New Cochrane review of amyloid targeting Alzheimer’s disease treatments

What is this review?

Cochrane reviews aim to analyse and draw conclusions about a particular health-related question. These reviews consider all the high-quality research on a topic and are often used by healthcare providers, policymakers, and patients to make informed decisions based on the best available evidence.

Published today, this review analysed amyloid-targeting drugs as a treatment for Alzheimer's disease. It looked at 17 clinical trials involving more than 20,000 people. These trials looked at drugs designed to remove amyloid, a protein that builds up in the brain in Alzheimer’s disease. Most of these treatments work by helping the brain’s immune system recognise and clear amyloid from the brain. 

The conclusion of the review was that the treatments had no clinically meaningful benefits.

Interpreting the review of amyloid-targeting treatments

The researchers have grouped together data from 17 clinical trials looking at a total of seven anti-amyloid drugs. They have combined data from a majority of unsuccessful trials as well as a small number of successful ones.  

Two of the seven drugs are lecanemab and donanemab, which are the only disease modifying treatments that have successfully slowed the decline of memory and thinking skills. Both have been approved by regulators in the UK and in many other countries around the world for people with early-stage Alzheimer’s disease. The UK regulator acknowledges a small but meaningful benefit for lecanemab and donanemab. 

The remaining five drugs looked at in the paper were either unsuccessful (12) or discontinued for other reasons (3) at late-stage trials and make up the other 15 trials.

The review also highlights safety considerations, looking at potential side effects of amyloid-targeting treatments such as including an increased risk of brain swelling and bleeding seen on scans It also highlighted limitations such as short follow up periods, inconsistent reporting of side effects and limited diversity in participants. These are widely recognised issues, and there is broad agreement across the research community on these points.

Continued research needed to improve treatments

Alzheimer’s disease is not driven by a single process and is associated with many other changes in the brain so it is unlikely that one treatment alone will be enough.

Future approaches will likely involve targeting multiple parts of the disease – using a combination of treatments.

Overall, this review provides a valuable summary of current evidence and reinforces the fact that it is critical other avenues of research to develop treatments are explored. 

But, we do not believe it means that treatments and research targeting amyloid should be abandoned.

Scientific progress is gradual, and continued research will be essential to improve treatments and develop more effective approaches for people affected by dementia.

Our response

Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said:  

It’s not the case that all amyloid-targeting drugs are ineffective. 

'This review’s conclusions make the picture look bleaker than it really is, as authors combined results for a majority of failed drug trials with a small number of more recent successful trials. This includes the trials for lecanemab and donanemab which the UK medicines regulator agreed bring a modest but meaningful benefit for people with early-stage Alzheimer’s disease.    

'It’s essential that we interpret this review with nuance and avoid taking a sledgehammer to decades of pioneering scientific study.  

'Alzheimer’s disease is highly complex and a combination of treatments will likely be needed to target a range of processes involved in its development. Anti-amyloid drugs are just one treatment avenue and not a silver bullet.'

We consider anti-amyloid drugs still to be a valid avenue to explore and optimise, reducing side effects, understanding their longer term impacts and ultimately bringing us closer to tackling Alzheimer’s for the millions of people affected globally.