Alzheimer’s disease: Are new treatments really changing the game?

For decades, treating Alzheimer’s disease essentially meant trying to alleviate its symptoms. In just a few years, however, the landscape has changed. The emergence of anti-amyloid antibodies, which target one of the biological mechanisms underlying the disease, has for the first time opened the door to treatments designed to slow its progression.

But beyond this shift in paradigm, what does the evidence actually show? A review published in 2025 in the Journal of the Chinese Medical Association provides an overview of therapeutic strategies currently available or under development across the Alzheimer’s disease continuum.

1. Taking stock of the current evidence

The evolution of Alzheimer’s disease management was reviewed based on major clinical trials, systematic reviews, guidelines, and recent diagnostic criteria. The different therapeutic strategies were examined across the six stages of the disease continuum.

 The review covers established symptomatic treatments — acetylcholinesterase inhibitors and memantine — as well as anti-amyloid immunotherapies, treatments in development, the management of neuropsychiatric symptoms, and non-pharmacological approaches.

However, no systematic literature search strategy, formal criteria for study selection, or meta-analysis were described. The review therefore primarily provides a clinical and therapeutic overview, rather than a quantitative comparison of the efficacy of the different strategies.

2. Alzheimer’s disease is no longer considered only at the dementia stage

The first major change is that Alzheimer’s disease is now viewed as a continuum, extending from an asymptomatic biological phase to severe dementia.

Advances in biomarkers — amyloid PET, cerebrospinal fluid biomarkers, and plasma biomarkers — now make it possible to detect abnormalities associated with the disease even before dementia develops.

The review uses a classification comprising six stages: asymptomatic disease with positive biomarkers, subjective cognitive decline, mild cognitive impairment (MCI), followed by mild, moderate, and severe dementia.

This change in classification is more than semantic: the stage of the disease now partly determines the available therapeutic options.

3. Lecanemab and donanemab: What has changed?

Lecanemab and donanemab are two monoclonal antibodies targeting amyloid. Unlike conventional symptomatic treatments, they act on a pathological mechanism of the disease by reducing cerebral amyloid burden.

In the United States, they have been approved by the FDA for early-stage disease — MCI due to Alzheimer’s disease and mild dementia — following biomarker confirmation of amyloid pathology.

Pivotal trials have shown a reduction in amyloid burden and a statistically significant slowing of cognitive and functional decline.

But “slowing” does not mean “stopping.”

The clinical benefit is therefore considered “modest”, and is estimated to correspond to an approximately 6- to 12-month delay in cognitive decline in patients with early-stage disease. These treatments do not restore cognitive functions that have already been lost, nor do they cure the disease.

4. Efficacy comes at a cost: ARIA

Another important limitation is that these treatments are neither simple to administer nor without risk.

Anti-amyloid antibodies can cause amyloid-related imaging abnormalities (ARIA), including cerebral edema and hemorrhagic abnormalities detectable on MRI. The risk is particularly increased in carriers of the APOE ε4 allele.

Their use therefore requires careful patient selection, confirmation of amyloid pathology, and MRI monitoring.

There are also very practical constraints: repeated intravenous infusions, imaging surveillance, costs, and access to biomarkers. In other words, the efficacy observed in clinical trials does not, by itself, resolve the challenges associated with implementing these treatments in clinical practice.

5. What about before the first symptoms appear?

This may be where the next major step lies.

If amyloid accumulation begins several years before symptoms emerge, why wait until cognitive decline develops before intervening?

The rationale is compelling, but the clinical benefit has yet to be demonstrated. The A4 trial, which evaluated solanezumab in asymptomatic individuals with amyloid accumulation, did not show a significant cognitive benefit.

Other trials are now investigating whether newer immunotherapies can achieve better results. AHEAD is evaluating lecanemab and TRAILBLAZER-ALZ 3 donanemab at preclinical stages of the disease.

6. Established treatments have not disappeared

The emergence of immunotherapies has not made established treatments obsolete.

Acetylcholinesterase inhibitors — donepezil, rivastigmine, and galantamine — remain in use for symptomatic disease, while memantine continues to have a role in moderate-to-severe disease.

The shift therefore lies less in replacing existing therapies than in the increasing stratification of treatment according to disease stage: anti-amyloid immunotherapy for selected patients at early stages, symptomatic treatments during the dementia stages, alongside management of neuropsychiatric symptoms and non-pharmacological interventions.

7. After amyloid, tau?

Amyloid is not the only therapeutic target under investigation.

The tau protein, whose pathological accumulation is closely associated with neurodegeneration, is one of the major areas of research. Several compounds have been or are currently being evaluated, including antibodies and strategies designed to reduce tau expression or propagation.

 Other approaches, particularly those targeting neuroinflammation, are also under investigation.

So, are we entering a new therapeutic era?

Perhaps — but not yet an era of cure.

The arrival of lecanemab and donanemab represents an important shift: for the first time, treatments directly targeting amyloid pathology have demonstrated an ability to slow clinical decline in selected patients with early Alzheimer’s disease.

However, their benefits remain modest, their risks require close monitoring, and their use depends on accurate biomarker-based diagnosis and appropriate healthcare infrastructure.

The most profound change may lie elsewhere: Alzheimer’s disease is increasingly becoming a condition that clinicians aim to identify and treat earlier, according to its biological and clinical stage.

The question is therefore no longer simply, “How should dementia be treated?” Increasingly, it is: At what point along the disease continuum should treatment begin — and with what combination of therapies?  

About the author – Ana Espino
PhD in Immunology, specialized in Virology  
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions.