A new major review has concluded that a class of drugs heralded as a breakthrough for Alzheimer’s disease offers patients only trivial benefits that are too small to be noticeable in daily life. The findings from the Cochrane collaboration, a globally respected body for analysing medical evidence, state that the effects of anti-amyloid medicines on cognitive decline are “either absent or consistently small” and fall “well below established thresholds for the minimum clinically important difference”.
The review’s findings: small numbers and side effects
The Cochrane review analysed 17 clinical trials involving 20,342 people with either mild cognitive impairment or early Alzheimer’s dementia. It included data on six drugs: the licensed treatments lecanemab and donanemab; the discontinued aducanumab; and three older drugs—bapineuzumab, crenezumab and solanezumab—which were abandoned after failed trials.
According to the authors, the combined effect of these drugs on measures of cognitive function and dementia severity after 18 months was “trivial”. Professor Edo Richard, a neurologist at Radboud University Medical Centre in the Netherlands and a review co-author, said the differences made were “far below the minimal effect that’s needed to be noticeable at all for patients and caregivers”.
The review also highlighted that the drugs likely increase the risk of swelling and bleeding in the brain, known as amyloid-related imaging abnormalities (ARIA). These were often visible only on scans and asymptomatic, though the long-term implications remain unclear.
Francesco Nonino, a neurologist and epidemiologist at Italy’s IRCCS Institute of Neurological Sciences of Bologna and another author, stated bluntly: “Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients.”
The crucial distinction: statistical vs. clinical significance
The central argument put forward by the review authors hinges on a key concept in medical research: the difference between a result that is statistically significant and one that is clinically meaningful. This point has become the core of the ensuing debate.
Francesco Nonino explained that while some early trials for these drugs showed results that were statistically significant—meaning the observed effect is unlikely to be due to chance—this does not automatically translate to a meaningful change for a person living with the disease. “It is common for trials to find statistically significant results that do not translate into a meaningful clinical difference for patients,” he said.
The researchers argue that the modest slowing of decline shown in some trials, when translated into the reality of a patient’s life, is simply too minor to be perceptible to them or their family. Professor Richard, who runs a dementia clinic, said he is honest with patients, telling them the benefit is “too small for patients and caregivers to notice” and that the treatment regime—requiring intravenous infusions every two to four weeks and regular scans—is “burdensome”.
Charities and experts challenge the conclusions
The review’s conclusions have been robustly challenged by leading dementia charities and independent experts, who argue its methodology paints an unfairly bleak picture.
Their primary criticism is that the review pooled data from successful and failed drug trials together. Dr Richard Oakley, associate director of research at the Alzheimer’s Society, said the authors “combined results for a majority of failed drug trials with a small number of more recent successful trials,” including those for lecanemab and donanemab, which UK regulators approved for showing a “modest but meaningful benefit”.
Professor Jonathan Schott of the UK Dementia Research Institute at UCL echoed this, stating that by “combining studies of different drugs, many of which have long since been disbanded… it is almost inevitable that the conclusion will be that as a group they are clinically ineffective.”
Charities also contest the definition of “clinically meaningful”. Dr Susan Kohlhaas, executive director of research at Alzheimer’s Research UK, argued there is no universally agreed definition and that current trial measures may not capture what matters to families. She highlighted that families often report that “even a delay of several months in decline could provide valuable, meaningful time” with loved ones.
Alzheimer’s Research UK further stated that the review relies heavily on evidence from older, discontinued drugs, “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”. Professor Richard defended the methodology, noting all the drugs share the same amyloid target and that the results were consistent even when studies were viewed separately.
Nice’s ongoing re-evaluation
The debate unfolds as the National Institute for Health and Care Excellence (Nice) is re-evaluating lecanemab and donanemab for use on the NHS. Both drugs were previously rejected, with Nice deeming their benefits “too small” to justify the cost—a decision upheld as recently as June 2025.
However, following successful appeals by the manufacturers Eli Lilly and Eisai, Nice has agreed to a reconsideration. The appeals centred on claims that Nice failed to adequately account for the quality of life of unpaid carers and did not give manufacturers enough time to respond to NHS England’s estimates for the cost of administering the intravenous infusions.
The reassessment will also factor in new, higher cost-effectiveness thresholds introduced as part of a UK-US trade deal. The consultation period for this fresh appraisal closes on 28 April 2026, with the committee scheduled to meet again on 10 June 2026.
This reconsideration happens against a backdrop of significant economic pressure, with informal dementia care estimated to cost the UK economy over £20 billion annually, and a perception that the UK is falling behind other countries where patients are already accessing these treatments.
