Alzheimer’s ‘wonder drugs’: from hope to hype to a sobering reality

Paul comes to see you with his 75 year old wife Betty. Betty has early Alzheimer’s Disease, and Paul is doing a wonderful job as her carer. He has read about the new “wonder drugs” and asks, quite reasonably, whether Betty can have one. She could have years of good quality life left, so how could the NHS deny her that chance?

Over the last few years we have had plenty of excited headlines about the new monoclonal antibodies for Alzheimer’s disease (AD), hopes and expectations have been raised and we have all had to have difficult consultations with the like of Paul and Betty. This started back in 2022 when lecanemab was the lead story on the BBC News, ‘hailed as a momentous breakthrough’ heralding a ‘new era of drugs to treat AD’. This hope of a genuine breakthrough was followed by plenty of media hype: a succession of positive media stories about these drugs which greatly raised hopes and expectations. Then last week there was a sudden shift in tone with the BBC reporting that these drugs are now ‘unlikely to benefit patients’, the previously very excited Daily Mail saying that they ‘do not work’ and other similarly negative headlines. These all followed the publication last week of a new Cochrane systematic review Cochrane 2026, CD016297.

So, how did we get here? 

The rationale behind these drugs is compelling. In early Alzheimer’s disease, beta-amyloid proteins accumulate in the brain. These are neurotoxic, detectable before symptoms develop and have long been thought to play a central role in pathogenesis. Drugs such as lecanemab and donanemab are monoclonal antibodies designed to bind to amyloid and trigger its clearance via the immune system. Early trials, such as the Clarity AD Trial for lecanemab and the TRAILBLAZER-ALZ Trial for donanemab showed promising results, the drugs clearing the beta-amyloid from the brain and with some evidence of slowed clinical progression. For a condition with no real disease-modifying options, this was indeed exciting stuff. However, already in 2023 a BMJ editorial questioned how clinically relevant the results were, highlighted the risks of cerebral oedema and bleeds and advised that much more research and longer term follow up was needed before we could understand where the true risk/benefit equation lay. The drugs were both licensed in the UK by the MHRA, but not approved for NHS use by NICE on the basis of cost-effectiveness (a decision currently under an appeal BMJ 2026) and some patients have been accessing them privately at huge personal cost.

And where are we now? The new Cochrane review Cochrane 2026, CD016297

Last week’s Cochrane review has now completely changed the mood music around these drugs.The review included 17 placebo controlled randomised trials with around 20,000 patients with mild cognitive impairment or Alzheimer’s dementia, assessing seven different beta-amyloid targeting monoclonal antibodies. The average age was relatively young at 70 to 74.

After 18 months, the now sobering reality is that they found ‘convincing evidence of the absence of a clinically meaningful effect’. The effect on cognitive function and dementia severity was described as ‘absent or trivial’ with ‘little or no difference in functional ability’. There was a small increase in cerebral oedema and microbleeds, but the long-term implications of these imaging findings remain uncertain. There was fortunately no increase in mortality or serious adverse events. The authors conclude that ‘the current results make clear that successfully removing amyloid from the brain probably does not result in a clinically meaningful effect on cognitive function’ and that future research on potential therapies should focus on new mechanisms of action rather than amyloid removal. 

As with any systematic review, there are limitations. The included studies were heterogeneous, seven different drugs were analysed together and maybe more time is needed to see clinically significant results. However, the authors state that the review was conducted using rigorous Cochrane methodology and represents the most comprehensive synthesis of the evidence to date BMJ2026;393:s719.

So, what are the implications for primary care?

Firstly, this is deeply disappointing for Betty and Paul and thousands of other patients and families who will have followed the earlier headlines and invested real hope in these treatments. Acknowledging that emotional impact is important. For us, these are not abstract scientific debates but are personal, often difficult conversations which impact patient’s lives.

Secondly, it reinforces the importance of clear, honest communication about clinical evidence. We need to explain that while the science is impressive and the drugs do what they are designed to do at a biological level, this has not translated into meaningful clinical benefit. That distinction is crucial and poorly conveyed in media reporting.

Thirdly, it brings the focus back to what we can do. Optimising comorbidity, reviewing medication to reduce anticholinergic burden, supporting carers and addressing lifestyle factors remain central to good dementia care. Risk reduction and holistic management make a difference and are the core of our current approach.

There is also a broader lesson here about the importance of evidence-based medicine, with two of its best-known principles being well illustrated. The first is not to confuse statistical significance with clinical significance. Small changes in cognitive scores may reach statistical thresholds but be imperceptible to patients. The second is a reminder to always be wary of surrogate markers. Improving a biomarker or a scan does not necessarily mean patients will feel, function or live any better.

In conclusion, the results of the Cochrane review may be disappointing but this is typical of science where progression of knowledge is never linear. The amyloid hypothesis has driven decades of important research which will yield other benefits, such as the emerging Alzheimer’s disease bio-markers and other potential new therapies. But for now, they remind us that hope, while essential, must always be grounded in evidence which is clinically meaningful to patients like Betty.