A commentary in response to the recent Cochrane review of clinical trial data on different anti-amyloid treatments, that states these medicines show ‘no clinically meaningful benefit’ for people with Alzheimer’s.
Guided by our Medical & Scientific Advisory Panel (MSAP), Alzheimer’s Disease International’s position is that people making decisions about treatment benefit from information that is specific, balanced, and transparent. This includes an honest discussion of the potential advantages, the limitations, and the uncertainties of each approved therapy. Approaches that combine results from multiple drugs with very different characteristics can unintentionally obscure both signs of benefit and risks, precisely at a time when people affected by MCI (Mild Cognitive Impairment) or by dementia due to Alzheimer’s disease and carers are seeking practical guidance.
The recent Cochrane review concluded that amyloid-targeting monoclonal antibodies show little or no clinically meaningful benefit overall and a small increase amyloid-related imaging abnormalities (ARIA), such as brain swelling and microbleeds. While methodologically rigorous in many respects, the review raises important questions about whether such pooling best serves people trying to understand today’s treatment options.
The debate is not simply about whether anti-amyloid drugs “work” or “do not work,” but whether the review’s pooled methodology blurred important differences between older unsuccessful drugs and the two approved antibodies, lecanemab and donanemab.
From the perspective of Alzheimer’s Disease International, the central concern is not that benefit-risk questions should be avoided. They should not. People affected by MCI or by dementia due to Alzheimer’s disease and families deserve open discussion about benefits, side effects, monitoring burden, and uncertainty. The concern is that pooling very different drugs targeted different species of beta amyloid from very different stages of scientific development into one average estimate can distort the picture, especially for non-specialists trying to make sense of what this means for the treatments actually available today. That concern has been raised repeatedly by dementia research and advocacy voices responding to the review, including the Alzheimer’s Society, Alzheimer’s Research UK, and other academic researchers.
This matters because anti-amyloid antibodies are not a single uniform group of medicines. The Cochrane review itself covered seven different drugs. Some were unsuccessful. Some were discontinued. Some did not meaningfully remove amyloid. By contrast, newer agents such as lecanemab and donanemab have shown both a biological effect — reducing amyloid burden — and modest slowing of clinical decline in large trials. Combining these newer agents with many older unsuccessful studies makes the overall picture appear bleaker than the evidence on the currently approved drugs alone.
The same problem applies to safety. ARIA is a genuine and important concern, and nobody should minimise it. But safety should also be described precisely. When studies of drugs with little or no amyloid effect are pooled together with drugs known to cause higher ARIA rates, both efficacy and adverse events can be diluted or blurred, making the pooled figure less informative for real-world decision making. In other words, the answer people living with dementia need is not “all anti-amyloid drugs are the same,” but “what are the likely benefits and risks of this specific drug, for this specific person, with this specific care pathway?”
This is especially important because treatment decisions in early Alzheimer’s disease are already difficult. People affected by MCI or by dementia are being asked to consider therapies that may offer modest clinical benefit, come with monitoring requirements and safety concerns, and may not be suitable for everyone. Reviews that flatten crucial differences into a single class-wide verdict risk clouding, rather than supporting, those decisions.
It is also important to underline that regulators have reviewed these drugs individually rather than as a blurred group average. The fact these drugs have gained approval in multiple countries and jurisdictions reflects that they are efficacious, even while debate continues about their overall value, cost-effectiveness, and system readiness.
For Alzheimer’s Disease International, the message to patients and families must therefore hold two truths at the same time. First, these treatments are not positioned as cures, they are early-stage breakthrough treatments , and the risks and benefits require careful individual consideration. Second, it is misleading to imply—based on pooled analyses alone—that the therapies now available have no meaningful place in care or future research. The more constructive question is how to determine which treatments help which people, under what circumstances, and with what safeguards in place. Treatment decisions must remain personalised.
Ultimately, ADI believes that the review’s conclusions are overly pessimistic and do not fully reflect the potential of new anti-amyloid treatments.
On the review, Bill Yeates, ADI Board Member and Co-Chair of the Global Dementia Experts Panel said:
How can information like this (as presented in this paper) be explained clearly to people living with dementia? In saying this, I believe it is important to be careful not to convey the message that there is nothing that can be done—there needs to be a ray of hope. It is still possible to live an enjoyable and meaningful life through access to person-centred care, the use of reablement approaches, and the implementation of lifestyle changes alongside a range of psychosocial interventions focused on improving quality of life.
ADI Medical & Scientific Advisory Panel comments
Miia Kivipelto, Chair of the Medical & Scientific Advisory Panel
“The recent Cochrane review on anti-amyloid therapies for Alzheimer’s disease has generated significant discussion worldwide. After more than two decades without new treatments for Alzheimer’s disease, two anti-amyloid therapies—lecanemab and donanemab—have now been approved in several countries. However, the review concludes that removing amyloid from the brain may not lead to clearly meaningful clinical improvements for people with mild cognitive impairment or early Alzheimer’s disease.
The Cochrane review aggregated data from 17 randomized trials of multiple amyloid immunotherapy agents involving more than 20,000 participants, concluding that these therapies likely result in little to no difference in cognitive function or dementia severity, alongside small increases in adverse events.
It is important to interpret these conclusions with care because there are several methodological considerations. The review combines results from many different therapies, including some that did not effectively target or sufficiently remove amyloid. Pooling agents with differing mechanisms and levels of biological activity makes it more difficult to detect the true impact of the newer, more promising treatments.
Even modest slowing of disease progression can matter. Delaying decline may help people maintain independence for longer and postpone the need for more intensive care—outcomes that can be highly meaningful for individuals and families living with Alzheimer’s disease.
These therapies represent the first generation of disease-modifying treatments. While their effects are still limited, they mark important progress and provide a foundation for further advances in treatment and prevention.”
Louise Robinson, Co-Chair of the Medical & Scientific Advisory Panel
“Whilst I welcome such a detailed review on the new emerging treatments, I feel the results need to be interpreted with some nuance. Combining the results of older, less successful drug trials with newer ones, which show some early, more promising results, may lead to confusion for both professionals and the public.”
Serge Gauthier, Executive Committee Member of the Medical & Scientific Advisory Panel
“I thank ADI for its leadership in setting the record straight and giving persons living with MCI or with dementia due to Alzheimer’s disease access to more treatment options. It is also an opportunity to broaden the scope of interest and influence of ADI to the MCI stage of Alzheimer’s disease, with delaying onset of dementia as an important therapeutic target.”
Ricardo Allegri, Executive Committee Member of the Medical & Scientific Advisory Panel
“Scientific advances in the treatment of Alzheimer’s disease have a significant impact on society, and on individuals affected by the disease and their families. Unfortunately, the Cochrane review contains scientific biases that are difficult for the public to understand. The results of 22,342 patients who received treatment targeting cerebral amyloid protein were analyzed and it was concluded that there was either minimal or no clinical benefit. However, the review treats antibodies targeting different types of beta-amyloids as equivalent, despite some never progressing beyond the research stage due to a lack of positive results, while others, such as lecanemab and donanemab, demonstrating both biological and clinical changes and being approved by regulatory agencies. Anti-amyloid drugs in clinical use are indicated for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease. However, it is essential to fully understand the delay in disease progression that these drugs provide, as well as the adverse effects. This must be assessed for each individual patient at the appropriate time and under the right conditions. The Cochrane review introduces bias into the results, leading to an interpretation that further confuses the patients and their families. Although limited, these treatments represent promising first steps in disease-modifying therapy and mark a hopeful breakthrough in both research and clinical practice regarding Alzheimer’s disease”