So, how likely is that? Are we really on track to be one year away from a cure? Right now, dementia and Alzheimer’s disease are the leading cause of death in England and Wales, with the number of cases predicted to triple over the next 40 years. That means, if nothing changes, one in two of us will be directly affected by it — either by caring for someone with the condition, or developing it ourselves. Yet no new drug has been approved for Alzheimer’s in 20 years.

No wonder, then, that at the end of last year, the news that two new dementia drugs were set to be approved for use in Britain was greeted with great excitement. The drugs, lecanemab and donanemab, were both celebrated as a “new era” in Alzheimer’s treatment, claiming to slow the progression of disease. Until now, treatment has only slightly alleviated the symptoms, at best. Since the announcement, Alzheimer’s Research UK and the Alzheimer’s Society have renewed efforts to get them to patients.

Now, we are told that “routine screening for over-50s [is] closer”. Research published this week in JAMA Neurology linked blood test results of a protein implicated in Alzheimer’s disease, tau, to a later changes on scans. The clamour for the “wonder drugs” will inevitably grow louder. But can we believe the hype?

Dementia has long existed across human history. And Alzheimer’s is the most common form. While advances in medicine have increased our understanding of the disease, and we know that age, genetics and lifestyle play a part in the progression of it, we still don’t know what triggers it. Aluminium exposure is one theory; infection and immune system malfunctions have also been posited, though are treated as unproven. But the most enduring one, and the one into which most funding flows, is the “Amyloid Hypothesis”.

Amyloid protein is found in all healthy people but in Alzheimer’s disease, the protein is found to have behaved abnormally: it clumps together forming plaques which cause “tangles” which disrupt communication between the brain cells. The cells malfunction, die and, over time, different areas of the brain shrink. The “clumps” cause the production of another protein, tau, which causes tangles and more damage; the two have been called the “trigger and bullet” in the disease. 

The two new “wonder drugs” both address the amyloid theory. Both are “monoclonal antibodies”, which target the protein in different ways. Donanemab’s antibodies recognise and remove amyloid when it is in plaque form, while lecanemab targets the amyloid as it forms fibres and tangles. But they don’t come cheap. Lecanemab is priced at £21,000 per patient annually with donanemab expected to be similar. And this, along with their efficacy, will be what Nice is looking at before it decides to recommend the drug — or not — later this year.

The new drugs certainly seem credible. Large trials have been conducted and published in high-profile journals, examining their impact on memory, brain scans and blood test results.

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The Trailblazer study investigating donanemab was published in JAMA last year. It assessed over 1,700 adults, with an average age of 73, who had been diagnosed with early Alzheimer’s. Over 18 months, half of those studied received the active drug and half the placebo, all of them completing disease scores, indicating symptoms and cognitive ability as the trial progressed.

Eli Lilly, the drug developer, stated in a press release that “47% of participants on donanemab showed no decline on CDR-SB, a key measure of disease severity after 1 year, compared with 29% of participants on placebo.”  Moreover, “participants on donanemab had 40% less decline in ability to perform activities of daily living at 18 months”. Meanwhile, images of brain scans which seem to persuasively illustrate the disappearance of amyloid were widely published.

Given that dementia progresses over a period of time at differing speeds, the developers were keen to highlight their “rate of decline” measurement. The implication of their results was a significant slowing of the disease. But that by no means tells the whole story. Participants in the trial also had their cognitive function measured on the Alzheimer Disease Rating Scale. For those taking the placebo, their scores dropped by an average of 13 points. For those taking donanemab, their scores also dropped — but by an average of 10 points. So both groups found their cognitive function worsened, but with a difference of three points on a scale of 146. The question to ask must surely be: how much difference do those three points make.

As for the lecanemab trials, Biogen and Eisai announced “highly statistically significant results… representing a 27% slowing of decline”. These were conducted in a slightly different fashion. The 1,795 adults, ranging in age from 50-90, were assessed on an 18-point score in tests which looked at their memory, problem solving, hobbies and abilities in personal care. Half got the active drug, the other half, placebo.

After 18 months, both groups had experienced decline, as would be expected in people with dementia. Those taking lecanemab had scores which had declined by an average of 1.21 points. And those on the placebo had deteriorated more, by an average of 1.66 points over the course of the trial. That’s a difference of 0.45 points on an 18-point scale, described as “moderate” in the paper.

It is also important to note that the people who were recruited to the trials were only those with the “purest” forms of Alzheimer’s. For every 10 patients put forward, seven or eight were rejected. Those who were accepted had high amyloid levels but were relatively young and free of other diseases. To pick these patients, according to Dr Seb Walsh, a public-health doctor researching dementia at Cambridge University, is to misrepresent how the disease occurs among the vast majority of the population. Most people’s dementia is complex, occurring when they are in their eighties, and caused by several disease processes.

“By selecting amyloid-only patients,” he says, “they were giving the drug the best possible chance to show an effect, and yet even so they found an effect (after 18 months of fortnightly infusion treatment) that was so small it probably wouldn’t be noticeable to a doctor.” If the drug were given to a broader range of people diagnosed with Alzheimer’s disease, the already-small improvements might even disappear altogether.

And there’s another problem. The side effects.

Over a quarter of the participants in the lecanemab trial suffered drug infusion reactions, while there was brain swelling (which can be mild, such as flushing, or more severe, with changes in breathing and heart rate) in 13%. Others experienced headache, confusion and visual disturbance. Donanemab had similar side effects and three people also died in the trial — something researchers ascribed to the treatment.

So, while the press releases make a persuasive case for the effectiveness of the drugs, the overall difference is so small as to invite the question as to whether patients or families would even notice. What sort of improvement would these small differences represent in the real-world? And more important: are they worth the risk?

“My view,” says Professor Robert Howard, Professor of Old Age Psychiatry at University College London, “is that we’ve just about reached the point where we couldn’t have treatments that remove amyloid more aggressively because of the side effects of brain bleeds and swelling.”

It is this finding that is exercising — and dividing — scientists. For what does it mean for the new drugs if, as the trial showed, a big reduction in brain amyloid doesn’t translate into a hugely impressive reduction in or slowing down of symptoms.

One body of clinicians continues to hold to the hypothesis. Craig Ritchie, a Professor of the Psychiatry of Aging at the University of Edinburgh, worked on the donanemab trial and claims it has “a profound effect on the core pathology of Alzheimer’s disease namely cerebral amyloid”. He maintains that the slowing of the progression of the disease coupled with a reduction in amyloid build-up is not a coincidence. He believes that more time is needed to show the full impact of the reduction in amyloid on symptoms. “These drugs give us hope that we can do something, that these are the first drugs of an important new generation of treatments.” In order to push out this treatment, he has quit the NHS and set up Scottish Brain Sciences as an “independent research company” to run studies and give patients free access to the latest diagnostic tests and medications through trials funded by the drug industry. He, too, is funded by the industry.

These proponents of the new drugs also insist that monoclonal antibodies will show more impact if they are given before amyloid has damage to the brain. Therefore, they say, it needs to be given earlier — possibly even before someone has any symptoms of dementia.

That’s where the proposal that screening people — the so-called “Alzheimer’s blood test”  would come in. It would test people before they have any memory problems for their future dementia risk. But, offered as a “check up”, it would come with wide ethical issues. There would inevitably be false positives and negatives — causing needless anxiety or false reassurance. Nor would a result necessarily lead to people being offered treatments that could lower their chances of getting dementia later. But could it make sense in a research setting, as an opportunity to try these new treatments to see if they could make a difference if given earlier? 

Professor Howard is sceptical. The amyloid treatment, he says, “is a cul de sac, a dead end. And, worse, it means that the money and energy in drug development and trials isn’t being put into something that might work.” he says. “The argument that maybe the drugs need to be given earlier to make a difference is really just a wish or a hope. There is no data to suggest that it is true,” he says. “I worry that the “treat earlier” argument has become a way of saying ‘don’t blame the drugs for not working, blame the patients’.”

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Various Alzheimer’s charities have heavily advocated for these drugs to be made available quickly. When lecanemab was approved in the US, a public letter hosted by the US Alzheimer’s Association in 2023 described it as “a foundational gamechanger”, saying: “No barrier can be allowed to stand between our patients and a treatment that has a reasonable risk-benefit ratio.” There may be a less philanthropic reason why they are so enthusiastic about the new treatments. A closer look at the signatories revealed that some had drug industry connections. And the charity itself received over $750,000 from Eisai and $430,000 from Biogen in 2023, who make lecanemab.

The inevitable result of these two amyloid-removing drugs being licensed means all drug companies will want to make and market their own versions, regardless of the criticisms. After all, it’s harder for regulators to say “no” when there are similar drugs on the market and the big charities are rooting for them.

But that hasn’t stopped the charities from investing £5 million in developing a blood test that will “revolutionise dementia diagnosis”. They say that currently only 2% of people get the detailed diagnosis they need and that significant investment is needed to ensure the NHS can identify people with Alzheimer’s disease far sooner. The Blood Biomarker Challenge, available within five years, will help do that. “If we can fix diagnosis, we open the door for a cure. It’s a bold ambition but, with someone developing dementia every three minutes in the UK, we must aim high,” they say.

But Dr Seb Walsh, a public health doctor researching dementia at the University of Cambridge, says the hype and hope is unkind: “For 20 years we have been promised wonder drugs within 5 years — but still we wait,” he says.

He also says it’s bad research practice to pre-empt your results before you do the research. “We don’t know how useful these tests will be, how well they’ll perform in the ‘typical’ NHS dementia patient (more complex than the people in existing research studies), that’s the whole point of doing the research.”

But the key question, and the one that Nice will be weighing up over the course of the year, is whether any of these new drugs represent the best use of public money. Given the small benefits, the risk of side effects, but the lack of other decent alternatives, the question will be how to weigh that up as independently as possible. Spending similar sums on social care might well provide greater benefits for patients and families than the drugs. Is it right that a drug — with minimal benefits — should be funded when the same money invested into social care might do more good for patients and families getting more practical help?

Obviously, a drug that worked would have massive, global market potential. But the hyperbole from doctors and researchers in this area — especially those with industry funding — is unhelpful. It means that the pressure to upsell the effectiveness of a drug is particularly intense. This, then, diverts money into look-alike drug development and drains it from continued research. Clearly the pharmaceutical industry and its relationship with the private and public sectors has a lot to answer for. Currently, Alzheimer’s has no cure and treatment has progressed little despite decades of research and billions of pounds. As our investigation shows, we should be cautious about the promise of these new “wonder” drugs which risk benefiting only the drugs companies.

“There is still much we don’t know, but we really need to know,” Dr Walsh says. “We are unlikely to ever, truly ‘cure’ dementia — this is more false hope.”

The centre runs a protocol which claims patients can expect to see results within six months. And, according to its website, “to maintain improvements and prevent further cognitive decline, participants should consider the program as a long-term prospect”. This miracle treatment — the Bredesen Protocol — doesn’t come cheap. Patients are charged almost £3,000 for their first three appointments with any additional consultations costing another £475.

But with questions hanging over the effectiveness and harms of the two new Alzheimer’s wonder drugs, lecanemab and donanemab, expected to arrive on the market soon, any treatment that claims to reverse cognitive decline would be worth paying over the odds for. And right now, people are queuing up to pay. There are 21 practitioners and centres across the UK offering the Bredesen Protocol — or treatment plans based on his approach — charging anywhere up to £6,000 for consultations. Two say they are at “capacity”: suffering patients and their families are desperate to find something that might help their loved ones.

Desperation feeds exploitation and the Bredesen Protocol has been described by some scientists as quackery. The Alzheimer’s Society UK told us the regime was “not supported by scientific evidence”, while in Canada it is described as “offering ‘false hope”; and across various medical journals, academics suggest its use and promotion is ethically questionable.

Dr Dale Bredesen, however, claims that Alzheimer’s is “literally becoming optional”. A professor of molecular and medical pharmacology at UCLA, he has identified the 36 multifactorial “contributors” to the disease, and targets them “with a precision medicine type of approach”. This involves regular brain-training exercises, stress reduction plans and a ketogenic diet.

Deborah was diagnosed with Mild Cognitive Impairment aged 49 and told she was likely to develop Alzheimer’s. She had been having difficulty recognising people’s faces and switching words for a few years. After her sister-in-law discovered Dr Bredesen’s protocol, she signed up and was prescribed a plant-based diet, with virtually no red meat and plenty of intense exercise which she does on her Peloton bike. “All of a sudden, my brain started to work clearly. It was like the light went back on,” she says.

But mild cognitive impairment — MCI — is not the same as dementia. It refers to memory glitches which may be noticeable but don’t affect the person’s ability to function. Alzheimer’s Research UK says that about one in 10 people who have been diagnosed with mild cognitive impairment develop dementia each year. However, they also say that five in 10 will either stay the same or get better, with their memory returning to normal. Memory problems can be triggered by all manner of things: depression and anxiety, vitamin deficiencies, thyroid disorders — even some types of medication and being generally unwell, for example with a chest infection. Nonetheless, stories such as Deborah’s have been used as the basis of the evidence that the Bredesen Protocol works.

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Another is Bredesen’s “Patient Zero”. She was so depressed about her symptoms and prognosis that she had been saving up prescription pills to end her life. “I was so desperate at that point,” she says, “that I just wanted to check out.” She contacted Bredesen anonymously because she was afraid of losing her security clearance in her job. And after three months on the protocol, she noticed a transformative change. “I was just running around the house saying ‘I got my brain back I got my brain back.’ I was just so overjoyed,” she says. Convinced this proved the protocol worked, Bredesen reported her as a case study in a paper published in 2014.

When we wrote to Dr Bredesen saying his protocol had been described as “quackery”, he sent us this case report along with other research papers that he claimed provided the evidence for his treatment plan. He highlighted his medical qualifications obtained from some of the most prestigious establishments, that he’d worked in famous Nobel Prize-winning labs and had more than 230 peer-reviewed publications. “Few clinicians, and no reporters, understand the fundamental science that underpins what we are doing,” he says. “I doubt if any has read all of our publications.”

But according to Rob Howard, professor of Old Age Psychiatry at UCL, Bresenden’s claims are largely based on poor science that no reasonable practitioner would consider indicates efficacy. “He doesn’t really have any data that’s worth debating with him,” he says.

Indeed, the research that Dr Bredesen produced for us highlights problems with the way this sort of material is published and disseminated. He sent links to three studies, which he had previously referred to as “anecdotal reports” — the least reliable form of evidence. Another paper referred to the “trial” that clinics point to when they claim: “84% of the patients showed improvement.” But in fact the paper, published in the Journal of Alzheimer’s Disease, does not prove the protocol works. The 25 patients studied had a mixture of “dementia or mild cognitive impairment”, and given that many patients with MCI improve by themselves, we would expect to see improvements over time, regardless of treatment.

In any case, because the protocol uses multiple interventions, even if we did see genuine improvements, we would not know whether it was the simple advice that “worked” (prioritise sleep; eat a plant-rich diet; exercise for 45 minutes six days a week) — or if it was the complex regime of herbal supplements, “brain training”, “gut healing nutrients and digestive enzyme support” along with, for some patients, naltrexone (a drug used to treat opioid addiction and alcohol dependance). Bredesen’s conclusion that “it is possible to reverse cognitive decline in MCI and early dementia with a personalised, precision medicine” is astonishing, given that the nature of their study design meant they could prove no such thing.

Meanwhile, Bredesen has put these 230 peer-reviewed studies on his CV and is using them as proof that his method works, pushing out lucrative clinics across the country. The trouble is, just as not all studies are created equal, nor are medical journals. There’s a dark underbelly in medical publishing which Bredesen has chosen to exploit, publishing in a section of the medical press that might be best described as “predatory journals”. These journals are best thought of as financial scams, says Dr Richard Smith, former editor of the BMJ and author of the book, The Trouble with Medical Journals. The publishers will publish your study for a fee; there is no peer reviewing or editing involved.

In other words, unwary doctors, journalists, patients and families can easily be misled into thinking a published paper in a medical journal is a sign of quality when it may simply be a sign that the author has paid to be published.

“When predatory journals first appeared more than a decade ago, it was widely assumed that authors published in them because they had been deceived,” says Smith. “But it’s become apparent that many authors chose to publish in them because they know that the paper will be published. The authors can put the papers on their CVs, and appointments committees or grant-giving bodies will not know that the reference is to a predatory journal,” he explains.

This isn’t the only place where the medical establishment has opened a rich seam for people such as Bredesen to exploit. Those complicated financial relationships between dementia charities and the drug companies manufacturing the new treatments have proved useful for Bredesen. He has called out the Alzheimer’s Association for praising the medical treatment aducanumab, after it received a significant amount of money from the drug’s manufacturer, Biogen. As Bredesen phrased it: “Well yeah, they were paid over a million dollars. No kidding they thought it was a good drug. It’s been surprising how incredibly powerful the infrastructure of money making is.”

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So, how do patients and families work out who is offering treatment that might be worth the money — especially when clinics are run by bona fide, GMC-registered doctors? As we have seen, medical journals aren’t all sound — just because something has been published doesn’t necessarily mean we should take it at face value — and it also seems that those who are supposed to uphold the integrity of medicine might not necessarily be protecting patients either.

We told the Advertising Standards Authority (ASA) about the claims Greenland Medical Centre were making in November 2023, who agreed they should be changed and they referred our complaint to the compliance team. However, six months later, Greenland Medical’s website still says they can “reverse the cognitive decline of early Alzheimer’s disease”.

We also raised our concerns with the General Medical Council, the doctors’ regulator, that false claims were being made to a potentially vulnerable group of patients by a registered doctor. The Council refused to investigate, saying “no information has been provided to show that the treatments offered by the doctor are a danger to patients” or that “patient safety is at risk”. They also said that “It does not seem like the information provided that there is clear indication Dr Greenland has been deliberately dishonest about the treatments and what it offers to patients.”

Instead, the GMC told us to raise concerns with the Care Quality Commission, which we did, in November 2023: they have yet to respond.

Dr Greenland told us: “We are prepared to engage with the Advertising Standards Association to ensure that our communications are in compliance and accurately represent the scientific evidence supporting the protocol.” They also stated that “the Bredesen Protocol represents a novel and evidence-based approach to Alzheimer’s treatment”.

There are people in public health medicine who are providing credible, useful work. Professor Carol Brayne, for example, says that we should have a more holistic approach to looking at Alzheimer’s rather than focus on individual theories. “What the clinics are doing is trying to package all interesting hypotheses that are out there,” she says, “as well as sensible stuff that’s been around for centuries and put them all together as a magical prevention package. There is some reasonable stuff mixed up with speculative stuff.”

But the truth is that there is no magic cure, and we should be honest about this and the ongoing need for high quality research. Considering the potential to exploit people, the lack of effective regulation around highly priced but ineffective interventions for people with cognitive issues is deeply troubling. Caring for patients with dementia should also mean protecting them from false, expensive hope. Our regulators need to proactively step up.

But is banning anything a good idea? It’s worth looking at the numbers a bit. The links between head injuries and dementia among professional sportspeople are in the news quite a lot, but I think the risks and the certainty of the science are sometimes overstated, and it could put people off playing sports, which is unambiguously good for you on the whole.

The comment piece I just linked to points out that professional footballers were at a 350% increased risk of death from neurodegenerative disorders, Alzheimer’s being the main one. And that is absolutely true.

However, as I’ve said on one or two occasions, learning about the increase in relative risk is no use for helping you make decisions. If your risk of something goes up from one in a billion to 4.5 in a billion, that’s a 350% increase, but you might not care about it very much.

In this case, the “absolute risk” of neurodegenerative disease among the control population was 0.5%; among the Scottish footballers it was 1.7%. That is indeed a 345% increase, but in real terms, it means that if you’re a Scottish professional footballer, there’s a 1.2% chance that you’d die of a neurodegenerative disorder that you wouldn’t otherwise have died from.

That is not a negligible or irrelevant thing — a one-in-80-or-so chance of getting a horrible disease like Alzheimer’s is worth being aware of. But it’s much less scary-sounding than “a 350% increase”.

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Also, we should note that these players mainly played a long time ago, in football terms. Their median age was about 65, suggesting that they would have retired at least 30 years ago, and in many cases much earlier. The rules of football have changed significantly in that time; balls have become lighter; the pitches have become smoother and more amenable to passing along the floor; and I think it’s fair to say that the influence of Wing Commander Charles Reep has waned, and players are less likely to lump it to the big man up front these days. It’s far from obvious that the risks of heading are the same as they once were.

That’s assuming that heading is indeed the cause of the problem, of course. The working theory is that repeated mild trauma causes something called “chronic traumatic encephalopathy”, a sort of steady tearing of small structures in the brain, and that leads to dementia. But it’s very hard to establish; there is still some dispute over whether the condition is real, although I think less so now than when I wrote that piece in 2016.

It was first noticed in American football players, but there was a selection problem, in that the only brains they dissected were those of players who’d shown symptoms of neurodegenerative disease, making it impossible to see whether the background rate was higher than you’d expect.

It could well be that these repeated minor traumas cause CTE, which then leads to dementia; but it’s not as though there are no other possibilities. The new study tried to control for one obvious factor, the socioeconomic status of the footballers — neurodegenerative disease, like so many other illnesses, is linked to poverty — but they don’t seem to have controlled for other things, such as alcohol use.

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It would not be surprising to learn that footballers drink more than the average person. Alan Carson, a professor of neuropsychiatry at the University of Edinburgh who’s worked extensively on the links between head injury and dementia, told me that quite a lot of the ex-pros went on to become publicans, for instance, which was a common career move.

Of course, you could say that even though we can’t be sure, there’s still no need to be reckless — the precautionary thing to do would be to ban heading in football.

I would be sceptical of that, though. For one thing, heading is a beautiful part of the beautiful game and it would be poorer without it. There are already very sensible precautions against concussion, including the change in the ball itself. More importantly, though, if we make a big deal of it, then I worry it will scare people off playing sport outside the professional game — and that would be a catastrophe.

Something that hasn’t been hugely reported in coverage of the study is that, in general, the footballers were healthier than the control population. They were less likely to die of heart disease or lung cancer, and in fact were less likely to die of all causes below the age of 70 (their mortality rate over the age of 70 was higher). Playing football appears to be protective. And that’s exactly what you’d expect, because sport is unambiguously good for you.

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Carson says that the study — led by William Stewart of the University of Glasgow — is well-executed and thoroughly interesting, and that it contains hints that do suggest a causal link with heading the ball: one point is that goalkeepers, who presumably head the ball less, were slightly less likely to die of dementia. “This is by far the best available data, and the team should be congratulated,” he says. But he adds that Stewart’s previous work suggests that CTE might not be the cause, and that the whole pathology is more complicated than that.

I don’t think anyone would suggest that we stop taking concussion or head injury in sport seriously. But it’s important to note that this data comes from professional sportspeople, playing in a less cautious era with heavier balls and different tactics, and even in that situation the overall effect of playing seems to have been to keep them healthier — and we can’t really be sure that headers are the problem anyway.

My worry is that the vague idea that Football Causes Head Injuries Which Cause Dementia will filter its way into the public consciousness, but there is absolutely no reason to think that this has any impact on amateur players, while there is loads and loads of evidence that sport keeps you fit. Exercise is good for your cardiovascular system, so it protects you against dementia specifically. If you want to avoid getting Alzheimer’s, it’s almost certainly better to play football than not.