worldwide. It's no surprise, then, that there's been a surge of excitement over the advent of drugs that experts call disease-modifying , precisely because they can slow the disease and perhaps temporarily stabilize it, though they don't completely halt its progression. We're talking about lecanemab and donanemab , two monoclonal antibodies designed to reduce the accumulation of beta-amyloid protein, which appears to be one of the triggers of Alzheimer's disease. The former was approved in 2023 by the U.S. Food and Drug Administration (FDA) and subsequently by the European Medicines Agency (EMA). Donanemab, on the other hand, was approved by the FDA in 2024 and the EMA is re-evaluating it following an initial negative opinion issued at the end of March 2025.

Evaluation of side effects

As anticipated, in addition to the positive effects on the disease's progression, a certain percentage of clinical trial participants experienced side effects, including serious ones, such as cerebral edema or hemorrhage. The authors of the new series therefore attempted to compare the costs (both broadly and narrowly) and benefits of the two new monoclonal antibodies with those of other biologic drugs developed for the treatment of certain types of cancer, multiple sclerosis, or rheumatoid arthritis. Although the comparison must be taken with caution, given that the diseases and patients involved are clearly different, what emerges is that lecanemab and donanemab, for example, lead to a reduction in the progression of Alzheimer's-related disability comparable to that seen in other studies focusing on monoclonal antibodies for the treatment of multiple sclerosis and rheumatoid arthritis.

A process that must take its course

The point, Frisoni argues, is that we shouldn't look at these two new tools as the only ones we can rely on from now on: "Let's not look at these innovations thinking that, on their own, they can be the solution. Instead, let's consolidate the knowledge already available and care for patients by making the best use of the tools we already have. Then, let's leverage this fertile ground, built on knowledge and experience accumulated over time, to implement these innovations."

Also because the two new monoclonal antibodies will need to continue to be studied to better understand whether they are suitable for all Alzheimer's patients or only for some, and in which conditions they most frequently lead to the development of side effects.

"This is a journey that has begun and I believe will continue inexorably, but we must accept that initially only a few patients will be treated," Frisoni continues. "And that's right; it would be madness otherwise." Only with time, he explains, will we be able to understand and "handle" them better, and even obtain second-generation ones that may be better tolerated. In short, we're still at the beginning of a process that certainly seems promising, but it must run its course.

Leveraging what we already have

In the meantime, we must remember what we already have at our disposal: "I'm referring to the appropriate use of medical history taking, neuropsychological tests, MRI, PET scans, and medications for behavioral disorders. These are all tools we've been using for years, and we understand them much better today than we did 30 years ago," adds the professor. "However, we must ensure they are fully exploited not only in the most specialized and leading clinics, but everywhere."

Psychoeducation of family members

An example of an approach that doesn't receive the attention it deserves, Frisoni explains, is psychoeducation for family members. This involves specific training for caregivers , aimed at providing them with the knowledge needed to best manage the behavioral problems that a large percentage of Alzheimer's patients tend to develop, which often have a significant impact on the quality of life of patients and their families: from irritability, to sleep disturbances, to apathy, to depression, and even full-blown psychosis.

"Psychoeducation is an intervention that requires a lot of energy and money," the expert concludes, "because it requires well-trained personnel who spend hours and hours with the family member trying to understand the circumstances under which the behavioral disorder develops, which environmental situations trigger it, and how they can be modified to reduce its frequency, or when and if it's necessary to resort to psychotropic drugs. It's an approach that requires daily, if not near-daily, monitoring, yet it can be highly effective."