Major Independent Review Casts Doubt on Benefits of Leading Alzheimer’s Drugs

A landmark analysis by the Cochrane Collaboration has found that the newest class of Alzheimer’s treatments offers benefits too small to make a real difference to patients — raising fresh questions for care homes about what lies ahead for residents living with dementia.

A wide-ranging appraisal of clinical trial data has concluded that a new generation of Alzheimer’s treatments targeting a protein called amyloid beta produces benefits so small they are unlikely to be noticed by patients or those caring for them.

Researchers examined data from 17 clinical trials involving seven drugs and more than 20,000 participants. The analysis covered both treatments that have received regulatory approval — lecanemab, sold under the brand name Leqembi and developed jointly by Eisai and Biogen, and donanemab, marketed as Kisunla by Eli Lilly — as well as five other compounds that did not succeed in trials.

The team was led by Dr Francesco Nonino, a neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences in Bologna, Italy.

The review concluded that across the body of evidence, effects on cognitive decline and dementia severity were either absent or so small as to fall below the threshold of clinical relevance. The researchers also flagged serious safety concerns, noting that both approved drugs carry a risk of brain bleeding and swelling, side effects that have already drawn scrutiny from regulators.

Dr Nonino noted that while earlier individual trials had produced results that were statistically significant, this does not automatically mean patients would experience a meaningful improvement. “It is entirely possible for a trial to detect a difference that is real in a mathematical sense but too small to matter in everyday life,” he said.

The review argues that the accumulated weight of evidence now points consistently in one direction: that removing amyloid beta from the brain does not produce a benefit sufficient to alter a patient’s lived experience of the disease.

However, Alzheimer’s Research UK has raised concerns with the findings “This review is attempting to paint an entire class of drugs with the same brush even though we know different anti-amyloid treatments can act in different ways,” says Dr Susan Kohlhaas, Executive Director of Research and Partnerships at Alzheimer’s Research UK.

“Lecanemab and donanemab have shown us that slowing Alzheimer’s is possible, representing genuine progress,” says Prof Sir John Hardy, UCL Institute of Neurology and Vice President of Alzheimer’s Research UK. “They are not perfect, but they have opened the door to a new era of treatment.”

“What matters now is that research into treatments is moving rapidly, and the pipeline of potential therapies is more diverse and promising than at any point in my career.”

“Anti-amyloid treatments will not be the whole answer to curing Alzheimer’s, and research is already moving towards a wider range of biological targets,” Dr Kohlhaas added . “But it’s not accurate to dismiss their impact as ‘trivial’, especially when the review’s analysis has clear constraints that limit what it can tell us.”

Importantly, the pipeline of new drugs being explored for Alzheimer’s disease is stronger than ever, with more potential treatments entering clinical trials in people.  Nearly 140 experimental treatments are being tested in more than 180 trials across the globe.