How have the new anti-amyloid therapies changed the treatment of Alzheimer’s disease?

For many years, the treatment of Alzheimer’s disease has focused primarily on alleviating certain symptoms and preserving cognitive abilities and independence for as long as possible.

That situation has begun to change.

The arrival of the first disease-modifying therapies, which target the build-up of beta-amyloid in the brain, introduces a possibility that did not exist until recently: to act on one of the biological processes characteristic of Alzheimer’s and slow its progression in certain patients.

This is neither a cure nor a treatment capable of restoring abilities that have already been lost. But it does represent a significant change. For the first time, there are medicines available that have been shown to slow the progression of the disease in carefully selected patients treated at an early stage.

For Dr Rocío García-Ramos, head of the Memory Disorders Unit at the Publio Cordón Memorial Hospital, the full significance of this breakthrough must be recognised. It is not simply a matter of having a new treatment. It also requires better diagnosis, the precise identification of which patients may benefit, and particularly careful monitoring.

From treating the symptoms to tackling the disease

Medicines traditionally used to treat Alzheimer’s continue to play an important role. They can help manage certain cognitive and behavioural symptoms and form part of a broader approach that includes exercise, cognitive stimulation, managing risk factors, and support for the patient and their family.

New anti-amyloid therapies aim to achieve something different: to target one of the mechanisms involved in the development of the disease.

This is why they are referred to as disease-modifying treatments.

The term warrants some clarification. Modifying the disease does not mean stopping it completely. What has been demonstrated so far is a slowing of cognitive and functional decline in certain patients; in other words, the disease progresses more slowly than it would without this treatment.

In a progressive disease, this difference can be clinically significant. The aim is to preserve for longer the abilities that the person still retains.

Dr García-Ramos believes that this is one of the messages that needs to be conveyed most clearly to patients and their families: the progress is real, but it must be viewed within the context of reasonable expectations.

What is beta-amyloid?

To understand how these treatments work, it is worth explaining what they are designed to combat.

The brain naturally produces a protein called beta-amyloid. In Alzheimer’s disease, certain forms of this protein can accumulate abnormally between neurons and form deposits known as amyloid plaques.

These plaques are one of the characteristic biological hallmarks of the disease, although they do not, on their own, explain the entire process.

Alzheimer’s disease also involves abnormalities in another protein, known as tau, as well as inflammatory processes, vascular changes and a progressive loss of neurons and the connections that enable different areas of the brain to work in a coordinated manner.

For this reason, reducing amyloid does not equate to eliminating the disease. It does, however, allow us to target one of its most studied and best-understood mechanisms.

What do lecanemab and donanemab do?

Lecanemab and donanemab belong to this new generation of treatments. They are monoclonal antibodies, that is, proteins designed to recognise specific forms of beta-amyloid and promote their removal from the brain.

Both have been authorised in the European Union for specific groups of patients with early-stage Alzheimer’s disease and confirmed amyloid deposition.

In the clinical trials leading to their authorisation, patients treated with these drugs showed, on average, a slower progression of cognitive and functional decline than those who received a placebo.

The difference is significant: the patient does not ‘improve’ in the sense of regaining lost abilities. The aim is simply to slow down the rate of deterioration.

Dr García-Ramos emphasises that this distinction must be made clear from the outset. Faced with a disease that for decades has had very limited treatment options, being able to influence the rate at which it progresses represents a step forward. However, the expected benefit must always be assessed on a case-by-case basis.

Can Alzheimer’s be cured?

Not at present. The anti-amyloid therapies currently available do not eliminate the disease or reverse the brain damage that has already occurred.

Their significance lies elsewhere: for the first time, they allow us to act directly on one of the biological processes underlying Alzheimer’s and, at the same time, demonstrate a clinical effect on the progression of the disease.

This opens up a different perspective.

For some patients, the aim may be to buy time in terms of functional ability and independence. We do not know in advance how much benefit each person will derive, nor will that benefit be identical in every case. But the possibility of modifying the course of the disease represents a substantial change compared with the situation just a few years ago.

Furthermore, the development of these therapies is driving much broader research. Amyloid is not the only target. Treatments targeting the tau protein, certain inflammatory processes and other mechanisms involved in neurodegeneration are also being studied.

Current therapies are therefore less a point of arrival than the beginning of a new phase.

A specific programme to assess and treat potential candidates

The introduction of these therapies requires a healthcare system capable of integrating diagnosis, patient selection, treatment administration and follow-up.

For this reason, the Publio Cordón Memorial Hospital has developed, within its Memory Disorders Unit, the Alzheimer’s Anti-Amyloid Treatment Programme, designed to assess, treat and monitor patients who may be candidates for these therapies.

The programme, led by Dr Rocío García-Ramos, is based on an individualised assessment and may include neurological and neuropsychological evaluation, brain MRI, confirmation of the presence of amyloid pathology using appropriate biomarkers, ApoE genotyping, and clinical and radiological follow-up during treatment.

Its aim is not merely to facilitate access to a new therapeutic option, but to rigorously determine which patients may actually benefit, at what stage of the disease, and under what safety conditions.

This approach to anti-amyloid therapies aptly summarises the shift currently taking place in the treatment of Alzheimer’s disease: having new medicines available is important, but it is equally important to know when to prescribe them, how to use them and how to support the patient throughout the entire process.

Can all patients with Alzheimer’s receive these treatments?

No. And this is one of the key issues.

The currently authorised anti-amyloid therapies are aimed at patients with mild cognitive impairment due to Alzheimer’s or with mild Alzheimer’s dementia, that is, people in the early symptomatic stages.

Furthermore, memory problems alone are not sufficient.

Forgetfulness and other cognitive difficulties can arise for many reasons: normal ageing, sleep disorders, anxiety, depression, certain medicines, metabolic disorders or other neurological conditions.

That is why, as Dr García-Ramos explains, the first question is not which treatment to use, but what is actually causing these cognitive changes.

The Memory Disorders Unit at the Publio Cordón Memorial Hospital carries out a specialised assessment aimed at distinguishing between changes associated with ageing, mild cognitive impairment and the various conditions that can lead to dementia. This involves a combination of medical history, neurological examination, cognitive tests, neuroimaging and, where indicated, various biomarkers.

Why early diagnosis is now more important than ever

Alzheimer’s disease does not begin when a person loses their independence.

The biological changes associated with the disease can begin years earlier and progress gradually until recognisable symptoms appear.

The term ‘mild cognitive impairment’ is used when there are objective changes in memory or other cognitive functions, but the person still retains a significant portion of their ability to function independently.

Not everyone with mild cognitive impairment has Alzheimer’s, nor will everyone go on to develop dementia. This is precisely why it is important to investigate the cause.

The emergence of treatments indicated solely for the early stages has added a new dimension to early diagnosis.

A few years ago, an earlier diagnosis primarily enabled us to understand the symptoms, start the available treatments, better manage risk factors and plan for the future. All of this remains essential. But today, in certain patients, identifying the disease at an early stage may also allow us to consider a therapy that can modify its course.

This is one of the most significant changes at present.

As Dr García-Ramos points out, the sooner we can recognise a neurodegenerative disease and characterise it correctly, the more options we will have for deciding what can be done at each stage.

When there are still only minor changes or concerns regarding memory, an initial assessment can help determine whether further investigation is necessary. To this end, the Memory Disorders Unit runs an Early Alzheimer’s Screening Programme.

From clinical diagnosis to more precise medicine

The emergence of these tools is changing the way we understand diagnosis.

We still need to listen to the patient, find out how their symptoms have developed, carry out a neurological examination and assess memory and other cognitive functions. But now we can ask one more question: what is happening biologically in the brain?

This information allows us to distinguish more clearly between different diseases and is particularly relevant when there is a treatment targeted at a specific mechanism.

The innovation lies not only in having a different medicine available. It also lies in the fact that, to use it correctly, we need to know much more precisely which disease the patient has, what stage it is at, and what risks it presents. That is the point of talking about increasingly personalised medicine.

What is the ApoE gene and why is it tested before treatment?

Before prescribing an anti-amyloid therapy, it may be necessary to test for a gene known as APOE.

We all have this gene, and there are different variants. One of these, known as ApoE ε4 —‘epsilon four’—, is associated with a higher risk of developing Alzheimer’s disease and also with a greater likelihood of experiencing certain adverse effects during treatment with anti-amyloid therapies.

Having this variant does not mean that a person will necessarily develop Alzheimer’s, nor does it, on its own, allow for a diagnosis of the disease. Its significance in this context lies elsewhere: it helps to better assess the safety of the treatment.

Every person has two copies of the APOE gene, one inherited from each parent. The current authorised indication in Europe for these therapies takes into account precisely how many copies of ApoE ε4 the patient has.

For Dr García-Ramos, this is a good example of how clinical practice is changing. It is not enough simply to know the diagnosis; it is also necessary to understand certain individual characteristics before deciding whether a treatment is appropriate.

What are ARIA and why are MRI scans carried out?

Anti-amyloid therapies can cause a characteristic adverse effect known as ARIA.

The term is an acronym for ‘amyloid-related imaging abnormalities’ and refers to changes that may appear on brain imaging scans during treatment.

In some cases, there may be a temporary build-up of fluid in certain areas of the brain. This is known as ARIA-E. In other cases, small areas of bleeding or deposits related to previous bleeding may be observed. These are known as ARIA-H.

Many of these abnormalities do not cause symptoms and are detected precisely through follow-up MRI scans. In some patients, headaches, confusion, dizziness, visual disturbances or other neurological symptoms may occur. Less frequently, more serious complications may arise.

For this reason, these treatments require specific monitoring.

Dr García-Ramos approaches this issue from a very practical perspective: understanding the risk allows for better patient selection, the establishment of appropriate monitoring protocols, and swift action when an abnormality arises.

It is not a question of downplaying potential adverse effects or causing alarm. It is a question of incorporating them transparently into the therapeutic decision-making process.

Why these therapies require specialised monitoring

Before starting treatment, it is necessary to confirm that the patient meets the appropriate clinical and biological criteria. Thereafter, structured follow-up must be carried out, including clinical check-ups and MRI scans at specific intervals.

The process may require coordination across several disciplines: neurology specialising in cognitive disorders, neuropsychological assessment, diagnostic imaging, biomarkers, genetic testing, hospital management and ongoing clinical monitoring.

In certain cases, the appearance of an abnormality on an MRI scan may necessitate delaying administration, temporarily interrupting treatment or reconsidering its continuation.

This is why Dr García-Ramos emphasises a key point: the treatment process begins long before the first dose is administered.

The quality of treatment depends as much on the medication as on the ability to diagnose correctly, select the right patient and support them throughout the entire process.

So, what can we really expect from these therapies?

We can expect more than was possible a few years ago, although still not quite as much as we would like.

For the first time, there are treatments capable of targeting one of the biological mechanisms of Alzheimer’s and slowing its clinical progression in certain patients.

We cannot know in advance how much benefit a particular person will derive. But we do know that the landscape has changed.

Today we have better tools to detect and characterise the disease; we can identify more precisely which patients are eligible for certain treatments; and it is becoming possible to intervene in the progression of Alzheimer’s in its early stages.

This progress allows us to speak of hope without exaggeration.

Alzheimer’s remains a complex and, for the time being, incurable disease. But we are no longer exactly where we were a few years ago.

A new era in the treatment of Alzheimer’s

Anti-amyloid therapies represent one of the most significant changes in the treatment of Alzheimer’s in recent years.

Their importance lies not only in the medicines currently available, but also in the wider changes they are bringing about: early diagnosis, the use of biomarkers, the individual selection of patients and the way in which follow-up care is organised.

For Dr Rocío García-Ramos, head of the Memory Disorders Unit at the Publio Cordón Memorial Hospital, this new phase requires combining two approaches that are not incompatible: confidence in scientific advances and rigour in their clinical application.

For people who are beginning to notice persistent changes in their memory, language, orientation or other cognitive abilities, the message is not that every instance of forgetfulness should be a cause for concern.

It is this: when there are sustained and progressive changes, investigating them in good time allows for a better understanding of what is happening and, if a disease is present, provides more information and more options for deciding how to manage it.

And for those receiving an early-stage diagnosis of Alzheimer’s, treatment options are evolving.

Anti-amyloid therapies are not yet the definitive solution that patients, families and doctors are hoping for. But they do provide initial evidence that it is possible to intervene in the biology of the disease and alter part of its progression.

In the case of Alzheimer’s, this marks a turning point.

Informative medical content

This content is for general information purposes only and has been prepared solely for informational purposes. It is not a substitute for an individual medical assessment and should not be used to establish a diagnosis or decide on a course of treatment.

The prescription of therapies to modify the course of Alzheimer’s disease requires a specialist assessment, diagnostic confirmation and an individual evaluation of their potential benefits, risks and monitoring requirements.

If you experience symptoms of memory loss or other cognitive changes, please consult a qualified healthcare professional.

The information in this article is provided for general awareness and does not replace an individualised medical assessment.