Have doctored images led to 20 years of wasted Alzheimer’s research?

Anyone who has watched Casualty or 24 Hours In A&E, or read a book about life as an emergency doctor, would expect my job — as an A&E consultant — to be filled with dramatic life and death situations; stabbings, car accidents and cardiac arrests.

But the reality is that I spend most of my time dealing with the impacts of ageing and societal problems such as smoking, diet, drugs, alcohol, loneliness and poverty. These are the ‘slow burn’ problems that send people to A&E when there’s been an acute exacerbation of a general decline.

And one of the most common types of patients we see in A&E departments are those with gradually worsening dementia; somehow managing to cope at home until the day he or she develops a urinary infection, falls over and needs admission for antibiotics and rehabilitation.

Dementia is the disease we now all fear most, more than cancer.

Recalling the excited headlines recently about ‘breakthrough’ Alzheimer’s treatments, the good news is there’s a drug that can sort dementia — so you’d think that, soon, this won’t be a problem any more; we don’t need to worry.

Yet what if this isn’t what it seems? What if the principle underlying the years of research and billions spent on developing these drugs is based on faked data? What if all that money— and time — could have been better spent on looking for other treatments?

Today, in the first of a regular column, I’m going to explain what’s really going on behind the latest health news stories — starting with ‘potentially falsified’ data that lies at the heart of dementia research — unravelling the science to help you make informed choices about your health and medical care. Because the days of accepting blindly what you are told should be banished to history.

The fact is, doctors don’t always have the right answers, and while you’d expect them always to practise evidence-based medicine, it’s not so simple.

Often, there isn’t the evidence available. Or even if there is, it is not always adopted by the medical community.

The most disastrous example was the pioneering work of Ignaz Semmelweis, a doctor working on midwifery wards in Austria more than 150 years ago.

In 1847, death rates at his hospital among women looked after by midwives were far lower compared to a ward where the women were treated by male doctors and students, who would deliver babies after dissecting cadavers.

Dr Semmelweis proposed that doctors should wash their hands with a chlorine solution. This led to a decline in deaths to the point that doctors and midwives had the same patient mortality rates.

What a hero! Except the other doctors didn’t like hearing that they were (inadvertently) responsible for their patients’ deaths, so they banished hand washing, and Dr Semmelweis was forced out of his job. And the death rate went back to where it was before.

Twenty years later, Dr Semmelweis died in a mental asylum, an outcast from the medical community. It took another 40 years for the medical profession to accept his evidence and approach. But in the meantime, thousands of lives were lost.

Scientists and doctors are also motivated by the need to burnish their reputations, driven to publish positive trials to continue to get funding from pharmaceutical companies. Plus we have to factor in unconscious ‘bias’, where researchers subconsciously only look for evidence of what would support their beliefs, discounting other evidence.

I’m going to explain what is really going on behind the latest health news stories – starting with ‘potentially falsified’ data that lies at the heart of dementia research 

And then there’s the evidence that’s simply made up. This happens a lot: plenty of journals have had to retract papers because the authors misrepresented the evidence, or simply cheated it. Few readers will have forgotten the story of Andrew Wakefield, who concocted data to show the MMR vaccine caused autism.

It is in this tricky area that we come to dementia. For a long time we’ve thought that Alzheimer’s is caused by a build-up of a protein called amyloid in the brain — and literally billions of dollars and decades of researchers’ efforts have been poured into pursuing this understanding.

And, apparently, it’s all been worth it, with the recent announcement of a drug called aducanumab (brand name, Aduhelm) that reduces a build-up of amyloid plaque.

This drew excited headlines around the world.

But since then, the European Medicines Agency, which reviewed the trial data, has said there was currently ‘insufficient evidence that aducanumab was safe, effective and had clinical benefit for people living with Alzheimer’s’. At more than $28,000 (£23,000) per patient, per year, with side-effects such as brain swelling or bleeding, all that glitters isn’t necessarily gold.

More recently, another drug, lecanemab, which also tackles amyloid, was announced to great fanfare. While it may slow down cognitive decline in early Alzheimer’s, it’s not clear it will actually make a difference to patients — and it, too, had side-effects in the brain.

Which takes us back to my patients with Alzheimer’s. Why have the treatments for this awful condition not substantially progressed in the past 20 years — despite so many resources being pumped into it?

Maybe it’s because our efforts have been focused on one area — and wrongly, it may seem.

In 2006, research in the respected journal Nature appeared to show evidence that Alzheimer’s might be caused by deposits of amyloid, subtype 56.

Money was pumped into creating drugs that break up these particles, but the impact on patients’ wellbeing has been limited, to say the least — even with the new drugs, as I’ve explained.

Why is this so? In 2021, Matthew Schrag, a neuroscientist and physician at Vanderbilt University, looked into the original research. He found evidence that the original images that led to the conclusions in the research were apparently doctored.

Why have the treatments for the awful condition of Alzheimer’s not substantially progressed in the past 20 years?

It’s a story that rocked medicine, and last July, Nature put a warning on the electronic versions of the original research, stating: ‘The editors of Nature have been alerted to concerns regarding some of the figures in this paper.

‘Nature is investigating these concerns and a further editorial response will follow as soon as possible. In the meantime, readers are advised to use caution when using results reported therein.’ We are still awaiting that ‘further editorial response’.

So what? Actually, potentially, this matters quite a lot.

This paper has been cited by 2,288 scientific papers and has had an impact on a whole generation of researchers.

In the meantime, other factors may have been overlooked, such as lifestyle, immune dysfunction, levels of glucose [sugar] in the brain, or inflammation — all given less prominence by the research community in order to continue pursuit of targeting that specific amyloid subtype.

These other factors, as we know, are significant. Just last month, results from a 20-year study of more than 13,000 women in the U.S., showed that simple lifestyle changes — such as physical activity, maintaining a healthy diet and weight, not smoking, and keeping blood pressure, cholesterol and blood sugar levels in check — can reduce the risk of dementia by up to 42 per cent, which is massive. (This is probably because these help reduce inflammation, a prime driver of disease.)

Another interesting study, from the University of Delaware, just published in the journal Aging Cell, showed that taking a tablet of a naturally occurring substance, nicotinamide riboside (a form of vitamin B3), can increase brain levels of a substance called NAD+, which slows down the ageing of cells.

It also lowers levels of two proteins, pJNK and pERK1/2, which seem to raise glucose levels and inflammation in the brain. Maybe, in years to come I’ll be prescribing nicotinamide to my patients.

What’s important now is that honest research is done. That way, if the risks of the drugs outweigh the benefits, we can re-focus research ideas into other avenues.

So what does this all mean for you now? My message is: don’t hold out hope for a ‘wonder’ drug that might — or might not — make a difference in Alzheimer’s. But there is one thing we know works 100 per cent: lifestyle adaptations.

So take care of yourself — and keep an eye out for my next column in a couple of weeks’ time!