The Publio Cordón Memorial Hospital is introducing a programme for new therapies to modify the course of Alzheimer’s disease

The Publio Cordón Memorial Hospital has developed, within its Memory Disorders Unit, a specific programme for the assessment and treatment of patients who may be candidates for new disease-modifying therapies for Alzheimer’s disease.

The introduction of the first antibodies targeting beta-amyloid opens up a new therapeutic possibility for certain patients with early-stage Alzheimer’s. Unlike the treatments traditionally used to alleviate certain symptoms, these medicines act on one of the biological processes involved in the disease and have been shown to slow its progression in carefully selected patients.

For Dr Rocío García-Ramos, head of the Memory Disorders Unit at the Publio Cordón Memorial Hospital, their arrival represents an opportunity that was not available just a few years ago. The specialist points out that, for the first time, it is possible to consider a treatment for certain patients aimed at partially altering the course of the disease, although she stresses that this possibility must be explained accurately and without raising expectations that the medicines cannot fulfil.

‘Slowing down’ the disease does not mean stopping it or recovering cognitive abilities that have already been lost. However, for some patients diagnosed at an early stage, it may mean having a therapeutic alternative that allows them to delay part of its progression.

This is precisely why, explains Dr García-Ramos, it is particularly important to identify the right patient and to do so at the right stage of the disease.

Lecanemab and donanemab: what these new treatments offer

Lecanemab and donanemab are currently authorised in the European Union for adult patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease, provided that there is confirmed amyloid pathology and certain clinical and genetic criteria are met.

Both are monoclonal antibodies that target beta-amyloid, a protein that accumulates abnormally in the brain in Alzheimer’s disease.

The evidence that paved the way for their clinical use comes from large-scale trials in patients with early-stage disease.

In the case of lecanemab, the phase 3 Clarity AD trial, published in *The New England Journal of Medicine*, included 1,795 people with mild cognitive impairment or mild dementia due to Alzheimer’s disease and evidence of cerebral amyloid. After 18 months, the treated group showed less cognitive and functional decline than the group receiving a placebo.

Donanemab was evaluated in the phase 3 TRAILBLAZER-ALZ 2 trial, published in JAMA, which included 1,736 patients with early symptomatic Alzheimer’s disease. The treatment also demonstrated a statistically significant slowing of clinical progression compared with placebo during the 76-week follow-up period.

For Dr García-Ramos, these results represent a significant shift because they introduce a therapeutic objective that differs from that of the symptomatic treatments available to date.

At the same time, she points out that the trial results describe average differences between patient groups and do not allow us to predict exactly how much benefit an individual will derive. Some patients may experience a slower progression of the disease, whilst others may derive less benefit.

For this reason, she considers it essential that discussions with patients and their families cover both the opportunities offered by these alternatives and their limitations.

The opportunity to intervene earlier

The emergence of therapies specifically targeting the early stages of the disease also changes the significance of early diagnosis.

For years, detecting Alzheimer’s disease at an earlier stage mainly enabled a diagnosis to be made, symptomatic treatment to be started, follow-up care to be organised, and certain needs of the patient and their carers to be anticipated.

Now there is an additional reason: the timing of the disease’s identification can determine whether a patient can access a treatment that alters its course.

As Dr García-Ramos explains, one of the most significant changes introduced by these therapies is precisely this concept of therapeutic window. Once the disease has reached moderate or advanced stages, these medicines are no longer indicated. Consequently, recognising and properly assessing early cognitive decline takes on a different significance.

This does not mean, the specialist clarifies, that every memory problem is Alzheimer’s, nor that everyone who notices instances of forgetfulness needs to undergo complex tests. The first step remains a specialised neurological assessment capable of determining when there is actually cognitive decline that requires further investigation.

For people who have begun to notice minor changes in their memory or wish to undergo an initial assessment, the Unit offers an Early Alzheimer’s Screening Programme, designed to identify whether there are any signs suggesting that further investigation is warranted.

A programme that begins before a decision on treatment is made

The programme developed by Memorial Publio Cordón is based on an individualised assessment at the Memory Disorders Unit.

The process may include neurological and neuropsychological assessments, a brain MRI scan and tests designed to confirm the presence of amyloid pathology using the appropriate biomarkers for each patient.

This confirmation is essential. European authorisation for both medicines requires evidence of amyloid pathology, as well as a clinical diagnosis consistent with mild cognitive impairment or mild dementia due to Alzheimer’s disease.

The ApoE ε4 genotype must also be determined. In the European Union, lecanemab and donanemab are indicated for people who do not carry this allele or who carry a single copy, but not for those who carry two copies, primarily due to the increased risk of certain treatment-related complications.

Where cognitive symptoms are present, previous test results are abnormal, or it is necessary to confirm and characterise the disease before considering treatment, the Alzheimer’s Diagnosis Programme enables these tests to be carried out, a diagnosis to be established, and the stage of the disease to be determined.

Dr García-Ramos explains that this selection phase should not be interpreted as a barrier to accessing treatment, but rather as an essential part of its safe use. The potential benefit offered by these medicines depends precisely on being able to identify those individuals for whom there is a reasonable expectation of benefit and to avoid administering them when the risks may outweigh that potential benefit.

Two treatments with different characteristics

Although lecanemab and donanemab share the aim of reducing the burden of beta-amyloid in the brain, they differ in their method of administration and in certain aspects of their use.

Lecanemab, marketed as Leqembi, is administered via intravenous infusion every two weeks. The European Commission granted its marketing authorisation in April 2025 for the selected population currently covered by its indication.

Donanemab, marketed as Kisunla, is administered via intravenous infusion every four weeks and was authorised in the European Union in September 2025. Its treatment strategy also allows for the possibility of discontinuing treatment once certain criteria for amyloid plaque clearance have been met.

For Dr García-Ramos, the existence of different alternatives makes it all the more important to avoid a simplistic view of these treatments. It is not simply a matter of choosing a medicine, but of assessing which strategy is most appropriate for a particular individual, taking into account their clinical situation, diagnostic tests, safety profile and monitoring requirements.

A treatment requiring specialist monitoring

One of the main risks associated with anti-amyloid treatments is what is known as ARIA, amyloid-related imaging abnormalities.

These can primarily present as oedema or accumulation of cerebral fluid —ARIA-E— or as small haemorrhages and deposits of blood components —ARIA-H—.

In the Clarity AD study of lecanemab, ARIA-E was observed in 12.6 per cent of treated patients, whilst in TRAILBLAZER-ALZ 2, it was recorded in 24 per cent of participants who received donanemab. The characteristics of the trials and their populations differ, so these figures should not be used to make a direct comparison between the two medicines.

Many of these lesions are detected during MRI scans without causing any symptoms, although some may be clinically relevant and there are severe cases.

For this reason, brain MRI scans form part of both the pre-treatment assessment and follow-up during treatment.

Dr García-Ramos believes that this aspect must be addressed with particular transparency with families. Patients need to be aware of both the potential benefit of the treatment and the commitment it entails: regular infusions, MRI scans, monitoring for possible symptoms and, in certain circumstances, modification or temporary suspension of treatment.

Explaining what slowing the disease down might actually mean

One of the most sensitive issues is communicating the results of clinical trials effectively.

In the Clarity AD trial, at 18 months, the CDR-SB score — a scale that assesses cognitive and functional aspects — worsened by an average of 1.21 points in the group treated with lecanemab and by 1.66 points in the placebo group. The difference between the two groups was 0.45 points. The full results can be found in the original Clarity AD publication.

In TRAILBLAZER-ALZ 2, donanemab also showed less deterioration on the clinical scales used over the 76 weeks of the study. The full trial is published in JAMA.

Dr García-Ramos emphasises that these data should not be interpreted to mean that a person will “improve by a certain percentage”. The patient continues to have a neurodegenerative disease and may still experience deterioration.

The aim is different: to try to ensure that this progression is slower than it would have been without treatment.

For some people and their families, that difference may be significant. The assessment must always be made on an individual basis, taking into account not only the results of the studies, but also the patient’s functional status, their priorities, their expectations and their risk profile.

A decision in which the family is also involved

The decision to start a disease-modifying therapy should not be based solely on a diagnostic result. The Memory Disorders Unit regards providing information to the patient and their family as a fundamental part of the process.

Dr García-Ramos considers it important for the family to understand the aims of the treatment, what benefits can reasonably be expected, what the risks are, what monitoring will be required, and which aspects remain uncertain in the long term.

It is also necessary to understand the patient’s own preferences.

In a disease that progresses over many years, the possibility of slowing its progression may mean different things to different people. For this reason, the specialist advocates shared decision-making, in which scientific evidence is combined with the clinical situation and the priorities of the patient and their family.

A new phase in the management of Alzheimer’s

The authorisation of lecanemab and donanemab does not mean that a cure for Alzheimer’s is now available, but it does mark a new phase in its treatment.

The possibility of targeting one of the disease’s biological mechanisms reinforces the importance of accurate diagnosis, the use of biomarkers, and identifying patients at stages where a disease-modifying therapy may still be considered.

For Dr García-Ramos, this is probably one of the key messages that patients and their families need to be aware of at present: new options are available and, in certain cases, they may offer a therapeutic opportunity that did not exist before; however, that opportunity depends on making a correct diagnosis, intervening at the right stage, and carefully weighing up the benefits and risks.

The programme developed by the Publio Cordón Memorial Hospital within its Memory Disorders Unit is structured around this new approach: specialised neurological assessment, diagnostic accuracy, confirmation via biomarkers, rigorous selection of candidates, and clinical and radiological monitoring during treatment.

The advent of these therapies broadens the range of options available for managing Alzheimer’s disease. It also makes it more important than ever to know which patients may benefit from them, at what stage, and under what safety conditions.