The Cochrane Review – FAQ

Reframing the Evidence in Alzheimer’s Disease

1. What is the Cochrane review?
The Cochrane Collaboration is an independent group that reviews medical research to help summarise what is known about treatments. Its recent review looked at 17 clinical trials involving more than 20,000 people and seven different drugs designed to target amyloid, a protein linked to Alzheimer’s disease.

2. Why has this review caused confusion?
The review combined results from many different drugs developed over several decades.

This includes older treatments that failed, were withdrawn and are no longer used, alongside newer medicines such as Lecanemab (Leqembi) and Donanemab (Kisunla) that are currently approved and in clinical use today. Because these are very different types of treatment, the overall results are difficult to interpret clearly.

3. Does this mean Alzheimer’s treatments don’t work?
No. The review does not mean that current treatments do not work.

Modern disease-modifying therapies, including Lecanemab (Leqembi) and Donanemab (Kisunla), have been studied in large clinical trials and have shown they can slow the progression of Alzheimer’s disease in its early stages.

Over 18 month periods, Kisunla slowed cognitive decline by 35%  and Leqembi slowed cognitive decline by 27%.

4. Why is it important that older and newer drugs were grouped together?
Many of the older drugs included in the analysis were ultimately found not to be effective and are no longer used. When older, unsuccessful treatments are combined with newer, effective ones, it can make it harder to see the benefits of the latest therapies.

5. How many of the studies relate to current treatments?
Only two of the seven drugs included in the review are modern treatments used today.

These represent a small part of the total data, while most of the evidence comes from older drugs that are no longer in clinical use.

6. What benefits have been seen in clinical trials?
Clinical trials in people with early Alzheimer’s disease have shown:

Donanemab (Kisunla):

• Slowed cognitive decline by 35%  in the total study population, over 18 months
• With up to 60% slowing in  participants with Mild Cognitive Impairment (MCI)
• And even better results in participants with the mildest symptoms
• Reduced loss of daily function by 40%
• Removed amyloid plaque in the brain: in 1/3  of people by 6 months,  2/3 by 12 months and most of the remainder by 18 months of treatment.

Lecanemab (Leqembi):

Slowed cognitive decline by 27% over 18 months

• 49% less decline in EQ-5D-5L quality of life scores covering mobility, self-care, usual activities, pain and mood.
• 56% less decline in patient-rated QOL-AD scores, a dementia-specific quality of life scale assessing memory, mood, relationships and daily functioning.

These results are not a cure, but they represent an important step forward in treatment. And results are better than numbers stated above for individuals with more mild symptoms.

7. How do Leqembi and Kisunla work?
These treatments target toxic amyloid, a protein that builds up in the brain in Alzheimer’s disease.

By removing amyloid, the treatments are considered “disease modifying” therapies. This means they act on the underlying disease process and can slow progression, rather than only addressing symptoms

This is different from earlier medications such as donepezil, rivastigmine, galantamine and memantine, which are symptomatic treatments. These can help manage cognitive symptoms but do not alter the underlying disease course.

To illustrate the distinction using a cancer analogy:

Disease-modifying treatments are like chemotherapy, which targets the disease itself.
Symptomatic treatments are like painkillers, which relieve symptoms but do not affect the underlying condition.
8. Are these treatments a cure?
No. These treatments do not cure Alzheimer’s disease. However, they can help slow progression, which may allow people to maintain memory, independence, and quality of life for longer.

9. Are there any risks or side effects?
Yes. Like all medical treatments, these therapies can have side effects.

Some people may experience changes seen on brain scans, including swelling or small areas of bleeding. This  side effect is predominantly only  visible on MRI and is called Amyloid Related Imaging Abnormalities (ARIA ). It is unusual for individuals to experience symptoms related to ARIA. ARIA is monitored carefully by specialist teams throughout treatment.

10. Who can have these treatments?
These treatments are currently suitable for people in the early stages of Alzheimer’s disease, following detailed assessment by a specialist team.

11. Why are these treatments still approved if there is debate?
Regulators in the UK and other countries have reviewed the full clinical trial data independently.

Both lecanemab and donanemab were approved because they showed clear evidence of slowing disease progression in early Alzheimer’s disease, along with a well-defined safety profile.

12. What is the key message for patients?
Alzheimer’s treatment is changing.

While research continues to evolve, current evidence shows that newer disease-modifying therapies can slow disease progression in the early stages. This offers patients more time with preserved function, independence and quality of life.

These new treatments are most effective when started early, while cognitive symptoms are still mild. To meaningfully change the trajectory of the disease, early diagnosis and timely access to treatment are essential, helping to keep symptoms milder for longer.