A storm has erupted after a recent Cochrane review suggested that drugs intended to slow Alzheimer’s disease progression “make no meaningful difference to patients” and actually increase the risk of brain swelling and bleeding, reports The Independent.
Charities have accused the experts behind the findings of unfairly combining failed and successful drug trials.
In their review, the researchers wrote that the effects of these medicines on people with early-stage Alzheimer’s and dementia were “either absent or consistently small”.
Edo Richard, a Professor of Neurology at Radboud University Medical Centre in The Netherlands, noted his team observed “results from trials over the past two decades are not consistent”.
Charities argue that the review’s authors have attempted to “paint an entire class of drugs with the same brush”, potentially undermining the benefits of certain treatments.
Anti-amyloid medicines work by binding to and clearing protein deposits in the brains of those with Alzheimer’s, a process intended to slow cognitive decline.
Two anti-amyloid drugs – lecanemab and donanemab – are licensed for use in the UK.
The treatments were not approved for use on the NHS after the National Institute for Health and Care Excellence (NICE) deemed their benefits “too small” to justify the cost.
The Cochrane review looked at 17 studies involving 20 342 patients overall.
Most had either mild cognitive impairment (MCI), which causes problems with thinking and memory, dementia, or both, with a mean age of 70 to 74.
The studies included trials on lecanemab and donanemab, as well as aducanumab, which has been discontinued by its manufacturer, and bapineuzumab, crenezumab and solanezumab, which were discontinued after failed trials.
The analysis found that the effects of these drugs on cognitive function and dementia severity after 18 months was “trivial”.
According to Richard, the differences made by the treatments were “far below the minimal effect that’s needed to be noticeable at all for patients and caregivers”.
Francesco Nonino, neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna in Italy, said: “Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients.
“There is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect.
“While early trials showed results that were statistically significant, it is important to distinguish between this and clinical relevance. It is common for trials to find statistically significant results that do not translate into a meaningful clinical difference for patients.”
The drugs could also increase the risk of swelling and bleeding in the brain, according to the study.
These side effects were seen in brain scans and caused no symptoms for most patients, although the long-term impact was unclear.
Nonino also highlighted that most studies reported after 18 months, which he described as a “relatively short” window “in the context of a slowly progressive condition like Alzheimer’s”.
“Also, it has to be remembered that these drugs in clinical practice may likely be used for much more than 18 months,” he said.
Richard, who runs a dementia clinic, said he was honest with patients about the effect of the approved drugs and that they were “too small for patients and caregivers to notice”.
He said he also highlighted potential side effects, the need for various scans and tests to confirm eligibility, and that patients would need to visit the clinic every two to four weeks to have the treatment from an IV drip.
He added: “I would tell them… I think you will probably not benefit from these drugs, and they’re burdensome for you and your family.
“I just think it’s extremely important that we’re honest to our patients about what they can expect… there’s nothing more that I would like as a doctor to finally be able to prescribe them a drug which provides a bit more hope …but I’m always wary to avoid giving false hope.”
Reacting to the findings, Dr 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 Alzheimer’s.
“It’s essential that we interpret this review with nuance and avoid taking a sledgehammer to decades of pioneering scientific study.”
Jonathan Schott, Professor of Neurology and group leader of the UK Dementia Research Institute at UCL, said: “By combining studies of different drugs, many of which have long since been disbanded, several of which had little or no effects on beta-amyloid, and most of which have failed in randomised clinical trials, it is almost inevitable the conclusion will be that as a group they are clinically ineffective.”
Dr Susan Kohlhaas, executive director of research at Alzheimer’s Research UK, said the charity regularly heard from families affected by dementia who said that even a delay of several months in their loved one’s decline “could provide valuable, meaningful time” that “shouldn’t be minimised”.
She said: “Crucially, this study 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.
“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.
“But it’s not accurate to dismiss their impact as ‘trivial’, especially when the analysis has clear constraints that limit what it can tell us.”
The review comes after it emerged NICE is looking again at evidence on donanemab and lecanemab after successful appeals by their manufacturers Eli Lilly and Eisai.
Study details
Amyloid‐beta‐targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer’s disease
Francesco Nonino, Silvia Minozzi, Luisa Sambati et al.
Published in Cochrane Library on 16 April 2026
Abstract
Rationale
Alzheimer’s disease is a neurodegenerative disorder and the most common cause of dementia. Aggregated amyloid‐beta protein deposits are implicated in its pathogenesis. Amyloid‐beta‐targeting monoclonal antibodies (sometimes represented as Aβ‐mAbs) are potentially disease‐modifying for Alzheimer’s disease: through the clearance of amyloid in the brain, they may slow cognitive and functional decline.
Objectives
To assess the clinical benefits and harms of amyloid‐beta‐targeting monoclonal antibodies aducanumab, bapineuzumab, crenezumab, donanemab, gantenerumab, lecanemab, ponezumab, remternetug, and solanezumab in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease.
Search methods
We searched CENTRAL, MEDLINE (PubMed), Embase, and two clinical trials registries (Clinicaltrials.gov and WHO International Clinical Trials Registry Platform), and we undertook reference checking and citation research. The most recent search date was 7 August 2025.
Eligibility criteria
We included randomised controlled trials (RCTs) that lasted at least 12 months and compared amyloid‐beta‐targeting monoclonal antibodies with placebo or no treatment in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease. We included both parallel‐group and cluster designs.
Outcomes
Our outcomes of critical importance were: cognitive function; dementia severity; functional ability; any amyloid‐related imaging abnormality (ARIA), which includes oedema (E) and haemorrhage (H); any symptomatic ARIA E and H; symptomatic brain haemorrhage; serious adverse events; and any‐cause mortality. We analysed data at 12, 18, 24, and over 24 months of treatment.
Risk of bias
We used the Cochrane risk of bias tool RoB 2 to assess the risk of bias in outcomes of critical importance.
Synthesis methods
We meta‐analysed results for each outcome within each comparison using the inverse variance method and the random‐effects model. We used GRADE to assess the certainty of evidence for each outcome as very low, low, moderate, or high.
Included studies
Overall, we included 17 studies with 20,342 participants. The mean age of participants in the studies ranged from 70 to 74 years. Seven studies enroled only participants with mild dementia, and one study enrolled only participants with mild cognitive impairment. The remaining studies included a mixed population. The mean duration of participants' cognitive impairment ranged from 17 to 52 months.
The 17 studies assessed seven different amyloid‐beta‐targeting monoclonal antibodies: aducanumab (n = 3), bapineuzumab (n = 4), crenezumab (n = 2), donanemab (n = 1), gantenerumab (n = 4), lecanemab (n = 1), and solanezumab (n = 2). All used placebo as a comparison. Eleven studies lasted 18 months, four lasted 24 months, and two lasted more than 24 months.
All studies were funded by the pharmaceutical industry.
Synthesis of results
Below, we report the results of the studies at 18 months.
Cognitive function
Compared to placebo, amyloid‐beta‐targeting monoclonal antibodies probably result in little to no difference in cognitive function as measured by the ADAS‐Cog (Alzheimer's Disease Assessment Scale‐Cognitive) scale (standardised mean difference (SMD) −0.11, 95% confidence interval (CI) −0.16 to −0.06; 13 studies, 9895 participants; moderate certainty).
Dementia severity
Amyloid‐beta‐targeting monoclonal antibodies may result in little to no difference in dementia severity as measured by the CDR‐SB (Clincal Dementia Rating Sum of Boxes) scale (SMD −0.12, 95% CI −0.24 to −0.00; 9 studies, 8053 participants; low certainty).
Functional ability
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 (SMD 0.09, 95% CI 0.03 to 0.16; 3 studies, 3478 participants; moderate certainty) and may result in a small increase in functional ability if measured with the ADCS‐iADL (Alzheimer's Disease Cooperative Study‐Instrumental Activities of Daily Living) scale (SMD 0.21, 95% CI 0.10 to 0.32; 1 study, 1252 participants; low certainty) or ADCS‐ADL‐MCI (Alzheimer's Disease Cooperative Study ‐ Activities of Daily Living for Mild Cognitive Impairment) scale (SMD 0.23, 95% CI 0.12 to 0.33; 4 studies, 2802 participants; low certainty).
Adverse events
Amyloid‐beta‐targeting monoclonal antibodies probably result in a small increase in the occurrence of any ARIA E (ARD (absolute risk difference) 107 more per 1000, 95% CI 77 more to 148 more; 11 studies, 13,595 participants; moderate certainty) and probably little to no difference in symptomatic ARIA E (ARD 29 more per 1000, 95% CI 22 more to 38 more; 2 studies, 3522 participants; moderate certainty) or symptomatic ARIA H (ARD 4 more per 1000, 95% CI 1 fewer to 31 more; 1 study, 1795 participants; moderate certainty).
Three studies assessing any ARIA H showed heterogeneous results (I2 = 81%), which prevented pooled analysis.
At 18 months, amyloid‐beta‐targeting monoclonal antibodies do not increase serious adverse events (ARD 6 more events per 1000, 95% CI 10 fewer to 26 more; 9 studies, 11,904 participants; high certainty) or overall mortality (ARD 2 more events per 1000, 95% CI 3 fewer to 11 more; 7 studies, 9733 participants; high certainty).
We judged the overall risk of bias as low for the outcomes of serious adverse events and mortality. We had some concerns about the overall risk of bias for efficacy outcomes, mainly due to the risk of functional unblinding (i.e. participants and investigators correctly guessing whether a participant is receiving the active drug or placebo because of noticeable side effects).
Authors' conclusions
The effect of amyloid‐beta‐targeting monoclonal antibodies on cognitive function and dementia severity at 18 months in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease is trivial, while on functional ability, it is small at best. Amyloid‐beta‐targeting monoclonal antibodies increase the risk of amyloid‐related imaging abnormalities. Both desirable outcomes and adverse events were inconsistently reported in the studies included in the review.
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 Alzheimer’s disease. Future research on disease‐modifying treatments for Alzheimer’s disease should focus on other mechanisms of action.
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