Anti-Amyloid Therapy for Early Alzheimer’s Disease: Benefits & Treatment

• A new class of medications can help slow the progression of early-stage Alzheimer’s disease by reducing the buildup of amyloid protein in the brain.
• Not everyone with memory problems is suitable for this treatment. A confirmed Alzheimer’s diagnosis and a thorough risk assessment are required before treatment begins.
• The earlier Alzheimer’s is detected, the better the chance of accessing treatment options at the right time, especially for people with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease.

In the past, most Alzheimer’s medications focused on relieving symptoms to help maintain memory, thinking and the ability to carry out daily activities for as long as possible. However, they did not act directly on the key processes that cause brain cells to degenerate.

Today, there is a new option for Alzheimer’s treatment: disease-modifying medications (drugs that aim to change the course of the disease) for people with early-stage Alzheimer’s disease. These medications act on amyloid protein that has built up abnormally in the brain, so they may help slow the decline due to Alzheimer's.
However, this new class of medications is not a cure for Alzheimer’s disease, and it is not intended for everyone who experiences forgetfulness. Treatment can only be considered after a careful diagnosis and thorough evaluation, particularly to confirm that the symptoms are caused by Alzheimer’s disease and that the patient is still at a stage where the medication can be beneficial.

Alzheimer’s medications currently include both drugs that help control symptoms and a new class of drugs that aim to slow the progression of the disease. Each has different goals and plays a different role in treatment.

Whichever type of medication a patient receives, based on medical indications and suitability, they still need guidance on managing other health conditions that are risk factors for or commonly occur alongside Alzheimer’s disease. Cognitive rehabilitation, exercise, nutrition, sleep and family support are also important for effectively slowing the decline caused by the disease.

One of the causes of Alzheimer’s disease is the production and buildup of a protein called beta-amyloid in the brain. This protein is produced by the brain’s own nerve cells and is found only in people who will go on to develop Alzheimer’s disease. The buildup begins 10 to 20 years before a person starts showing signs of forgetfulness. Beta-amyloid does not dissolve in water, so it clumps together and settles into amyloid plaques (deposits of protein in the brain). These plaques trigger inflammation, cause nerve cells to die, and damage the brain’s networks, which later leads to brain degeneration.

Anti-amyloid therapy is a new class of Alzheimer’s medication that binds to various forms of amyloid protein and helps the body clear more amyloid from the brain. This reduces the brain changes associated with the progression of the disease.

It is important to understand that reducing amyloid does not restore brain cells that have already been damaged. The goal of treatment is therefore not to cure Alzheimer’s or bring memory back to how it was before. Instead, it aims to slow the disease so that patients can keep the abilities they still have for as long as possible.

The benefit of treatment may not be a rapid improvement in memory after receiving the medication. Rather, by slowing the disease, it can help patients continue to carry out daily routines, manage personal matters, hold conversations, make decisions, or take part in family life for longer than they would without the medication.

Research in people with early-stage Alzheimer’s disease found that certain anti-amyloid medications can slow the decline in memory, thinking and the ability to manage daily life by about 27% on average, compared with a placebo (an inactive substance), over 18 months.

The 27% figure does not mean that memory improves by 27% or that the disease stops progressing. Patients still experience the natural decline of the disease, but on average, the group that received the medication progressed more slowly than the group that received a placebo.

For this reason, before considering anti-amyloid therapy, doctors need to carry out a comprehensive assessment. This includes confirming the diagnosis and stage of Alzheimer’s disease, evaluating overall health, a brain MRI, and APOE ε4 gene status, as well as the risk of side effects, to determine whether the treatment is suitable for each patient.

Anti-amyloid therapy is not suitable for everyone with Alzheimer’s disease. Currently, treatment is intended for people with early-stage Alzheimer’s disease who have undergone a thorough diagnosis and suitability assessment.

• People who may be considered include those with mild cognitive impairment (MCI) due to Alzheimer’s disease. This is the stage before a diagnosis of dementia. Patients have noticeable memory problems but can still carry out their daily activities as usual.
• People with mild dementia due to Alzheimer’s disease who can still take care of their personal needs on their own.
• People with test results confirming amyloid pathology (abnormal amyloid buildup) in the brain, as shown by a PET scan or cerebrospinal fluid biomarkers for Alzheimer’s disease.
• People who do not have a risk of bleeding in the brain, are not taking blood thinners, and do not have a history of stroke within the past year, epilepsy, or a neurological or mental health condition that may affect their ability to make treatment decisions and cooperate with long-term treatment. This also includes not having an end-stage physical illness that may significantly shorten life expectancy.
• People who are able to receive the medication and have follow-up brain MRIs regularly, according to the treatment plan, to monitor for possible side effects.
• People who have a caregiver or someone close to them who can help observe symptoms and take part in treatment decisions.

At present, anti-amyloid therapy is not used as standard treatment in the following groups:

• People with no symptoms, even if amyloid protein is detected: there is not yet enough evidence that treatment benefits people at this stage.
• People whose forgetfulness is due to other causes: the medication targets amyloid, so it would not address the actual cause of their symptoms.
• People with moderate to severe Alzheimer’s disease: once brain cells have been extensively damaged, reducing amyloid protein may not offer the same benefit as treatment started in the early stages.

Mild cognitive impairment (MCI) is a condition in which memory, thinking, language, concentration or planning abilities decline more than expected for a person’s age, but the person can still take care of themselves and manage most daily activities. For example, they can still go out and about, and manage their medications and finances, but they may need to write more notes, take more time, or double-check things more often. If they begin taking medications incorrectly, making payment mistakes, getting lost or being unable to carry out important daily tasks, an assessment may be needed to determine whether the condition has progressed to dementia.

However, a diagnosis of MCI does not mean a person can start the new anti-amyloid medications right away. This is because MCI describes the level of impairment, not its cause. The condition can be caused by Alzheimer’s disease, stroke, depression, sleep problems or sleep disorders, thyroid disorders, vitamin deficiencies, side effects of medications or other conditions.

Before considering anti-amyloid therapy to slow the disease, doctors need to carefully investigate the cause and confirm that the patient’s MCI is truly due to Alzheimer’s disease.

Before starting anti-amyloid therapy, doctors must carry out a thorough evaluation to confirm that the symptoms are caused by early-stage Alzheimer’s disease and to assess safety before treatment. This decision is not based on memory and cognitive tests alone.

1. Memory and cognitive assessment
   The doctor will take a history from the patient and the people close to them, assess how the patient’s brain function and various cognitive abilities have changed, and use standardized cognitive assessments to evaluate memory, attention, language, planning, visuospatial skills (the ability to understand the position of objects and space around you) and daily functioning.
   A score from a single assessment is not enough to determine whether a patient truly has cognitive impairment, because age, education, language, vision, hearing, anxiety and physical condition on the day of testing can all affect the results. Further evaluation by a doctor is needed to confirm that the patient truly has cognitive impairment.
2. Looking for other causes of forgetfulness
   The doctor may order blood tests to check for other possible causes of cognitive impairment, such as vitamin B12 levels, thyroid function, liver and kidney function and electrolyte (mineral) imbalances. The doctor will also review all medications the patient is currently taking, because some types of medication can cause memory problems or reduced alertness.
3. Brain MRI
   An MRI helps identify other causes that can be seen on brain imaging, such as stroke, tumors or hydrocephalus (a buildup of fluid in the brain’s cavities). It is also used to look for signs of past bleeding, small spots of bleeding (microbleeds) or abnormalities of the brain’s blood vessels that may increase the risks of anti-amyloid therapy.
4. Confirming amyloid protein buildup
   There must be evidence that the patient has an abnormally high level of amyloid protein buildup. There are 2 standard tests used to confirm a diagnosis of Alzheimer’s disease: a PET scan (a type of brain imaging) or a test of amyloid protein levels in the cerebrospinal fluid (the fluid surrounding the brain and spinal cord). Blood tests that measure proteins related to Alzheimer’s disease are still used only for initial screening. If the results are abnormal, they must be confirmed with one of the standard tests above. In the future, blood tests may play a greater role in diagnosing Alzheimer’s disease.
   A positive amyloid test result alone is not enough. It must be interpreted together with the patient’s symptoms, level of functioning and all brain test results.
5. Genetic testing related to the risks of anti-amyloid therapy
   The doctor will offer testing for the APOE gene, a gene associated with the risk of developing Alzheimer’s disease. People who carry the APOE ε4 gene have a higher chance of developing brain swelling or spots of bleeding in the brain, which may occur during anti-amyloid therapy. This test helps the doctor assess the risks of treatment more clearly. People who carry two copies of the APOE ε4 gene have a higher risk of side effects from anti-amyloid therapy than other groups, especially brain swelling or bleeding spots in the brain. A doctor must therefore carefully evaluate them before considering this medication.

Anti-amyloid medications are are generally given through a vein (intravenous infusion). The medication may be given every 2 weeks for the first 18 months, then every 4 weeks after that. Patients need to come in for treatment regularly and be monitored during or after each infusion, especially in the early stages, because infusion reactions may occur. These can include fever, chills, nausea, headache, rash, difficulty breathing or changes in blood pressure.

The length of treatment varies from person to person. Treatment may continue long term, or stopping the medication may be considered once amyloid has decreased to a target level. The decision depends on the type of medication, treatment results, MRI results, side effects and the treatment guidelines in use at the time.

The 2 main side effects of this class of medication are Amyloid-Related Imaging Abnormalities (ARIA) and infusion-related reactions (IRRs).

Amyloid-Related Imaging Abnormalities (ARIA)

• ARIA are abnormalities that can be detected on an MRI. They fall into 2 main types:
• ARIA-E: brain swelling or a localized buildup of fluid in the brain tissue

ARIA-H: small spots of bleeding in the brain tissue or localized bleeding on the surface of the brain
Some patients who develop ARIA may have no symptoms, and the condition is found on MRI scans scheduled after treatment begins. However, some patients may experience confusion, headache, dizziness, nausea, changes in vision, unsteady walking, weakness in the arms or legs, abnormal speech or seizures. In severe cases, ARIA can be life-threatening.

If ARIA occurs, the doctor may continue the medication, delay a dose, pause treatment temporarily or decide to stop treatment, depending on the type and severity of the abnormality seen on the MRI, the patient’s symptoms and their individual risk.

Infusion-Related Reactions (IRRs)
An IRR is a reaction that may occur during or after intravenous drug administration. Symptoms may include fever, chills, nausea, rash, changes in blood pressure or difficulty breathing. For this reason, Therefore, close monitoring by a medical team is required during and after each infusion.
 

• People with multiple spots of bleeding in the brain found on an MRI
• People who have had bleeding in the brain or certain types of stroke
• People taking blood thinners or who have a high risk of bleeding
• People who carry two copies of the APOE ε4 gene, which increases the risk of ARIA
• People with poorly controlled high blood pressure
• People who cannot have a brain MRI or cannot attend follow-up appointments as scheduled
• People with serious underlying health conditions where the risks of treatment may outweigh the expected benefits

Having one of these factors does not necessarily mean the medication can never be used, but each case needs to be evaluated individually by a doctor. Patients should never stop taking blood thinners or their regular medications on their own in the hope of becoming eligible for this treatment.

If a patient receiving this type of medication develops stroke-like symptoms the emergency team needs to know about their treatment history, because in some situations giving clot-dissolving medication may increase the risk of bleeding in the brain. Carrying a card or treatment information with you at all times is therefore important.

The window of time when the new anti-amyloid medications are suitable is fairly limited. Patients must already have symptoms but still be at the stage of MCI due to Alzheimer’s disease or mild dementia due to Alzheimer’s disease. If you wait until memory, decision-making and the ability to manage daily life have declined significantly, you may be past the stage where there is evidence that this class of medication can help.

If you start to notice symptoms such as forgetting recent events, asking the same questions repeatedly, having more difficulty doing familiar tasks, making mistakes with money or medications, getting lost in familiar places or having more trouble finding the right words, especially when these happen often or represent a change from before, you should get an assessment. There is no need to wait until symptoms become severe.

Detecting Alzheimer’s disease at an early stage does not mean rushing to start medication. It means finding out early what is causing the symptoms and whether you are still within the window when options to slow the progression of the disease can be considered.

The earlier the assessment, the sooner your doctor can look for causes that may be treatable, confirm the diagnosis, assess risks and work with you and your family to plan the right care.

Learn more about the In-Depth Health Check-Up Program to Detect Cellular Degeneration and Dementia Risk Before Symptoms Appear and the Health Check-Up Program for Older Adults.