Experts dispute Cochrane review on anti-amyloid Alzheimer’s drugs

A new Cochrane review of clinical trial data on different anti-amyloid treatments states these medicines show "no clinically meaningful benefit" for people with Alzheimer’s. Many researchers say the review has major limitations, and experts say those claims should not take away from the achievements of the latest Alzheimer’s drugs.

The review attempts to assess the impact of anti-amyloid drugs in Alzheimer’s, but much of the evidence it relies on comes from older experimental drugs that were discontinued due to trials that failed to show "meaningful benefit." Although the review included data from these trials, lecanemab and donanemab, the latest Alzheimer’s drugs licenced in the UK, are anti-amyloid drugs that have shown us that slowing Alzheimer’s is possible, representing genuine progress.

The review suggests that anti-amyloid treatments do not have a "clinically meaningful" impact. However, there is no agreed definition on what "clinically meaningful" means, and current clinical trial measures cannot always reflect what matters most to people with dementia. Families affected by dementia say that even a delay of several months in decline could provide valuable, meaningful time with loved ones.

The review also highlights the known risk of ARIA, which are changes to brain structure and swelling seen on MRI brain scans, but the studies it looked at did not consistently report how often this led to symptoms or how those symptoms were managed. The review itself does not fill an important gap in understanding how safe these drugs are in a healthcare setting.

Newer, longer-term evidence suggests that lecanemab and donanemab may deliver modest but sustained benefits beyond the 18-month limits of earlier studies, yet this emerging data is not reflected in the review. Longer term evidence gathered from routine healthcare settings is needed to understand how these treatments should be used in practice.

Amyloid-targeting antibodies have remained controversial. When the US Food and Drug Administration approved the first amyloid-β-targeting monoclonal antibody to treat Alzheimer’s disease in 2021, regulators advanced aducanumab on the grounds that it cleared amyloid plaques from the brains of people with the condition. But the drug had failed to slow cognitive decline in a clinical trial, and more than a third of people in the trial who received it had shown evidence of brain swelling that concerned doctors.

Research is already moving towards a wider range of biological targets. Companies have invested in tau, a protein that aggregates during disease, and researchers are looking for the next generation of disease modifiers, including metabolism, inflammation, and brain lipid handling. Nearly 140 experimental treatments are being tested in more than 180 trials across the globe.