An audience with Prof Dale Bredesen at the Royal Society of Medicine

About 27 years ago, I had lunch with a guy who claimed he had invented cold fusion in a test tube, offering unlimited energy at room temperature. His name was Prof Martin Fleischmann, and he had a distinguished career including a chair in electrochemistry at Southampton. I remember him even now. I don’t think that that claim was ever resolved, but I do remember the general mistrust he had received from the scientific community. It was something akin to the treatment of Uri Geller and his extraordinary powers to bend spoons.

I rarely like to go to events these days for personal reasons, but I did manage to make it to Wimpole Street to the Royal Society of Medicine yesterday evening to attend a talk on how a nutritional supplement could ‘reverse cognitive deficits’ in dementia.

The mentor of the speaker, Prof Dale Bredesen, was a man whose work is very familiar to people in my field which is dementia – Prof Stanley Prusiner. Prusiner is prof of neurology at UCSF, and himself was awarded the Nobel Prize for physiology and medicine in 1997 for his groundbreaking work on prions (proteinaceous particles). These particles in the brain can be radically changed in shape from normal to abnormal, causing the brain to die in certain dementia conditions – the most famous of which is Creutzfeldt Jacob  disease, though others exist including kuru and Gerstmann-Slraussler-Scheinker. Prions exist in the normal brain, and one had been left wondering what the normal evolutionary advantage of such biology in the brain is. In 2002, I was then a junior physician on Prof Martin Rossor’s firm – Prof Rossor headed up the cognitive disorders and dementia unit, a post now held by Prof Nick Fox, who used to be our specialist registrar. The variant Creutzfeldt Jacob disease was a very real phenomenon (as it is now) when I was a junior. I remember patients having brain biopsies for their rapidly progressive dementias – it was just after the time there had been concern about the transmission of disease from ‘mad cows’ to men. Indeed Dr Giovanna Mallucci was my Specialist Registrar too, and now is a professor in Cambridge – a lovely person in her own right. I remember doing lumbar punctures for us all normally on a Wednesday.

I dare say there is a fine line between genius and not-so genius. I found Prof Dale Bredesen a lovely guy, very measured and sincere about his research, cleverly reasonable, with a genuine drive to make a difference to people living with dementia. His work is on a personalised medicine to people with cognitive deficits, which he described as not just mnemonic (amnestic) but also perceptual (e.g. in face recognition, i.e. prosopagnosia). And he was merely describing his clear results where patients had vastly improved given a nutritional supplement. Bredesen’s ability is no question – his junior posts included senior positions.

Modern medicine can have massive side effects. Even ‘harmless statins’ can rarely give people crashing renal failure in a condition called rhabdomyolysis. One is left wondering why a natural instinct is to question nutritional ‘interventions’ with seemingly more scrutiny than drugs in our own British National Formulary.

The push-pull effect of this type of research definitely includes the pull away from traditional Pharma research – which has had a disappointing score sheet.

Kate Swaffer, Chair of Dementia Alliance International, talks about a ‘prescribed disengagement’ expected of people newly diagnosed with dementia. Bredesen drew attention to one of the worst aspects which I have found awful from the US jurisdiction, of people unable to take out long term insurance from health maintenance organisations on account of being diagnosed with dementia.

In the US insurance-based system, where hopefully the NHS is not being led despite strong internal forces within our UK politics, if you’re at high risk, an insurance company doesn’t want to take you on for fear of being given a shellacking in paying for your future healthcare needs.

Bredesen I feel is right to question not just the culture of cure from the medical profession and biomedical industry (one which is being challenged in England in an iceberg-level of pace by social prescribing), but specifically the culture of drugs which have been validated through a process of drug trials for monotherapy. I believe firmly dementia’s hallmark characteristics are complexity and multi morbidity, whatever the age group, and this tends to entail polypharmacy. The thing is these drugs are validated in isolation, but it is a bit of a human experiment to guess how they might work in a different age group in combination.

But here Prof Trisha Greenhalgh brings up a good point. Whilst I’m a ‘believer’ in the n = 1 methodology made famous in social psychology research methodology, is this really endorsing anecdotes?

So it seems sensible indeed as Bredesen to tackle like with like, i.e. take a complex approach to a complex problem. In this framing of the narrative, no one size fits all; people are likely to benefit from a complex approach say of particular dietary supplements (or not). The magic bullet approach of acute illness seems fundamentally ill suited to the management of chronic long term conditions, something which the current NHS seems to be acknowledging slowly (but to do so properly will require social care to be adequately respected and funded.)

Prof Dale Bredesen is, though one would be frightened to accuse him so, is in fact caught between a rock and a hard place. He is expected to run larger trials with more ‘power’ to show his effect his real – and yet this approach could annihilate any dramatic benefits he has for particular individuals. This is in a way a general criticism of any approach regarding research in person-centred outcomes. But perhaps doing bigger trials will bring out the heterogeneity in course which does happen certainly in people with Alzheimer’s disease (better called a ‘syndrome’). I asked a question whether he felt he was being forced to make something so complex into a simple narrative, and Bredesen in a typically polite and pleasant manner suggested it was a ‘balance’. Still, the work is being published and the external scrutiny I hope will benefit him and his work.

With so much money ‘big money’ being wasted elsewhere in dementia on what is well and truly rubbish, it seems to me an injustice not to look more carefully at this work. He might be a ‘boat rocker’ in the modern parlance of the Twitter cult, but this might subject him to unnecessary attitudes such as to disenfranchise him and alienate him from the mainstream stream of discussion where I believe he should be. Bredesen talked at one point of reversing ‘Ockham’s razor’ to ‘Razor’s Ockham’, but I feel instinctively the tough nut that Bredesen needs to crack is sorting out correlation from causation. He should not have such a mixed bag of people with dementia and ‘pre-dementias’ such as SCI or MCI, as he can’t take it as given that all people with MCI progress to dementia. This is simply not borne out by the current evidence, howeverso Petersen and influential colleagues decide how to diagnose MCI. There are some people who will get spontaneously better without any intervention – in fact there are some forms of dementia, which have a markedly fluctuating cognitive time-course. One got a twang of these ‘accidental fortunes’ when Bredesen presented a person who had been exposed to a lot of mould at home but had been given therapy to ameliorate cognitive deficit; the issue here is of course how much we are all exposed to mould. Whilst it is important not to confuse correlation with causation, it is equally important for Bredesen not to get side-tracked by confounding variables – it could be a third thing which he feels to be a key feature of some people’s dementias could just be something which is extremely common (take for example the swathe of research looking at whether herpes simplex or cold sores can cause dementia).

Where I feel Bredesen is very right, irrespective of the actual story over this, is the need to ‘see the person, not the disease’, and indeed there could be much to learn here from other cultures.

I found Prof Dale Bredesen very likeable indeed, and genuinely thoughtful. The one concern I do have is one of US medicine in general – of over investigating people – but this is nothing to do with him. I think it is pretty likely in fact that certain lifestyle changes will massively benefit some people in slowing down or even preventing outright the onset of dementia. If this can be done with minimal side effects or draining on scarce resources it is an approach which could be much more equitable than a very costly drug developed from the traditional Big Pharma route. I feel it is the responsibility of people to give this work a fair hearing, and to take it further.

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  • Mary Radnofsky

    Even though person-centered and nutritionally-based, it sounds as though the Bredeson protocol of managing/treating dementia cannot be generalized as a do-it-yourself care system, except in the most general way —- so what’s an American without healthcare to do?

    • wellbeingdem

      Excellent comment – you raise a really really important point. thanks mary
      best wishes shibley