Forgetful or early-stage dementia?

Anthony White: 
Thank you.

Clare Blake: 
Let’s start with how a normal memory works.

Anthony White: 
Yeah, so with normal memories, you have brain cells called neurons and they interact with each other through connections called synapses and you have billions of these interactions. And when you have a memory, it includes a whole range of cells throughout the brain that link together and form your memory through their interactions with each other. When you recall a memory, there’s release of chemicals and electrical signals in the brain that stimulate these connections, and then you get the memory forming and released back into your mind.

Clare Blake: 
And that deteriorates with age. Is that normal?

Anthony White: 
Yeah. So that’s quite normal from about sometime in your forties – the connections between these brain cells and neurons start to break down a little bit. It’s sort of a little bit like the electrical wiring that might sort of corrode with time. You start to lose these connections, and then you lose the interaction with a memory formation. That’s a perfectly normal process from around about your forties and fifties onwards.

Clare Blake:
What is the difference between dementia and Alzheimer’s?

Anthony White:
That’s a good question. Dementia is really the loss of your memories that occurs in a disease such as Alzheimer’s. When you get dementia, it can be a part of other diseases. So you can have a disease called frontotemporal dementia, which affects a different part of the brain, or with motor neuron disease or Parkinson’s disease. So you can get dementia without having Alzheimer’s disease, but if you’d have Alzheimer’s disease, then you will have dementia. So you will lose the memories, but Alzheimer’s disease also involves a number of other changes in your brain in terms of the way that you learn and can do other things with your brain and so on. If you have Alzheimer’s disease, dementia is part of that. And the two words are kind of interchangeable now.

Clare Blake:
You’d be forgiven for thinking this is more common now. Is that the truth?

Anthony White:
Yes, it is. It’s very common. There’s about 400 000 people in Australia with dementia or Alzheimer’s disease now. That may increase to about a million people by 2050. Over the age of 65, it’s about one in 15 people have dementia or Alzheimer’s disease. And over the age of 80 there’s about one in six. So it becomes quite common in people at very old age.

Clare Blake: 
So it’s not just better diagnosed now, it’s actually more common?

Anthony White:
It is becoming a very common problem in older people.

Clare Blake: 
So I imagine that’s a big part of your work, finding out why?

Anthony White: 
Yeah. So we’re trying to understand what causes Alzheimer’s disease, why it affects some people and not others and then trying to understand the ways that we might be able to treat it.

Clare Blake: 
There’s a lot of myths around, Tony, about the causes. Could we bust a few here?

Anthony White: 
Yes. One of the most common myths I think is that you can get Alzheimer’s disease from aluminium saucepans and cooking material. Also from amalgam in your fillings, from vaccines and so on. None of these things will cause Alzheimer’s disease. They have no role at all in causing disease. There’s also myths around the fact that Alzheimer’s only involves memory loss, but it also will lead eventually to people dying from the disease. People tend to think that there may be cures out there for Alzheimer’s, but there’s no cures at the moment. We can talk about that a little bit more later.

Clare Blake: 
A big misunderstanding too – memory loss is just one of many symptoms. What are some of the others?

Anthony White: 
With Alzheimer’s disease it’s really about the way it affects your entire brain function. So your ability to learn new things and to be able to do all the sort of tasks that you used to be able to do, they can deteriorate. So it’s not just the memory loss, it’s everything that you can do with your brain eventually will be affected.

Clare Blake: 
And anyone caring for someone will know that some people deteriorate quite quickly and others more slowly.

Anthony White: 
Yes. It’s a disease that people say that if you’ve seen one person with dementia, then you’ve only seen one person with dementia. Everybody is very different with the disease process. And that’s related to a whole lot of different factors on how the disease affects people. And this is something we’re starting to understand in terms of trying to treat people with Alzheimer’s disease. That because everybody’s different, we need to be able to treat them differently as well.

Clare Blake: 
We don’t really understand what’s causing it. Do we have an insight to the risk factors?

Anthony White: 
Yes. There are a number of risk factors that are known for the disease and some are what we call modifiable risk factors. If you have adult onset diabetes, high blood pressure, smoking, lack of physical activity, if you’re obese, also even exposure to things like air pollution – we believe that these things can affect the likelihood of being able to get Alzheimer’s disease. There’s also what we call non-modifiable factors. So these are the genes that you’re born with and you can’t obviously change that. And there’s a whole range of genes, such as, one is called the Apolipoprotein E. If you have one form called the APOE e4, you have a very high chance of getting Alzheimer’s. If you have APOE e3, you have a lower chance of getting it. But it doesn’t mean that you will get the disease, it just means that your chances are greater. So whether you get the disease depends on a whole range of interactions between the modifiable and non-modifiable disease factors to determine whether you’re actually going to get it.

Clare Blake: 
I guess both of those contribute to the fact that some people get it very young.

Anthony White:
That’s right, yeah. So the disease can occur very early on. Actually, there are some mutations that will cause the disease to occur in people even as young as 30. But most people won’t get it until after 65 and more likely 70 or 80. It’s due to a whole range of factors and even if you do everything right and you do your physical activity and you look after your weight and you don’t have diabetes and all these kinds of things, you may still get Alzheimer’s disease. And consequently, there are people who have all the risk factors and still don’t get the disease. So we don’t know exactly what causes it from one individual to the next, it’s just a whole range of risks that we can identify.

Clare Blake:
Which makes it such a frightening disease, doesn’t it?

Anthony White: 
It is. It’s very difficult to predict who is going to get it and over what time course and how to treat those people.

Clare Blake: 
I know from seeing you speak a number of times, somebody in the audience always says, “I just walked into a room and I forgot why I was there. Should I be concerned?”

Anthony White:
Yes. I wouldn’t be concerned unless it’s something that you’re doing a lot. As we age, as I mentioned, your connections between your brain cells start to break down a little bit and losing your normal short-term memory is something that just happens with age. It’s kind of like the brain isn’t functioning at its peak performance anymore. But it’s more about if you start to do things that are very unusual and something that you’ve never done before, that’s really something to take notice of. For example, you may have a recipe where you’ve cooked a meal for many, many years of your life, and suddenly you just don’t know how to do it anymore. Or you might get in your car when you’re at a shopping centre and you don’t know how to get home. You might start putting things around the house in very unusual places that they’ve never been before. Things like that, the things that just really stand out as something that’s just very unusual. And that could be an indication of dementia, but of course, it could also be other problems as well. So you need to check with your doctor, because it could be other reasons that are causing these kinds of changes.

Clare Blake: 
Stress is one of those, isn’t it?

Anthony White: 
Yes. Stress, combinations of drugs sometimes do it. Other illnesses can cause it. So because you have these changes, it doesn’t mean that you have dementia, but it will need to be checked out by your doctor.

Clare Blake:
And if you forget people’s names, then you don’t need to worry because that’s very…

Anthony White: 
It is very common, particularly if you’ve just met somebody or you’ve only known them for a short time, we all forget people’s names. If you forget the name of somebody in your immediate family, that obviously is something is very different. So it’s again, it’s something that’s really out of the ordinary. Just very simple memory loss about various things like where you put your car keys and sunglasses and so on, that’s not something to be concerned about.

Clare Blake:
Phew. Well, you only need to do a quick search on Google and find plenty of potions claiming to treat dementia and Alzheimer’s. Where do you sit on that, Tony?

Anthony White: 
Yes. Unfortunately at the moment, there are no treatments that will cure Alzheimer’s disease, but there are a lot of people who will say that they have something that can cure you or stop the disease or ‘I got better from dementia’. If people do get better from dementia then they probably didn’t have it in the first place, it might’ve been a misdiagnosis. You have to be careful about what the ulterior motive is of people who are offering these things. If they’re making money out of it directly, then clearly that’s a business opportunity for them. And unfortunately people do try to cash in on people with dementia and offer them something that isn’t really going to do anything for them. Medical doctors don’t get paid to give you a particular drug, they just get paid to treat people with the disease. So they will treat you with the drugs – they’re all prescription drugs – that can modify some of the symptoms that you have. But if there was a treatment for Alzheimer’s disease that actually stopped it, it would be so well known by everybody. It would be across all the major news outlets, not hidden away on a website somewhere.

Clare Blake:
So you could probably go into a pharmacy and disregard most of the vitamins that are going to help you with memory loss and dementia and Alzheimer’s or support…

Anthony White: 
That’s right. For most of the supplements, despite what they claim, they will only be any use to you if you are deficient in some kind of vitamin or mineral, and your doctor can do a blood test and tell you if you’re deficient in something and whether you need treatment with some kind of supplement. If not, then these won’t do you any benefit at all, and in fact, taking too many of them can be detrimental and can actually cause you harm.

Clare Blake: 
That’s a good point to raise and the information we’re giving you here is general. It’s not personalised medical advice. Your doctor is always the best person for that.

Anthony White: 
That’s right.

Clare Blake: 
And we have spent a huge amount of effort, time and money on developing treatments for [dementia and Alzheimer’s disease]. Why has nothing worked so far?

Anthony White: 
Yes, that’s a very good question. And we have spent a very long time, several decades, trying to understand the disease and treating it, and it really hasn’t worked out. And I think there are two major issues that have come up. One is that the disease is much more complex than what we originally thought it was. And the other is the fact that people are very different and the disease occurs differently in everybody and we need to treat people differently. And also, the fact that the disease seems to occur over many decades and a lot of disease occurs before we actually see symptoms in people and we need to try and understand when it’s occurring and be able to treat people much earlier. We understand these things now, and we think that we can probably make some kind of gain in treating people with being able to identify how to treat people earlier and treating individuals.

Clare Blake: 
How do we find them if they’re asymptomatic?

Anthony White: 
That’s a good question and it’s very difficult. So, we can detect people at a much earlier stage from the very small changes in their behaviour. So rather than just having major changes in memory loss and so on, we are able to now detect changes in the way people’s eyes might move towards a particular object or the way that they can smell things and so on. All these kinds of changes occur within the brain at a very subtle level, very early on in the disease.

Clare Blake:
Say you find it really, really early on, what are your chances then with the current medications we have of staving it off a little longer?

Anthony White:
Well, as I said, there’s no drug at the moment that will stop the disease, but there are some things that you can do to slow down the process. It’s very important to stay in social contact with all your friends and family and so on. Also, just being able to use your brain a lot, trying to learn new things, trying to do things like maybe learn a new language or sudoku or dancing or something – something that really makes your brain work to learn something new. It’s kind of like muscles, if you don’t use them, they’ll start to deteriorate. And your brain is a little bit the same. So you need to be able to use it all the time. And that can slow it down a little bit.

Clare Blake: 
Your research group here at QIMR Berghofer is making miniature brains. This is unbelievable work. They’re actually in Petri dishes. Can you tell us a little about these miniature brains?

Anthony White: 
Yes it’s very exciting work. The mini-brains, or organoids as they’re called, are just small pieces of brain tissue that grow by themselves and it enables us to understand the more complex changes that are occurring in Alzheimer’s disease or dementia. Traditionally, we were only able to look at single cell types in very short timeframes. Now we can look at how the cells grow over very long periods in a very complex environment. And obviously that is a much better model of what’s happening in the brain and therefore being able to look at the changes that occur during Alzheimer’s disease and trying to find new treatments for that.

Clare Blake: 
So instead of treating the person, you can treat the little brain in the Petri dish and see how it responds?

Anthony White: 
That’s right, yes.

Clare Blake: 
Where do you get these little pieces of tissue?

Anthony White: 
So, it’s taken a long time for various groups around the world to identify the conditions to grow these mini-brains in a Petri dish. But now we understand there’s a range of chemicals that we can add to stem cells, which can grow into lots of different cell types of the brain. And once you start growing them, the genes that the cells have can actually direct the cell to grow into the right type of brain cells and organise themselves just as they do in the brain. It’s all pre-programmed into the cells. And then once you add the chemicals, they just grow into these brain-like structures.

Clare Blake: They actually look like tiny little brains. They’re about half the size of a thumbnail.

Anthony White: 
Yes, they’re a few millimetres across and they do look like mini-brains, but they’re not actually a brain shrunk down to a small size. They’re more like a piece of your brain that if you took a piece out of your brain and looked at it, you’d see this organisation of cells that form what’s occurring in your brain. We are getting better at growing larger organoids now, or mini-brains, and they will continue to get bigger as the techniques are developed over time.

Clare Blake: 
Did it have any brain waves? How long do they live?

Anthony White: 
They do have brainwave. And in fact, some recent studies have shown that they do have the formation of brainwaves very similar to brains in a developing human. We can actually grow them for a year or two in these Petri dishes and that may increase as we get a better understanding of how to maintain them.

Clare Blake:
It’s such extraordinary research and it seems like this is a great hope for the future. What are you hoping to get from the tiny brains in terms of, going forward?

Anthony White:
Well, we’re trying to identify ways of stopping the process of memory loss in the brain. That’s really due to the, I mentioned earlier, the way that the brain cells interact across a broad region of the brain. And traditionally, we’ve only been able to look at the way that cells interact in a very small area and just one type of cell. And now we can look at the way a whole lot of different cells interact over a much larger area – and that’s a better model of what’s happening in the human brain – and be able to apply drugs to that, to try and improve the interactions between the cells and stop the loss of the memories.

Clare Blake:
And how are you going in this study so far?

Anthony White: 
It’s very good. So, we’re able to grow the cells of the mini-brains really well and understand what’s happening between the cells and look at the whole interaction between a whole lot of different cells. I think generally across the whole field, there’s a lot of optimism now that we could have treatments for Alzheimer’s disease within the next few years, particularly as it’s all coming together in terms of identifying people much earlier on in their disease, just as with cancer. Once upon a time, it was difficult to treat people with cancer because you identify them too late and the drugs weren’t very good. But now, the treatments are quite good, particularly if you can detect the disease early. And the same thing will happen with Alzheimer’s. If we can detect people early and treat them early with lots of different drugs for different people, then we’ll have a much better impact on the disease.

Clare Blake: 
So if you have someone in your family with dementia, Alzheimer’s, you can go and get a genetic test and find out if you have these genes?

Anthony White: 
There are some genes that you can be tested for, and they will tell you whether you have increased likelihood of the disease. Again, even that means that you won’t necessarily get the disease. And if you don’t have the genes, you may still get the disease. So at the moment, there may not be a lot of help in doing that. If there’s a mutation in your family, you probably will already know about it because they’re very rare, but they occur in particular families and people die of the disease at a very young age. So if you don’t have that in your family, it’s probably not there and you’ll just have the normal risk of anybody has for Alzheimer’s disease. It may help if you do have a high-risk gene, maybe there are things that you might want to do to try and reduce your decay of your brain over time, if you’re likely to get it. But again, you may not get it at all.

Clare Blake: 
And there are some types of dementia and Alzheimer’s that you know are more heritable.

Anthony White: 
Yes, that’s right. So again, some people will come from families where you have a very high chance of getting it because someone else in your family has got it. And that’s one of the predictors is if people in your family have Alzheimer’s, then you are a higher risk of getting it. But again, it doesn’t mean that you will get it.

Clare Blake:
Does it have different names?

Anthony White: 
Yes. So we’re trying to understand now the different types of Alzheimer’s disease and dementia. And in fact, there’s been a new form identified in the last couple of years to really help us to understand that there are a whole range of different forms of Alzheimer’s disease and they affect people slightly differently. And this is helping us to understand the disease process and also how to target drugs to different people for their different sub-form, if you like, of Alzheimer’s disease,

Clare Blake: 
Do you mind Tony if I ask you how you became so passionate about this disease?

Anthony White: 
Well, I was always very interested in the brain from a young age. It’s a very misunderstood organ. There’s not a lot we know about it. And the more we delve into it, the more we find fascinating things about it. And so I was working on the brain from a very early stage of my career. Then unfortunately, my own mother got Alzheimer’s disease and she passed away a few years ago from the disease. And that obviously made me more determined to try and understand not only disease causes, but try and find ways of treating disease, given that there was really nothing that we could do at the time.

Clare Blake: 
Tony, it’s heartening to have you on your team and your tiny brains on the case. I hope that something happens in the future with your work.

Anthony White: 
Oh, thank you. Yes. I think it’s a positive time that even though there’s been quite a lot of failures in terms of drugs, that we’re at a point now where that may change over the next few years and we’ll see some kind of balances with treatments for Alzheimer’s disease that will make a difference.

Clare Blake: 
And if you’re interested in following Associate Professor Anthony White’s unbelievable work, or any of our research, go to qimrberghofer.edu.au. Thank you Tony, it’s been fascinating.

Anthony White: 
Thank you very much.