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Rethinking Alzheimer's - James Fletcher


James Fletcher

James Rupert Fletcher is a PhD student at the Institute of Gerontology in the Department of Global Health & Social Medicine at King’s College London. He is currently researching informal care from the perspectives of people with dementia living in the Midlands, UK. He is interested in interpretative approaches to dementia, as well as dementia research more broadly. He is also interested in the health and social care divide and ageing. His work is informed by symbolic interactionist and antipsychiatrist ideas, as well as social theory more generally. 



Hello, I’m Nigel Warburton. Joining me today is James Fletcher, an ESRC sponsored PhD student in the Department of Global Health and Social Medicine at King’s College London. James, we’re focussing on Alzheimer’s, why are you focussing on that rather than other forms of dementia?

Alzheimer’s is the leading cause of dementia, so obviously it’s quite a biggie. It causes around 60% of dementias so it’s a real serious chunk of all dementias. I focus on Alzheimer’s because, it’s a good inroads into explaining why factors other than biology and pathology are important in terms of looking at dementia in general, because the biomedical model of Alzheimer’s, and the medical understanding of the causes of Alzheimer’s disease, are currently fairly inadequate.

My children describe Alzheimer’s as old-timers disease, through mishearing it. In a sense it’s always been around and people have talked about it as a natural process of ageing. Has that ever been put forward as an explanation?

Your children are picking up on something very important there, in that throughout most of human history, Alzheimer’s disease and dementia in general, as a set of symptoms of cognitive decline and people’s brain power declining showing these symptoms, that has been assumed to be a natural part of growing older. It’s your second childhood; you will inevitably get old and your cognitive capabilities will decline. And it’s only very recently in terms of human history that that has been challenged. 

And the challenge has led to medical models where people get precise about causes and they start to identify particular features of the brain that pre-dispose people to Alzheimer’s?

It was originally developed by Alois Alzheimer, who eventually gave his name to the disease, and it was, even back then at the turn of the twentieth century, a condition that was a disease in younger people, and was normal in older people. So there was still a distinction. And it actually took half of that century for that distinction to be removed by developments in electron-microscope technology looking at brains and saying, “Well there’s the same process going on whether you’re fifty years old or seventy years old, so maybe it’s quite arbitrary to say that it’s normal in older people and that it’s abnormal in younger people.” 

So what is that process?

The model that’s currently most followed, and most advocated by the scientific community, is the amyloid cascade hypothesis, which is basically this protein called beta-amyloid accumulating in your brain, and that’s colloquially referred to as “plaques”. You hear a lot about plaques and tangles in dementia and tangles are another type of protein that are building up and causing neurofibrillary tangles, they’re tau tangles. But these beta-amyloid plaques are attributed to Alzheimer’s because you chop up a lot of brains and you see they’re littered with these plaques and it looks quite messy, it’s quite a visual thing

That seems like a plausible hypothesis, that the plaques are causing the symptoms?

Firstly, there’s the issue of, if you look at a brain and you know the person died with this certain disease, and their brain is full of these abnormalities, then it’s a very natural response to say “Okay, those abnormalities cause that disease”. And obviously, logically, you can’t assume that causation; correlation is not causation. It could, of course, be that they are a protective measure. Alzheimer’s disease could be something that happens and then these beta-amyloid proteins accumulate to protect the brain from the damage. And then, they could have nothing to do with it at all, they could just naturally be there. So the problem is that there has always been a disparity between pathology and symptoms, and so for a long time this was evident only at post mortem because that was the only way you could get a good image of the brain. So you’d chop up the brains of these people who’d died with a diagnosis of Alzheimer’s disease and you’d see they’d be littered with these plaques. But there’s a massive disparity in that, you can chop up the brains of older people who died and they were really on the ball, they knew what they were doing, doing their Sudoku every day, and they’re also littered with these plaques. And this can be a 30% disparity so we’re not talking about rare cases; we’re talking about a very significant percentage. 

Well there could be an alternative explanation that some people have the capacity, through the plasticity of the brain, to engineer around the problems as it were, and other people don’t. So it could still be that the plaques are the causes of dementia, it’s just that some people have a kind of prophylactic against that?

And certainly, this has been suggested many times by the medical community, and that rests on the assumption that if you have an eighty year old whose brain is displaying a lot of beta-amyloid plaques, then they do have some sort of capacity to deal with that, and maintain the outward show of being very cognitively able. But if they were to survive until, say, one hundred and twenty, then inevitably this disease process is going on and it will eventually lead to symptoms. 

So in a sense that might be begging the question, because it’s assuming that the explanation is correct without actually testing alternative hypotheses.

Yeah, and so the problem with this is that now there have been drug trials that have removed beta-amyloid plaques from the brains of people displaying these symptoms, and they’ve not had any effect in terms of symptoms. People have still then subsequently died, still displaying severe symptoms. 

Couldn’t that be because the damage had been done, as it were, that it wasn’t reversible?

And so, this is now a new direction that we see medicine move in, in that we get a pre-symptomatic expansion whereby people are saying “okay, we removed the plaques and that didn’t do anything so maybe we’re too late, the damage has been done, and what we need to do is remove these plaques  twenty or thirty years earlier”. And we see this in terms of early diagnosis. Within the entire field of dementia there’s a feeling that we need to know when people are getting it earlier and earlier, so that we can target it and prevent these things accumulating.

Well that sounds quite reasonable doesn’t it? I mean, we may have to wait twenty or thirty years to see if the science works but that, again, seems like a reasonable way to approach the issue.

So I guess again, the issue with that is that it’s untested really, and it’s hedging bets to a massive extent, before you even get to the issue of medicalising populations. I mean, if you start to talk about a pre-symptomatic Alzheimer’s disease, that has huge huge connotations. If you tell somebody at the age of forty that “in thirty years’ time you will be severely demented”, what does that do in terms of their health insurance, in terms of their ability to have a driving license, getting jobs? What happens with that? And if we talk about social theories, about what it means to be medicalised and how people react to that diagnosis, then you could be, in effect, perhaps causing more Alzheimer’s disease by labelling these people very early on and telling them.

Well there must be environmental factors at play in who develops Alzheimer’s, but presumably there are also genetic factors

So when the scientific community was first really coming to terms with the fact that ageing brains present these very similar physical traits to the brains of those with Alzheimer’s disease, one of the ways that they started to come to terms with that was to say that “well ageing is getting in the way”. It’s almost “we want to examine Alzheimer’s disease in its pure form that we can classify and then study. And when you study it in people who are ageing, it’s mixed up with ageing which has a similar physiology, and it’s very messy and we can’t quite distinguish what we’re looking at in terms of a disease and what we’re looking at in terms of physiology”. So what they do, is they turn to these very rare populations and these very rare families that have gene mutations that very consistently and predictably cause early onset Alzheimer’s disease. And these are caused by three genes, two of which, if you have them you’re going to get Alzheimer’s disease at a young age, and one of them you have, still, a massively high probability, so it’s still worth studying. So they get this abstract, pure Alzheimer’s disease, and if it’s in a thirty or forty year old it’s not messed up with ageing and you can look at it quite nicely under a microscope and it’s very distinct. So what we’re talking about with those populations is a very very rare group. I mean, we’re talking nought-point-something percent, tiny. And so then what’s happened is that genetic causation has been taken and mapped onto the rest of people with Alzheimer’s disease, which is the mass majority. And so we have what is called the APOE gene, and there’s a bad version of that, and if you have these two bad versions together, then that increases your risk of getting Alzheimer’s disease. The only problem is, and I mean this is very similar to what they’ve found in mapping the human genome, is that it’s not that simple. You don’t just say “you’ve got ABC genes so you end up ABC”, it’s not that direct causality. And it’s now got to the stage whereby the more you look at the APOE gene and other environmental factors, the other things that other genes in the body are doing and the way that they’re expressed, having those genes  now can’t reliably inform even a risk estimate, let alone anything else. So it’s got a long tail of, the more you look at it, the more useless it becomes.

It seems to me from what you’ve been saying that there are complex causes of Alzheimer’s, and it’s difficult to disentangle a real cause in any particular case, or the principle cause. Presumably there are also environmental factors which mask the extent to which somebody has Alzheimer-type changes going on in their brain?

There’s the often repeated cognitive reserve hypothesis, which basically states that if you have a high level of education and you’re functioning at a high cognitive level, then if you imagine there is a set level of cognition at which you start to display symptoms and people start to think “well actually that’s Alzheimer’s disease”, then having a lot of cognitive capacity means that you’ve got much further to fall than someone who has low cognitive capacity before you hit that cut off point, that sort of event horizon of Alzheimer’s, at which you’re then symptomatic.

So you’ve talked about the traditional way of explaining the symptoms, about Alzheimer’s as just a natural product of ageing, we talked about the plaque hypothesis, we talked about genetic factors. What have we left out?

What seems to me as a correct approach, moving forward in Alzheimer’s disease, and this applies to dementias more generally, is the public health model and here we’re talking about things like education. And they’re also linked to things like diet, exercise. If you look after your cardiovascular system, you’re looking after your brain, and so you’re less likely to start displaying symptoms as you grow older. One thing that seems to be missed out as all of these things are proposed and people start to realise that it’s not a single point, or a small set of points, but it’s everything taken all together, and very holistic, is the social interactive elements that have been very much brought into the broader field of dementia by people like Tom Kitwood and Sabat. They’ve done a lot to bring the social theory around interaction into dementia, but it always seems to focus on, sort of, the care. The people are already in care home and then how staff can interact with them in terms of person-centred care. And you know, this has very positive outcomes. I mean it seems almost common sense to say that if you treat people well and as people, they act more as people and less as people with dementia. But again, that’s seen as somehow separate to this other fight that’s going on to cure or prevent it. And so what my research will be looking at is using these forms of social interaction, very much informed by social theory, as perhaps something that can start much earlier on, perhaps the ways in which people are interacting with older people in general. Because if you look at the portrayal of older people and the portrayal of dementia in things like the media, then you can see a lot of parallels in the alarmism and the negative imagery. You know, they’re going to collapse the economy, burden, all of these sorts of things come out, the rising tide waiting to overwhelm the health and social care system. And these things aren’t accurate and they need to be addressed because they’ve very much entered the popular imagination.

So are you suggesting that the actual stereotype of dementia, or of Alzheimer’s, is a contributing factor to the expression of biology?

Massively so, and it’s interesting the sense in which certain writers have picked up on the way that research needs to reiterate these negative stereotypes to gain funding. Because if you say “I’m going to do a study, looking to target beta-amyloid”, then that’s quite mundane. But if you’re going to do a study looking at a potential cure for Alzheimer’s, which is going to effect this many people, and it’s going to cost this much, and it’s going to have this burden and that burden to millions of people and carers, then all of a sudden that gains a lot of attention. And that needs funding, and the public are thinking “well the government needs to plumb money into this because it’s going to be a disaster”.

So are you suggesting that there’s a kind of rhetoric of grant applications which affects the explanations that people will give for Alzheimer’s?

Yeah, and it’s interesting that when I first came to the subject I assumed, and I think it’s quite a common assumption, that it’s media sensationalism, and that they’re the ones that are propelling this, what we call, apocalyptic demography, that the grey hordes are coming to destroy society. And then you delve down into the actual research and it does reiterate it itself. And the medical papers and things like that, they reiterate this view. It’s not necessarily the fact that the media reads something mundane and then sensationalises it, it’s already there as a tool of garnering attention. And I’ve done it myself, certainly, a couple of years ago. And I think lots and lots of papers, even in the social sciences, they’ll begin with “dementia does all these bad things, it affects this many people”. And there’s this massive appeal to the pure numbers of it, the staggering millions. 

I know you’re just at the start of your empirical research, put what do you hope to find?

I very much view Alzheimer’s disease, and dementia more broadly, as something that’s going to be overcome by a combination of many tiny steps. And there will be massive medical contributions to that, and there will be psychological contributions, social contributions, education, public health, all of these things matter. And what I hope to do is develop, in some small way, one of those social steps, which perhaps won’t even be limited to dementia and Alzheimer’s disease. It will just be, more broadly, a better way of treating older people.

James Fletcher, thank you very much. 

Thank you, Nigel.


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