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A Cochrane review has concluded that donanemab (Kisunla; Eli Lilly) and lecanemab (Leqembi; Eisai) — among other amyloid‐beta‐targeting monoclonal antibodies for Alzheimer’s disease (AD)-related dementia — are probably not effective for mild cognitive impairment or mild dementia.
Publishing their findings on 16 April 2026, the review authors analysed 17 studies with a total of 20,342 participants, which included measurement of outcomes at 12, 18, 24 and more then 24 months of treatment.
“Amyloid‐beta‐targeting monoclonal antibodies probably result in little to no difference in functional ability as measured on the ‘ADCS‐ADL’ (Alzheimer’s Disease Cooperative Study — Activities of Daily Living) scale,” they noted.
The review authors added that, based on their review, any effect on cognitive function and dementia severity at 18 months was “trivial” and that “on functional ability, it is small at best”.
“Successful removal of amyloid from the brain does not seem to be associated with clinically meaningful effects in people with mild cognitive impairment or mild dementia due to AD,” they added.
The review authors also found that, at 18 months, amyloid‐beta‐targeting monoclonal antibodies probably resulted in a small absolute increase of amyloid‐related imaging abnormalities related to oedema (ARIA E).
However, they said that most studies “did not separate people with symptoms of brain swelling and microbleeds from those in whom these effects were only visible with a scan”.
“[This] reporting gap leaves patients without the information they need to understand the seriousness of potential unwanted effects,” they added.
The authors went on to recommend that future studies should “report more transparently on the impact of ARIA”, as it is not currently possible to “truly know the clinical impact” of these.
They concluded that further research into disease‐modifying treatments for AD should focus on other mechanisms of action.
However, experts have criticised the Cochrane review for including failed drug trials.
Richard Oakley, associate director of research and innovation at the Alzheimer’s Society, said: “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 AD.
“It’s essential that we interpret this review with nuance and avoid taking a sledgehammer to decades of pioneering scientific study.“
Sir John Hardy, vice president of Alzheimer’s Research UK, commented: “Lecanemab and donanemab have shown us that slowing AD is possible, representing genuine progress. 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.”
The National Institute for Health and Care Excellence is currently consulting on a third draft of guidance for donanemab and lecanemab, having previously rejected the drugs for use on the NHS three times — a decision that has been appealed by the manufacturers. The drugs are licensed for adult patients in the early stages of AD.
