Episode 42      23 min 17 sec
Alzheimer's Disease: Predictors and Early Intervention

Prof David Ames discusses predictors and early intervention of Alzheimer's Disease. With Up Close guest host Jennifer Cook.

"But what we are actually looking for is early diagnostic markers. Things that you can actually take a picture of, or do a blood test on, or get some other kind of test that can say, ‘gee, you’re at risk of getting Alzheimer’s disease in ten year’s time because you’ve got this marker in you.’ " - Prof David Ames




           



David Ames
David Ames

David Ames is University of Melbourne Foundation Professor of Psychiatry of Old Age at St. George’s Hospital Kew, Director of the National Ageing Research Institute, and University of Melbourne Foundation Professor of Ageing and Health.

His main research interests are new drug treatments for Alzheimer’s disease and the care of the depressed elderly. He is Chief Investigator on the $3 million 3 year Alzheimer study funded by CSIRO (Australian Imaging Biomarkers & Lifestyle Study) 2006-9.

David Ames has published over 100 papers in peer reviewed journals. He edited IPA Bulletin the quarterly newsletter of IPA from 1996-2002, he is a member of the Medical & Scientific Advisory Panel of Alzheimer’s Disease International and has been Editor of the Peer Reviewed Journal International Psychogeriatrics since January 2003.

Credits

Host: Jennifer Cook
Producers: Kelvin Param and Eric van Bemmel
Audio Engineer: Craig McArthur
Theme Music performed by Sergio Ercole. Mr Ercole is represented by the Musicians' Agency, Faculty of Music
Voiceover: Paul Richiardi

Series Creators: Eric van Bemmel and Kelvin Param

Melbourne University Up Close is brought to you by the Marketing and Communications Division in association with Asia Institute.

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Alzheimer's Disease: Predictors and Early Intervention

VOICEOVER
Welcome to Melbourne University Up Close, a fortnightly podcast of research, personalities, and cultural offerings of the University of Melbourne, Australia. Up Close is available on the web at upclose.unimelb.edu.au. That’s upclose.u-n-i-m-e-l-b.edu.au.

JENNIFER COOK
Hello and welcome to Up Close, coming to you from Melbourne University, Australia. I’m Jennifer Cook. Many of us dream of living a long, full and happy life, and thanks to the advances in modern medicine people are living much longer than they used to. But considering the growing numbers worldwide afflicted with the debilitating disease of Alzheimer’s, it raises the troubling question: are we trading our once short, sharp existence for a long life of slow decline? With me today is Prof David Ames. He is the director of the National Aging Research Institute at Melbourne University. And he believes that, apart from climate change, the issue of aging is the largest challenge facing the world in the next 50 years. He’s leading a team of scientists in an exciting study, investigating early diagnosis of Alzheimer’s disease. But to put his research into perspective, you only need to consider that by 2040, it is predicted 81 million people will be affected by Alzheimer’s. Welcome to Up Close, Prof Ames.

DAVID AMES
Hello Jennifer.

JENNIFER COOK
Now let me begin by asking you just how many of the elderly are at risk of developing dementia?

DAVID AMES
Just to put this into context, dementia is a condition caused by a variety of brain diseases of which Alzheimer’s disease is by far the most common cause. And when we use the term ‘dementia’, it is really saying that somebody has had a decline in their mental functioning that has got to the point where it interferes with their ability to lead a normal life. So, someone with dementia is likely to be very forgetful. They’re likely to struggle driving their car, remembering to prepare dinner, paying their bills, remembering to lock the door at night, perhaps finding their way back home from the supermarket, that kind of thing. And, as most dementias tend to be progressive, you can go from the beginning stages of having mild forgetfulness through to in the more advanced stages a person may be completely unable to communicate or completely immobile, simply as a consequence of the diseases affecting them. Alzheimer’s disease is a degenerating brain disease where brain cells get disconnected and then die. And it probably accounts for anything from half to 80% of all dementia, depending a bit on how you define it and where you look for it. The other causes of dementia I should mention include small strokes affecting the brain, excessive use of alcohol, a few rarer conditions, such as frontal dementias, dementia with Lewy bodies, Huntington’s disease, but there is about 50-odd different causes of dementia known. Coming back to Alzheimer’s disease though, that is the most common cause, and if you’re aged between 60 and 65, you’ve got about one in a hundred chance of having a dementia. If you’re aged over 85, you’ve got something approaching a one in four chance of having a dementia. If you’re a hundred, there is over a 60% chance that you’ll be affected by a dementia, when you’ve reached that age. So, it is age related, but not every old person gets it and not everybody who gets to be elderly will get it before their lives are over. On the average, in a country like Australia, a woman can expect to have about 13 months of her life affected by a dementia, a man about 11 months, because men tend to live less long than women. But that is obviously made up of people who live for ten years and others who don’t have it at all.

JENNIFER COOK
Let’s look at this study that you’re undertaking into these risk factors for Alzheimer’s, what is it that you’re trying to achieve? You’re looking at things like lifestyle risk factors such as smoking, high blood pressure, obesity, but there’s also another couple of interesting factors you’re taking into account.

DAVID AMES
If we could just get everybody who is going to get Alzheimer’s to get it a bit later, there’d be tremendous cost savings to health systems and to social security systems, but also improvements in quality of life for people and their families. If we could get everyone who is going to get dementia, get it five years later that would halve the cost to society. And, Alzheimer’s disease is potentially a preventable or a delayable disorder. We’ve learnt an awful lot in the last twenty years. We’ve known about the changes in Alzheimer’s disease since Alzheimer looked down his microscope and then described what he saw in 1906. But since the early 1980s, researchers have come to understand Alzheimer’s disease much better. We know there are a cascade of events going on, that you’re body, which is made of proteins, proteins are the building blocks of your body, if you eat meat it is mainly protein, if you eat fish or eggs it is mainly protein. Proteins are the building blocks of your body, and there are thousands and thousands and thousands of different ones that your body is coded to make. It is pre-programmed to make them. And one protein that sits on the surface of cells and probably receives messages and passes them into cells, if it breaks down in a certain way, it forms a fragment, which is called a beta-amyloid and that fragment of proteins seems to start a cascade of destruction, which causes the connection between brain cells to inflame, then makes them disconnect and the connections die back and ultimately the brain cell itself dies. We are not entirely sure why some people get Alzheimer’s disease late in life and some don’t. There is a gene that makes you more likely to get it than somebody who hasn’t got that gene. But it is not the case that most cases are directly inherited, it is a risk factor gene, there is a tiny, tiny number of people who carry genes which cause massive increases in the amount of this protein that are made, but to put that in context, they’re about one in every hundred of people with Alzheimer’s disease. And in a country like Australia with 20-odd million people, there’s probably a hundred families who carry that gene at any given moment. So, most of Alzheimer’s disease, it is still a bit of a mystery why one person gets it at 65, somebody else gets it at 80, and why somebody gets it at 95. If we could pick up who was at risk of getting Alzheimer’s disease five or ten years down the track, and if we had drugs which could attack the formation of this protein or clear it out of the body, or try and prevent it being formed, then we would be in a position potentially, to wind back the age at which people got it. And, in parallel with what we are doing, there is a large amount of research going on to try and get what we call disease modifying drugs, that can actually either break down this protein by removing metals from it, or prevent its formation, by attacking the enzymes that create it, or, indeed by clearing it out of the body, for example, by immunising the body or giving the body anti-bodies to clear it out. So, if that parallel arm of research was successful in coming up with a treatment that not only could slow down the rate at which people with Alzheimer’s disease progressed, but prevent them getting symptoms when the disease was starting then you’d need to know who to apply it to. And our big aim, is really to try and find markers that can say ‘this person is going to get Alzheimer’s disease in the not too distant future. They haven’t currently got the clinical symptoms, but they’ve got the disease process already started.’ Just as your kidneys can be slowly deteriorating for a long time before you get kidney failure. Or your liver can be deteriorating for a long time before you get liver failure. You have to damage a lot of your brain before it stops working properly. But, we can, potentially, pick up who is actually going to get Alzheimer’s disease some years before the symptoms of the illness actually ever appear and that is the aim of the study I’m involved in.

JENNIFER COOK
And what has come up so far, is you’re looking at social connectedness and the role of education as well, tell us about that.

DAVID AMES
Okay, well, epidemiologists, that is people who go out into populations and ask them questions and try and see how much there is of certain things and what it is associated with, with illnesses like heart disease and cancers people have been pretty good at finding preventable factors, so you can tell people, ‘if you don’t smoke cigarettes, you can markedly decrease your risk of getting lung cancer, if you don’t eat a fatty diet, and if you don’t let yourself get overweight, and if you take a bit of exercise, then we can actually decrease the chances of you getting diabetes or other obesity related illnesses.’ With, what we call neuron-degenerative diseases, things like Alzheimer’s diseases, Parkinson’s disease, motor-neuron disease, multiple-sclerosis, we’ve been much worse, at finding preventable risk factors. We know with Alzheimer’s disease, the older you are, the bigger your chance of getting it, we know that if you carry this gene called APOE {epsilon} 4, that you have a three-times higher rate of getting Alzheimer’s disease in late life than someone who doesn’t carry it. But you can’t do much about your genetic inheritance. And you can’t do much about how old you are. What we are interested in, is to try and find preventable risk factors, and the only things that consistently come out of research in epidemiological studies, are things like, the number of years you’ve had in education, things like exposure to head injury, and those two things could work, in terms of what is sometimes called the ‘reserve hypothesis’. If you have education, presumably you connect up more brain cells, in fact you probably do connect up more brain cells. If Alzheimer’s is a disease that damages your functioning by disconnecting brain cells, if you’ve got more connections early on, then presumably you can disconnect more of them before you finally see symptoms. With head injury, if you damage your brain, but you’re still functioning and you start to get something like Alzheimer’s disease the symptoms may show up earlier, than they would have done if you hadn’t had that kind of problem. But what we are actually looking for is early diagnostic markers. Things that you can actually take a picture of, or do a blood test on, or get some other kind of test that can say, ‘gee Jen, you’re at risk of getting Alzheimer’s disease in ten year’s time because you’ve got this marker in you.’

JENNIFER COOK
That is really important, because if I have had a lot education, if I do have more of these connectors within the brain, perhaps I’d be better at covering up the early signs of Alzheimer’s. And also to, this issue of social connectedness, if I’m more able to talk to people, able to bluff my way through things, it can muddy the waters.

DAVID AMES
Absolutely. And one of the hardest things for a clinician, when they’re assessing someone who might have Alzheimer’s disease is, we’re used to seeing the average woman or man in the street and when we get a professor of linguistics or somebody who is highly educated, they tend to do better on the standard tests that we use and sometimes we have to pack them off to a neuro-psychologist for more detailed testing who actually look at predictors of their pre-morbid function and then say well, ‘this person is performing okay, for an average person, but are they actually markedly down as to how they would have been or used to be?’ You mention social connectedness, there is a couple of studies looking at what seems, apart from education, to be protective against the development of dementia in late life and it is always important with these things not to put the cart before the horse, in other words, you know, ‘are symptoms of depression causing Alzheimer’s disease or are they early symptoms of somebody withdrawing because they’re not functioning? Is somebody stopping playing golf, or stopping cooking, or stopping getting active with their friends and doing things – is that an early symptom of Alzheimer’s disease or is that something that is a risk factor for it?’ What tends to be important, as far as we can tell, is the maintenance of meaningful activity. So, sitting around, doing nothing probably isn’t good. But, if you’re doing something that has meaning to you, whether that is gardening, or learning German, or listening to music, or playing with your grandchildren, or cooking for the whole family, whatever it is, if it has meaning for you, then there is the possibility, that to some extent it is protective.

JENNIFER COOK
That is fascinating. That your passions could somehow immunise you.

DAVID AMES
It’s good to know that using your brain won’t wear it out.

JENNIFER COOK
It is very comforting.

DAVID AMES
It is also, a lot of things we do in medicine, we make recommendations to people and there is an old Latin saying, that goes back to the early history of medicine, which is ‘first, do no harm’. So, if you are going to make a recommendation and it turns out to be wrong, well you better be hopeful that it is not a damaging recommendation. I think, by telling people to be connected, and be active and to keep engaged, we are unlikely to be doing anything that is going to be doing them any harm. Because there is evidence that those sort of attributes also are associated with lower rates of depression and higher expressions of qualities of life and life satisfaction. But we think that keeping your brain active may possibly help a little bit to protect it against Alzheimer’s disease, but it is not a perfect protection. I see people who have had academic careers who get Alzheimer’s disease. I see people who have been extremely active and extremely connected to all sorts of things who get Alzheimer’s disease. We’re talking about possibly pushing things back or reducing your risk. But what we really need to do, as I said earlier, is to try and be able to pick up who is at heightened risk and if we had interventions that we could apply in order to be able to apply them.

JENNIFER COOK
I’m Jennifer Cook and you’re listening to Melbourne University Up Close and my guest today is Prof. David Ames, who specialises in the early diagnosis of Alzheimer’s disease. Prof Ames, the question of whether or not there is gender differences that need to be taken into account when you do look at Alzheimer’s, taking into account that issue of social connectedness, now an instinctual response would be for me, is that women are better at those social connectors, with their family and out in the community – it’s a generalisation – but when you look at the research, women, and you said yourself, seem to be at a higher risk of getting Alzheimer’s, so, how does gender come into play?

DAVID AMES
Alzheimer’s disease is fundamentally an aged related disorder as we discussed earlier. Women – it is either a curse or a blessing, depending on how you look at it – but women live longer than men. So, there is more women around in the age group that can get Alzheimer’s disease, than there are men. The other issue is, once they’ve got Alzheimer’s disease, they again, live longer than men. So men, who have got Alzheimer’s disease are more likely to die sooner because they’re men and they have higher rates of heart disease and various other things than women who have got Alzheimer’s disease. So, two reasons, one is there is more women in the age group, second, there is more women who get it, live longer. There has been some signal in some studies that suggest that even if you take those things into account women may still be getting Alzheimer’s disease at an excessive rate. That is still slightly controversial. Some of the stuff that has been put forward has been to suggest that maybe men go on secreting sex hormones, testosterone into old age, whereas for women, they tend to turn off into middle adult life. But that has got a lot of flaws in it that theory, because some of the estrogen replacement studies haven’t really shown in studies where they have actually been applied and people who have been tested and followed up, haven’t shown clear rates in dementia reduction. And so, it is still a little bit controversial that area, but the important thing is that Alzheimer’s disease is mainly a disease of women simply because they’re the ones who live into the age groups in large numbers where you get it.

JENNIFER COOK
Let’s take our focus a little wider now, we’ve spoken about the personal challenges facing someone with dementia – the memory loss, the loss in function, but for many people it is fate worse than death, I’ve heard it described as. But let’s extrapolate that out to with a growing aging population, what does this mean for society and for cultures, with more elderly people who need care?

DAVID AMES
I will talk about that. Just this business about ‘a fate worse than death’, there used to be a billboard poster at the Australian Alzheimer’s Association had a few years ago, which showed an old lady and a family, and two parts of a photograph, and the billboard said: ‘she’s got dementia, and they all suffer from it.’ The implication being that the family member through the nature of their illness, required care and assistance it was upsetting to people because the person they loved was no longer functioning as they were. And it is very variable as to how much people with Alzheimer’s appear to suffer. Some of them are bothered, by their memory impairment. But you know, if you believe in a divine entity you might say that one of the merciful things about the creation of Alzheimer’s disease is that at the same time, the capacity to worry about it is diminished. People with Alzheimer’s disease often lack insight into the nature of their problem. The frontal lobes of your brain, the parts that tell you how you are going, the parts that give you feedback on how you are functioning, actually get damaged in Alzheimer’s disease and some people with Alzheimer’s disease are relatively unaware of the fact that they’re not performing well, or that something is wrong with them. It isn’t universal. Some people with Alzheimer’s disease are very anxious. It is a bit like being in a Kafka novel, constantly waking up wondering what the heck is going on because nobody has told you why the things around you are happening. And that can make people anxious. But others have an aura of blithe unconcern. So, yes, some people with Alzheimer’s disease suffer, but so do people with a lot of other illnesses. Not everybody with Alzheimer’s disease appears to be suffering so far as we can tell. Now, coming back to what this means for society is, we’ve never had as many people alive as we’ve got today, we’ve never had as many old people alive as we’ve got today in the world, and we’ve never had as many old people as a percentage of the total population as we’ve got today. Now, this, if you like, is one of the consequences of the success that we’ve had in that making sure, by and large, peoples’ children don’t die of water born diseases in infancy, that epidemic diseases such as scarlet fever or measles or influenza don’t wipe out large numbers of people. We have probably, compared to some earlier parts of the century, although this is a bit of an issue in different parts of the world, diminished the number of people dying in wars. Certainly, for example, Western Europe hasn’t had a major war since 1945, but they managed to clean up a fair few people in that one. So, it is a penalty of success, really, that you’ve got more people living to be elderly and if something else doesn’t get you, eventually the age related diseases will. One very good example of this, in terms of the change in demographic structure, is China, whereby the middle of the century, a third of the Chinese population is going to be aged over 60. That is because they have artificially reduced their birthrate with the one child policy to deal with their massive overpopulation problem.

JENNIFER COOK
That is a huge cultural shift.

DAVID AMES
So, there’s a huge bulge, if you like, of people moving through the Chinese population, and instead of having a pyramid, they’ve got this slightly diamond shaped population structure. I think it is hard to foresee exactly how the demographic change moving to more and more older people is going to be affecting different cultures and it probably will affect different cultures in different ways. North Asian cultures in particular have a tradition of veneration for older people, which I think is a good tradition, but whether that will actually hold up, you know, in 10, 20, 30 years time is a difficult thing to say. I think the other major cultural changes have to do with the cohorts that go through. Different cohorts have different expectations. The baby boomer cohort, the people born in America and Western Europe and Eastern Europe too, after 1945, up until about 1955, they start turning 65 in a couple of years. And we know that childcare was revolutionised, child upbringing was revolutionised with the post-war ideas of Dr.Spock and everybody else. That generation was the one that drove the summer of love and the discontent at universities in the 60s. It is a generation that has certainly re-invented issues like relationships between work and family and how people live their lives and I think it is hard to foresee exactly how they’re going to behave when they get into an older age group.

JENNIFER COOK
Not quietly, would be my guess.

DAVID AMES
Exactly. They’re not the sort of people who are going to go quietly into that good night. They’re the people that are actually going to, as a generalisation, they’re going to certainly shake, rattle and roll. And you’ll hear about it, whatever it is they think. So, my suspicion is that that is going to become, certainly in countries like Australia or Britain or Western Europe or North America, it is going to be a major cultural issue. I think we can’t tell until some of it has happened how it is going to play out.

JENNIFER COOK
And getting back to what you said about China, I just had this stark image of only children, caring for elderly grandparents.

DAVID AMES
Well, it is one thing, isn’t it, to care for your grandparents, if there is eight of you, it is another thing to care for four grandparents if there is two of you. And the same goes for parents. You spoke of cultural issues, I’ve always said, the thing that you want to do, if you want to be looked after in your old age is to have two daughters. Because daughters generally take more care of their parents than sons do, and daughters who are only children are terrific at caring for mum, in my experience, but it is probably a good idea to have a second one as an insurance policy.

JENNIFER COOK
Well, David, I only have one daughter; I’ll have to -

DAVID AMES
If there is half a dozen of them, it often seems to me, that culturally, in clinical situations, the ball gets shoved around or one kind of gets elected and – I saw somebody the other day who was doing, she was one of five, but she was doing 95% of the caring for her mum. Partly because mum had alienated the affections of the other four, but also I think because she just, in some ways, had a more dutiful or other attitude to the whole issue. But there are very interesting relationships within families that determine who does the looking after if anybody does, and if they go somewhere, who visits and when they come and see people.

JENNIFER COOK
Prof Ames, many thanks for joining us today.

DAVID AMES
Thanks for having me.

JENNIFER COOK
I’m Jennifer Cook and my guest at Melbourne University Up Close has been Prof David Ames, the director of the National Aging Research Institute at Melbourne University. Melbourne University Up Close is brought to you by the Marketing and Communications Division, in association with the with the Asia Institute of the University of Melbourne, Australia. Relevant links, a full transcript, and more information on this episode can be found at our website at upclose.unimelb.edu.au. We also invite you to leave your comments or any feedback you’ve got on this or any other episode of Up Close, just click on the ‘add new comment’ link at the bottom of the episode page. This program was produced by Kelvin Param, Eric van Bemmel and myself, Jennifer Cook. Audio recording is by Craig McArthur, and the theme music is performed by Sergio Ercole. Melbourne University Up Close is created by Eric van Bemmel and Kelvin Param. Until next time, thanks for joining us.

VOICEOVER
You’ve been listening to Melbourne University UpClose, a fortnightly podcast of research, personalities and cultural offerings of the University of Melbourne, Australia. UpClose is available on the web at upclose.unimelb.edu.au, that’s upclose.u-n-i-m-e-l-b.edu.au. Copyright 2008 University of Melbourne.


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