The #G8Dementia Summit: a lack of cure for dementia, and tough on the causes of the lack of cure

The setting for today’s #G8Dementia Summit was in Lancaster House, London.

setting G8 dementia wellbeing blog

Many thanks to Beth Britton, Ambassador for Alzheimer’s BRACE and campaigner, Anna Hepburn at the Department of Health, and Dr Peter Gordon, Consultant and expert in dementia, for helping understand, with the excellent livestream from the Department of Health, what challenges might be in store for global dementia policy in the near future.

My account is @dementia_2014

The final G8 Summit Communique is here.

The G8 Summit Declaration is here.

There’s a bit of a problem with global dementia policy.

The patients, carers, families, businesses, corporate investors, charities, media, academics (including researchers) politicians, all appear to have different opinions, depending on who you speak to.

Peter Dunlop, a man with dementia of Alzheimer type, received a standing ovation after his speech. He had explained his reactions on receiving a diagnosis, and how has tried to continue enjoying life. He had been a Consultant Obstetrician and Gynaecologist.

The people with dementia who appeared did indeed remind the audience, including Big Pharma, why they were there at all.

And that there was more to life than medications:

And this was sort-of touched on even by the Prime Minister:

And personhood was not completely lost on David Cameron MP:

And this was indeed music to the ears of people like me, and countless of persons with dementia, their carers, friends and relatives, for example:

And the carers were listening carefully too..!

There was some concern aired that the volunteers and charities would been seen as a valid alternative for a properly supported health and social care system. Whilst everyone agreed that ‘dementia friends’ and ‘dementia friendly communities’ were worthy causes, everyone also agreed that these should not replace actual care.

Part of the aim of today was to foster of culture of diminishing stigma. And yet the media had been full of words such as ‘cruel disease’, ‘robs you of your mind’, ‘horrific’. So the politicians seem conflicted between this utter armageddon and wishing to destigmatise dementia, with generally pitiful results.

Some of the language in the last 24 hours has indeed been truly diabolical. I took a break to watch the main news item on the BBC, and Fergus Walsh was heading up the main item on dementia with extremely terrifying language.

But the Summit kept on reverting to the ‘real world’, pretty regularly though.

A pervasive theme, brought up by many health ministers and other interested parties, was how dementia carers themselves needed supported. Dr Margaret Chan even later in the day spoke about a new online resource for carers, which would be fantastic.

An aspect of why this situation had arisen was not really explained. Prof Martin Rossor, Honorary Consultant for the Dementia and Cognitive Disorders unit at Queen Square, described the dementia issue as ‘a wicked problem’ on the BBC “You and Yours”. However, Dr Margaret Chan from WHO was much more blunt.

Big Pharma had failed to ‘come up with the goods’, despite decades of trying.

But few speakers were in any doubt about the societal impact of dementia, though much of the media resorted to scare tactics as usual in their messaging.

The speakers on the whole did not wish to discuss how care for people could be reconfigured. The disconnect between the health and social care systems is clearly  a concern in English policy. And indeed this was even raised.

All was not lost regarding wellbeing.

Hazel Blears, Labour MP for Salford, explained how her mother was living with dementia, so it was vital that policy should do everything it could do to help people live with dementia.

I met the Salford Institute for Dementia, a brand new Twitter account, for the first time this afternoon, which was in fact one of the highlights of my day.

Although not pole position compared to ‘cures’ and ‘disease modifying drugs’, it was clear that the #G8summit were keen to support assistive technology, telecare and telemedicine. This could be in part due to the generous research grants from various jurisdictions for innovation, or it could be a genuine drive to improve the wellbeing of persons living with dementia.

At just before lunchtime, I suddenly “twigged it”.

I must admit I was angry at myself for having been “slow on the uptake”.

As it was, the discussion appeared to swing periodically between two ends of an extreme during the course of the day. At one end, the discussion was about ‘big data’ and ‘open data’ sharing.

Vivienne Parry , then said how she preferred the term ‘safe data’ to ‘open data’, but Twitter was at that point awash with queries as to whether a rose by any other name would smell as sweet?

People conceded the need for persons and patients voluntarily to contribute to these data sets, and for international organisations such as WHO to attempt to formulate standardised harmonised templates for these data. At the other end, people were very keen to talk about genetic information, presumably DNA, being the subject of DNA genomics data scrutiny at a personal level.

Also, the discussion itself swung from personal tales (such as Beth Britton’s) to a discussion of looking at societal information as to what sorts of data clusters might show ‘susceptibility’ in their genetic information decades before the onset of clinical dementia. Big data, like 3D printers, has been identified as ‘the next big thing’ by corporates, and it’s no wonder really that big data should of interest to big Pharma corporates.

Having failed spectacularly to have produced a cure or disease-modifying drugs across a number of decades, Pharma are left with two avenues. One is that they look at the individual response to therapy of drugs at a single case level using radio-active binding studies (radio-ligand binding studies), and monitor any slowing of build-up of abnormal protein in the brain as a response to treatment. How much this actually benefits the patient is another thing.

Or Big Pharma can build up huge databases across a number of continents with patient data.  Researchers consider this to be in the public interest, but patients are clearly concerned about the data privacy implications.

Here, it was clear that Big Pharma could form powerful allies with the charities (which also acted as patient groups):

And of course this agenda was very much helped by Sir Mark Walport being so enthusiastic about data sharing. Having been at the Wellcome Trust, his views on data sharing were already well known though.

If it were that regulators could allow  data sharing more easily, justified presumably on public policy grounds such that freedom of information was more important than data protection according to the legal doctrine of proportionality, this plan could then considerably less risky for corporate investors wishing to invest in Big Pharma.

Andrea Ponti from JP Morgan gave this extremely interesting perspective, which is interesting given the well known phenomena of ‘corporate capture’ of health policy, and ‘rent seeking behaviours’ of corporates.

It has been argued that waiting for valid consent from the patients would take too long, so presumed consent is more of a practical option. However, this ethically is an extremely tricky argument. The Pharma representatives were very keen to emphasise the ‘free flow’ of data, and the need to ‘harmonise regulation'; but they will be aware that this will requiring relaxing of the laws of more than one country.

And so, during the course of the day, the agenda of Big Pharma became clear. They intended to be tough on the lack of cure for dementia, and tough on the causes of that cure. Some might say, that, as certain anti-dementia drugs come to the end of their patents (and evergreening is not an option), they have suddenly converged on this idea to tackle dementia, as it is a source of profitability to enhance shareholder dividend. They now need new business models to make it succeed (and various charities and research programmes which benefit from this corporate citizenry might be able to make it work too.)

But during the course of the day those ‘pesky’ tweets about person-centred care kept on coming…

Some of the tales were truly heart-breaking.

But I was happy because Beth was happy at the reception of her film. She is so utterly passionate, and totally authentic, about the importance of her father who had dementia. It was a privilege for us to see how well the film had been received by all there at the #G8summit.

And those pesky tweets kept on coming…!

But indeed there was a lot to be positive about, as research monies if well spent could provide a cure or disease-modifying drugs. Big Pharma and the researchers know that they are not only trying to tackle the big one, the dementia of the Alzheimer type, but also other types such as the vascular dementias, frontotemporal dementias and diffuse Lewy body disease.

Beth’s input today was invaluable.

And Dr Peter Gordon loved it!

But the best comment of the day must certainly go to Dr Margaret Chan, a V sign to those obsessed with Big Data spreadsheets and molecular biologists looking at their Petri dishes:

In summary…

It smelt like a corporate agenda.

It looked like a corporate agenda.

It sounded like a corporate agenda.

And guess what?

All the ingredients of ‘corporate capture’ were in attendance: big data, personalised medicine, genomics, data sharing. They’d have managed a full house had the world leaders found a use for 3D printers in all of this.

Is a new sophisticated brain scan desirable to diagnose dementia?

Amyloid plaques

Wouldn’t it be lovely Prime Minister, David Cameron MP, could announce a breakthrough which nails the problem of the diagnosis of Alzheimer’s disease?

The definitive diagnosis of dementia of the Alzheimer type (DAT) comes post mortem (though in practice various techniques while the patient is alive can be used to tell whether a patient has a type of dementia).

The full armoury of tests includes thinking tests or cognitive neuropsychology, a sample of the fluid from the spine (cerebrospinal fluid), the clinical history and examination of the patient, brain waves (the EEG), or even (rarely) a brain biopsy; that’s even before considering types of scan, like the ‘CT scan’, the ‘MRI scan’, or ‘functional scan’.

The trick of the clinician, varying with levels of expertise, is to make the diagnosis reliably such that a person living with dementia might be able to ‘access’ appropriate care in the system; and those without dementia aren’t given an incorrect label of ‘dementia’.

DAT is one of the hundreds of causes of dementia (although most of the media use ‘Alzheimer’s Disease’ and dementia unhelpfully synonymously.)

Amyloid build-up and the diagnosis

There has been a popular idea that the build up of a substance called amyloid which builds up in the brain might hold the clue to early diagnosis of Alzheimer’s Disease.

In recent years, the emphasis has swung to ‘timely diagnosis’, with the national clinical lead for dementia, Prof Alistair Burns, emphasising that the diagnosis should be made at a time appropriate for the person himself or herself.

A ‘quick fix’ in a test for DAT seems very attractive, but it’s important to remember that the dementia of the Alzheimer type is only one (but the most common) cause of dementia across all age groups.

How to use the test in a safe way

The way in which this diagnosis could be made has also come under scrutiny.  A method which uses a radioactive label to which at how much label can bind to abnormal amyloid in the brain, to be practical, should not be excessively time-consuming to administer. It also should not be prohibitively expensive.

Also critically, it should be reliable. In other words, it shouldn’t show up ‘positives’ in otherwise well people, who never go onto develop dementia. A critical problem is that there are many causes of memory loss in older people, including of course depression.

To make things even more complicated, there is a very interesting group of people whose thinking and memory are normal, even late in life, yet their brains are full of amyloid beta plaques that appear to be identical to what’s seen in dementia of the Alzheimer type. How this can occur is an important clinical research question.

Hard plaques made of a protein called amyloid beta are always present in the brain of a person diagnosed with the dementia of the Alzheimer type.  But the simple presence of plaques does not always result in impaired thinking and memory. In other words, the plaques are necessary – but not sufficient – to cause DAT.

Is it the type of amyloid which matters?

Earlier this year a paper was published in the prestigious journal in the US (Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM, Brody DL. (2013) Amyloid-β oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol. 73(1):104-19. doi: 10.1002/ana.23748. Epub 2012 Dec 7.)

An important clue may come from still come from a form of amyloid beta, but not necessarily in the form of plaques. Instead, smaller molecules of amyloid beta appear more closely correlated with whether a person develops symptoms of dementia; these are called “amyloid beta oligomers“.

Earlier this year, this group developed a way of measuring  these amyloid beta oligomers in minute quantities, without binding to similar things.

These amyloid beta oligomers were detected in samples of brain from patients with DAT and nondemented patients with amyloid plaque pathology. However, amyloid beta oligomer concentrations in samples from patients with DAT were tightly correlated with amyloid plaque coverage (correlation very high), but this relationship was weaker in those from nondemented patients (correlation very low) despite equivalent amyloid plaque pathology.

The results raise the intriguing hypothesis that the linkage between plaques and oligomers may be a key pathophysiological event underlying DAT.

This test would be clearly potentially profitable for people who have developed this test, and the critical issue is whether if you scan real patients whether the amount of radioactive binding will reliably distinguish between people with dementia and those without.

Would a new brain scan be helpful?

Looking for amyloid in people who might be developing dementia has been a story going on for ages. The Telegraph newspaper reports a “breakthrough” in a scan, but the description is that of plaques (leading to the possibility of people having lots of plaques found on imaging who later never develop dementia):

“The scan was developed by scientists in London. The test involves giving a patient exhibiting signs of dementia a small amount of a radioactive substance, which will allow amyloid plaques to show up in a brain scan.

The presence of the plaques in the brain is one of the main signs of Alzheimer’s, although it does not make the disease inevitable, so doctors using the test would be sure of giving a patient the all-clear only if the plaques were absent.

It is the first time doctors have been able to detect the plaques while a patient is alive.”

The desire ‘to catch Alzheimer’s early’ – and the actual pitfalls

A major issue is going to be which people should be put forward for such an imaging technique; there has been intense scrutiny of whether bedside tests can reliably tell the difference between people who have a ‘mild cognitive deficit’ and those who have dementia.

A political drive, almost in total parallel led by the current UK and US governments, to “screen” older people for minor memory changes could potentially be leading to unnecessary investigation and potentially harmful treatment for what is arguably an inevitable consequence of ageing. There are no drugs that prevent the progression of dementia according to human studies, or are effective in patients with mild cognitive impairment, raising concerns that once patients are labelled with mild cognitive deficits as a “pre-disease” for dementia, they may try untested therapies and run the risk of adverse effects.

The idea itself that there is a “pre-disease” stage before the full-blown course of the dementia of Alzheimer type is itself erroneous, if one actually bothers to look at the published neuroscientific evidence. A mild cognitive impairment (“MCI”) is a clinical diagnosis in which deficits in cognitive function are evident but not of sufficient severity to warrant a diagnosis of dementia (Nelson and O’Connor, 2008).

However, the evidence of progression of MCI (mild cognitive impairment) to DAT is currently weak. This has been much to the frustration of some researchers where it had been hoped for years that this could be used to identify DAT at an early stage. It might be attractive to think that MCI is a preclinical form of dementia of Alzheimer Type, but unfortunately the evidence is not there to back this claim up at present: only approximately 5-10% and most people with MCI will not progress to dementia even after ten years of follow-up (Mitchell and Shiri-Feshki, 2009).

It’s the post-diagnosis support anyway…

Either way, there should still be adequate post-diagnosis support, which is a problem which simply won’t go away.

Therefore, this result of a ‘breakthrough’, for one of the more common causes of dementia, has to be sufficiently exciting for the drug companies to have a ‘return on investment’ who have developed them.

However, in a week which has seen increasing scrutiny as to whether pharmaceutical-based approaches have been a waste of dawn, particular interest will be paid as to whether this is in fact yet another “false dawn”.

Other references

Mitchell, A.J., and Shiri-Feshki, M. (2009) Rate of progression of mild cognitive impairment to dementia -meta-analysis of 41 robust inception cohort studies. Acta Psychiatr Scand, 119(4), pp. 252-65.

Nelson, A.P., and O’Connor, M.G. (2008) Mild cognitive impairment: a neuropsychological perspective, CNS Spectr, 13(1), pp. 56-64.