London Bridge Hospital
27 Tooley Street SE1 2PR London
Amyloid-targeting therapies for the treatment of early-stage Alzheimer's disease
Amyloid-targeting therapies like lecanemab and donanemab help remove amyloid beta from the brain to slow the progression of Alzheimer’s disease in people with mild cognitive impairment or mild Alzheimer’s disease.
What are amyloid-targeting therapies?
Amyloid-targeting therapies are a disease-modifying treatment for Alzheimer’s disease. They are a type of treatment called a monoclonal antibody. These antibodies stick to harmful proteins so they can be removed by your immune system. Amyloid-targeting therapies work by targeting a protein in the brain called amyloid beta, an important protein involved in the progression of Alzheimer’s disease. By triggering your immune system to remove amyloid beta, amyloid-targeting therapies can help slow the progression of the disease.
It’s important to understand that amyloid-targeting therapies don’t cure Alzheimer’s disease. Instead, they are shown to modestly slow the rate of progression in patients with mild cognitive impairment (MCI-AD) or early-stage dementia caused by Alzheimer’s disease (mild AD). Although they have been demonstrated to delay the progression of the condition, this does not mean they will completely stop the disease’s progress or lead to an improvement in your symptoms. Your condition will continue to progress, although at a slower rate than if you are not taking the treatment.
There are currently two amyloid-targeting therapies approved by the MHRA for the treatment of MCI-AD or mild AD – lecanemab (sold under the brand name Leqembi) and donanemab (sold under the brand name Kisunla).
How can amyloid-targeting therapies help?
Both lecanemab and donanemad have been tested in large clinical trials to understand their safety and efficacy in patients with early Alzheimer’s disease. After 18 months of treatment, currently available amyloid-targeting therapies slowed the rate of disease progression by up to nearly one third.
So, what does this mean for you? This means that over 18 months of treatment, these amyloid-targeting therapies can delay the progression of your symptoms by up to six months.
Are amyloid-targeting therapies right for me?
Amyloid-targeting therapies are designed for patients in the early stages of Alzheimer’s disease. You might hear this stage of the disease referred to as ‘mild cognitive impairment’ or ‘mild cognitive decline’. If you’re in the moderate or late stages of Alzheimer’s disease, amyloid-targeting therapies aren’t suitable for you as they won’t be effective.
If you’re in the early stages of Alzheimer’s disease, you’ll have a few tests before your treatment to make sure it’ll work for you. These include a test to check your levels of amyloid beta and a test to check your APOE gene status. The tests are explained in a bit more detail below.
You won’t be able to access amyloid-targeting therapies if you have any other medical, neurological, or psychiatric conditions that aren’t under control. Amyloid-targeting therapies also aren’t suitable if you’re taking anti-coagulants (blood thinners). Your consultant will help you understand if you’re eligible for either of the amyloid-targeting therapies and answer any questions you may have.
What does treatment with amyloid-targeting therapies involve?
Before having an amyloid-targeting therapy, your neurologist will carry out a few tests to ensure it’s suitable for you. These include:
- A cognitive test and neurological exam to check which stage of Alzheimer’s disease you’re in
- A brain MRI scan
- An amyloid PET scan to make sure you have high levels of amyloid beta
- A genetic test to see how many copies of a gene called APOE4 you have. Amyloid-targeting therapies aren’t suitable for people with two copies of this gene as they increase the risk of brain swelling and bleeds (ARIA). You can find out more about ARIA below.
Choosing to start an amyloid-targeting therapy is a big decision to make. Your doctor will help with this decision by outlining the benefits and risks of the treatment, the safety and monitoring guidelines, and any concerns they may have. They’ll be there to help you decide if having an amyloid-targeting therapy is the best treatment decision, and your safety and health will be their top priority. You and your family should also consider both the benefits and the risks of this treatment, and if it’s right for you. Whatever decision is made, we’ll be here to support you, your carer, and your family.
Having an amyloid-targeting therapy will involve lots of visits to the hospital for infusions and scans. To help get you to the hospital and support you in the event of any side effects, it’s important that you’re joined by a carer or loved one. They should be with you for all your hospital visits and have a good understanding of both the benefits and risks of the treatment.
Once you’re at the hospital, the amyloid-targeting therapy will be given by an intravenous (IV) infusion into a vein in your arm. Each infusion takes around an hour. How regularly you have the infusion depends on which treatment you choose:
- If you have lecanemab, you’ll have an infusion every two weeks.
- If you have donanemab, you’ll have an infusion every four weeks.
You’ll take both treatments for up to 18 months. However, if you’re having donanemab, you might be able to finish treatment after 12 months if a PET scan shows the treatment has cleared sufficient amounts of amyloid from your brain.
You’ll have your infusions in one of our special infusion suites at London Bridge Hospital Private Care at Guy’s. Here you’ll be looked after by our expert medical and nursing staff, who’ll make sure your treatment is going well and that you’re safe and comfortable. If you have any concerns or questions during your treatment, let our team know and they’ll do their best to address them. Our team will be there to support you and your family throughout your treatment, from the initial tests through to maintenance treatment.
After the infusion, you’ll have an observation period in case of any side effects and to ensure you’re safe. This observation period will be a little longer for your first few infusions as this is when side effects are more likely.
During the first nine months of your treatment, you’ll have regular clinical reviews with your neurologist every two months to check up on your progress.
In the first 12 months of treatment, you’ll also have regular brain MRI scans to check for any swelling or bleeding in the brain. These are referred to as amyloid-related imaging abnormalities, or ARIA. You can find out more about ARIA and other potential side effects of amyloid-targeting therapies below.
Once you’ve finished your treatment, most of the amyloid beta plaques in your brain should have been cleared.
If you are having treatment with lecanemab, you’ll switch to a maintenance treatment. The frequency of your infusion will be reduced from every two weeks to every four weeks. This frequency is still enough to reduce the progression of your symptoms in the longer term. The risk of complications after this period is much lower, so you won’t need regular MRI scans, and you’ll have fewer clinical reviews. But to make sure you’re safe, we might still occasionally check for ARIA.
If you are on donanemab, your treatment will be completed at 18 months, and you won’t require any maintenance treatment after that.
If your symptoms carrying on progressing to the moderate stages of Alzheimer’s disease at any point in your treatment, we will recommend you consider finishing your amyloid-targeting therapy.
What are the risks?
Infusion-related reactions happen when your immune system has a reaction to the drug entering your veins, and can happen with lots of drugs given via infusion. These reactions can cause:
- Itching
- Fevers or chills
- Rashes
- Headaches
- Dizziness or lightheadedness
- Nausea or vomiting
- Shortness of breath
- Fast heartbeat
The majority of infusion-related reactions are mild. Most people who experienced infusion-related reactions only did so during their first infusion. After this, they’re much less likely.
As mentioned above, amyloid-targeting therapies can cause amyloid-related imaging abnormalities (ARIA). ARIA involve leakiness of the blood vessels in your brain leading to brain bleeding or swelling, or a combination of both. As these are much more common in people with two copies of the APOE4 gene, the MHRA has disallowed the use of amyloid-targeting therapies in this group of people in the UK. We’ll carry out a genetic test to make sure you have one or no copies of the gene before starting treatment.
The rates of ARIA vary according to the amyloid-targeting therapy you are on:
Lecanemab –
- Less than 1 in 5 people will develop a mild, asymptomatic ARIA
- Less than 1 in 50 people will develop symptoms
- Less than 1 in 100 people will have serious complications from treatment
Donanemab –
- 1 in 3 people will develop a mild, asymptomatic ARIA
- Around 3 in 50 people will develop symptoms
- Less than 1 in 50 people will have serious complications from treatment
In the majority of cases, ARIA are very mild and don’t cause any symptoms – the ARIA are only detected during a regular MRI scan. A small group of people taking an amyloid-targeting therapy develop mild symptoms which might require additional MRI scans. Only rarely does the treatment cause serious complications. If your ARIA is more serious, your amyloid-targeting therapy may be stopped.
As amyloid-targeting therapies can increase the risk of brain bleeding and swelling, you shouldn’t have these treatments if you’re taking strong blood thinners (anti-coagulants) to prevent blood clots. This also means that you won’t be able to take some stroke treatments (clot-busters) if you have a stroke whilst taking an amyloid-targeting therapy.
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This content is intended for general information only and does not replace the need for personal advice from a qualified health professional.