Drugs once hailed as the beginning of the end for Alzheimer's disease "make no meaningful difference" to patients, a bombshell review has concluded. A team of international experts found that medicines targeting the toxic amyloid protein have a "trivial" effect on cognitive function and dementia. The expensive therapies can also cause rare but serious side effects including brain swelling and bleeding.

However, the review's methods have been strongly criticised by Alzheimer's charities and some researchers. They argued that the analysis diluted the benefits of the two most successful drugs - lecanemab and donanemab - by pooling their results with other failed ones. Writing for the Express, Professor Rob Howard, a leading critic of the drugs, and Professor Sir John Hardy, the geneticist who pioneered the theory that amyloid accumulation drives Alzheimer's in the 1990s, set out their opposing views.

Prof Howard, an expert in old age psychiatry at UCL, said the findings were "unsurprising". He added: "Hopefully this will help to correct some of the hype and the unrealistic expectations that have been raised about the drugs.

"We should definitely be more realistic because it's cruel to patients and families to raise false hope. It's a kind of misinformation, but it's also a mistake to think that Alzheimer's disease is something that we can easily crack in a few years' time.

"It's more difficult than establishing a colony on Mars. It's something that we will do one day, but it's not going to happen in the next five or 10 years."

Sir John, who is vice president of Alzheimer's Research UK, said the review was "misguided" because it "conflates different therapies with different mechanisms".

He said: "Lecanemab and donanemab have shown us that slowing Alzheimer's is possible, representing genuine progress. They are not perfect, but they have opened the door to a new era of treatment.

"Antiamyloid drugs were the first step; the next wave of treatments has the potential to go much further."

Lecanemab and donanemab were widely celebrated as breakthrough medicines when clinical trial results were unveiled in 2022 and 2023. They were the first drugs proven to both clear amyloid from patients' brains and slow symptoms.

But some doctors warned that the changes measured in the studies were too small to be noticed by patients and their loved ones.

Both drugs were rejected in 2024 by the NHS spending watchdog, NICE, after a committee decided the benefits were "too small to justify the costs". The annual price of the drugs and administering treatment has been estimated at £50,000-£80,000 per person.

London-based global organisation Cochrane brings together leading experts to analyse high-quality evidence on a particular topic.

Its reviews are widely recognised as the gold standard of evidence-based medicine and can influence decisions about which drugs should be offered on the NHS.

Cochrane's analysis of anti-amyloid drugs for dementia included evidence from 17 clinical trials of nine medicines, all of which targeted the same protein in slightly different ways.

The data covered 20,342 participants with an average age of 70-74. Most had either mild cognitive impairment, which causes problems with thinking and memory, dementia, or both.

The review team also worked with clinicians and dementia carers to set thresholds for what size of effect might be meaningful to a patient.

Cochrane's report concluded that the drugs' effects on cognitive function and dementia severity after 18 months of treatment were "trivial", while the effect on functional ability was "small at best".

Co-author Professor Edo Richard, a professor in neurology at Radboud University Medical Centre in the Netherlands, said the differences were "far below the minimal effect that's needed to be noticeable at all for patients and caregivers".

Dr 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."

Asked about the decision to include failed drugs that have been abandoned in the review, Dr Nonino said the results remained the same when those older studies were excluded, and in individual analyses of lecanemab and donanemab.

He added: "It is common for trials to find statistically significant results that do not translate into a meaningful clinical difference for patients."

The review also found that the drugs increased the risk of brain swelling and bleeds, known as ARIA, which were not always reported transparently in the trials.

Amyloid has been the focus of billions of pounds' worth of research in recent decades.

The review suggested that attention should be turned to other possible drug targets. Dr Richard added that although the drugs could successfully remove amyloid, "this does not correlate with any effect on cognition".

He said: "There's nothing more that I would like as a doctor than to finally be able to prescribe a drug that provides a bit more hope to patients and their families, but I'm always wary to avoid giving people false hope."

Commenting on the report, Professor Paul Morgan, director of the UK DRI Cardiff, Cardiff University, said: "The findings, while not unexpected by many observers in the field, will likely generate vigorous debate in what has become a key controversy.

"They support the growing view that removal of amyloid is not, alone, sufficient to significantly improve cognition or slow disease progression when administered early in the disease course."

Professor Bart De Strooper, group leader at the UK Dementia Research Institute at UCL, said the review was "problematic" because it pooled data from both trials of drugs that failed and those that had positive effects.

He said: "Once failed and successful programmes are combined into a single pooled estimate, the average will inevitably look weaker than the best-performing agents."

Dr Susan Kohlhaas, executive director of research at Alzheimer's Research UK, said the review attempted to "paint an entire class of drugs with the same brush even though we know different anti-amyloid treatments can act in different ways".

Dr Richard Oakley, associate director of research and innovation at Alzheimer's Society, said the inclusion of results for a large number of failed drug trials and a small number of more recent, successful ones "make the picture look bleaker than it really is".

He added: "It's essential that we interpret this review with nuance and avoid taking a sledgehammer to decades of pioneering scientific study."

Professor Paresh Malhotra, head of division of neurology at Imperial College London, said: "I agree with the authors that other mechanisms of action beyond targeting amyloid for treatment of Alzheimer's should be explored.

"However, the findings to-date do not justify 'throwing the baby out with the bathwater' and dismissing all the results of well-conducted individual studies.

"The results of ongoing amyloid-targeting trials will help us understand these treatments better, and we should continue to explore all promising avenues for the treatment of Alzheimer's and other dementia-causing diseases."

Cochrane Reviews are quite prestigious. They carry weight and they are seen as being very independent. Hopefully this will help to correct some of the hype and the unrealistic expectations that have been raised about the drugs.

There are people whose careers are invested in demonstrating that amyloid is really important and treatment based on removing it is going to change the lives of patients, because it's their life's work.

While disappointing, the results and conclusions should not come as a surprise to those who have appreciated the very small benefits of treatment seen in the individual clinical trials of these drugs.

While these benefits may have achieved statistical significance when data from very large numbers of participants allowed the detection of tiny differences, they did not achieve accepted levels of clinical efficacy or what would be appreciable in an individual patient.

My dad had Alzheimer's disease about 20 years ago. If he was ill now, I would not want him to have these treatments because the benefits are just too tiny to notice and there are risks.

He and my mum would also have been gummed up with infusions every couple of weeks, having extra MRI scans and worrying every time he got a headache - was that because he was getting an ARIA event [brain bleeding or swelling]?

This may be disappointing news but we should not be discouraged.

Alzheimer's disease is a difficult condition to try and treat and reverse. One day we'll have treatments, but it might not be for 50 or 100 years.

We have to look at cracking Alzheimer's disease in that sort of perspective. Nothing is wasted, we're learning more about what happens and more about the brain.

Compared with when I started in this area 30 or 40 years ago, our understanding is much more sophisticated. We'll get there, it's just not going to be in the next five years.

- Prof Rob Howard is a professor of old age psychiatry at UCL

Debate about the value of antiamyloid drugs has been ongoing for many years and will continue as new evidence emerges.

But the latest Cochrane review dismissing these drugs is misguided because it pools data from drugs that had different mechanisms, which is simply wrong.

Especially since two of these - lecanemab and donanemab - have shown benefit and have been licensed for use by regulators across the globe.

Lecanemab and donanemab have shown us that slowing Alzheimer's 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 the field is moving rapidly, and the pipeline of potential therapies is more diverse and promising than at any point in my career.

Researchers are now looking a diverse array of drugs that target a myriad of biological processes involved in Alzheimer's.

Some of these are repurposed existing medicines, which have already been shown to be safe for use in people. This could potentially speed up the process of testing them in Alzheimer's trials, reducing development costs.

This breadth of research is crucial, as Alzheimer's is a complex disease, and the future of treatment will not be a single approach but a combination that tackles different aspects of the condition.

But the NHS is not ready for the new dementia treatments that research will soon deliver. It must prepare by running pilot studies to understand how to best implement newly licensed treatments.

These studies would give some people access to new treatments and help the NHS learn what the system needs to safely deliver them.

Antiamyloid drugs were the first step; the next wave of treatments has the potential to go much further.

For the first time, I can see a future where Alzheimer's is treated with the same confidence and combinationbased approach we use for other major diseases, like cancer.

That gives me real hope, but we'll only get there through research.

- Prof Sir John Hardy works at the UCL Institute of Neurology and is vice president of Alzheimer's Research UK