The Future Of

Alzheimer's | Prof John Mamo & Dr Virginie Lam

Episode Summary

Curtin researchers are trialling a medication that could help preserve the cognitive function of people with Alzheimer’s.

Episode Notes

Curtin researchers are trialling a medication that could help preserve the cognitive function of people with Alzheimer’s. 

In this episode, Sarah Taillier is joined by Professor John Mamo and Dr Virginie Lam from the Curtin Health and Innovation Research Institute. They discuss how they’re trialling an existing drug that could be a game changer for people with Alzheimer’s by preventing the build-up of a protein called amyloid beta in the brain. They also explore some of the lifestyle factors that are likely to cause the disease. 

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Professor John Mamo

Professor Mamo is a John Curtin Distinguished Professor and Director of the Curtin Health Innovation Research Institute (CHIRI). He leads a team of physiologists and vascular biologists in exploring cerebral capillary dysfunction in a range of neurodegenerative diseases including Alzheimer's, multiple sclerosis and in pain disorders. 

John is the Principal Investigator of a nationally funded drug study in Alzheimer’s disease. He has published 200 peer reviewed publications and been cited on more than 6300 occasions.

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Dr Virginie Lam

Dr Virginie Lam is an Early Career Research Fellow with preclinical and clinical expertise investigating the role of micro-nutrients in regulating brain capillaries and cognitive performance. Her research is funded by the National Health and Medical Research Council.

She completed her PhD in 2016 and currently possesses authorship to more than 60 publications.

Virginie’s current line of research examines the interactive effects of vasoactive nutrients with lifestyle and pharmacological interventions that can restore vascular damage to improve cognitive health and halt the onset and progression of vascular-based neurodegenerative diseases.

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Transcript

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Team

Host: Sarah Taillier

Content creator: Zoe Taylor

Producer and recordist: Emilia Jolakoska

First Nations Acknowledgement

Curtin University acknowledges the traditional owners of the land on which Curtin Perth is located, the Whadjuk people of the Nyungar Nation, and on Curtin Kalgoorlie, the Wongutha people of the North-Eastern Goldfields; and the First Nations peoples on all Curtin locations.

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Episode Transcription

Sarah Taillier: 00:00 This is The Future Of, where experts share their vision of the future and how their work is helping shape it for the better. I'm Sarah Taillier. Dementia is a loss of cognitive function and the World Health Organization states that more than 55 million people currently live with dementia worldwide. Alzheimer's is the most common form of dementia. It affects a person's memory, language, and problem solving and thinking abilities severely impacting their quality of life. There is currently no cure for Alzheimer's, but a breakthrough drug developed by a team at Curtin University could drastically slow the progression of the disease.

00:43 To explore this topic, I was joined by Professor John Mamo and Professor Virginie Lam from the Curtin Health and Innovation Research Institute. If you'd like to find out more about this research, you can visit the links provided in the show notes.

00:57 John, you were on the podcast in 2019 to talk about Alzheimer's disease, but since then you and your team have been very busy developing further research into a toxic protein called amyloid beta and its potential linked to Alzheimer's. Can you tell us about what you've found?

John Mamo: 01:16 Yeah, thanks very much. Yeah, we had a hypothesis that really commenced about 10 years ago, and it was along the lines that what might lead to the trigger for Alzheimer's disease might be corruption of microscopic vessels in the brain called capillaries. These are the smallest of blood vessels. You can't see them with the naked eye. And what our early lines of research inquiry suggested was that there was something occurring outside of the brain, something being secreted into blood, which compromised those microscopic vessels. And then there was leaky too carrying into the brain and this caused some inflammation and the brain cells began to die. The breakthrough discovery, which really was only realised in 2021, where we published a really substantial paper was about eight years ago, we had deliberately wanted to test the hypothesis in the most robust way possible, and that was to genetically engineer some mice, make them human-like in some ways to see whether this pathway that Alzheimer's might occur from outside of the brain was actually just a crazy idea or one which really had some relevance to it.

02:26 And the gist of the findings were as follows. So probably a number of your listeners would know that in Alzheimer's disease, it's characterised by the accumulation of protein in the brain called amyloid beta. And if that protein persists in brain, it can compromise the viability of brain cells. They'll die, you'll get silent inflammation and cognitive loss occurs later on in life. Our hypothesis was, and the discovery was that amyloid beta is also made outside of the brain and it's actually secreted as a primary physiological function, which is to regulate how fats are metabolised. So all of us get our LDL (low-density lipoprotein) cholesterol level measured periodically, and LDL is one of these complexes in blood which transport lipids in the aqueous environment of the blood and amyloid is one of the proteins which tells those lipids where to go to. And the gist of our discovery was that if one produces too much amyloid over too long a period of time, it will progressively compromise the integrity of those brain capillaries and the whole lipoprotein, the lipid, the fat amyloid complex leaks into the brain and that's what causes the inflammation.

03:49 Now the exciting thing about that is twofold. One is that if this is really a pathway for Alzheimer's disease, then we've got a target to identify and develop prevention strategies. And we've done a lot of work which says that we know components of the diet can influence how much of the fat amyloid you have in blood. We know that certain metabolic conditions such as diabetes could also play a role. So we've got some ways of reducing it just like we reduce cardiovascular disease with various interventions. But it also provides us some opportunities potentially for treatment. And one of the major lines of research inquiry that Virginie and the others in the team and I have been pursuing is we've identified a drug that was used many, many years ago to reduce cardiovascular disease risk, which has a really profound effect on how much of this fat amyloid is being secreted into blood.

04:50 And in the studies which led to a clinical trial which we launched last year, those studies found in our animal models that if you suppress the amount of lipoprotein amyloid in blood, you'll preserve the brain capillaries. You won't get leakage into the brain and the brain cells remain healthy, and cognitive function is kept constant. So that's really exciting because it's a historic drug that was used clinically. We already know quite a bit about it. We know it's safety and tolerability and we were fortunate to have a really good team of leading discipline physiologists and medical people, and we were able to secure some funding through the Medical Research Future Fund to launch a clinical trial commencing initially in Perth looking at people with early Alzheimer's and whether this strategy's got to be effective in supporting cognitive function.

Sarah Taillier: 05:47 So you've been mentioning we a couple of times, we’re going to welcome Virginie in. Virginie, when you're talking about those clinical trials, Virginie, you and the team have began those trials of the drug probucol, which John has been pointing to. The trial will test whether probucol can prevent amyloid beta from leaking into the bloodstream and into the brain. Can you tell me more about how probucol works? You've touched on it a bit there, John, but also what do you hope to discover from this trial?

Virginie Lam: 06:15 Yeah, sure. Well, thanks for having me on here today. So yeah, like John covered before, Alzheimer's disease is a very multifaceted disease. So you've got breakdown of brain capillary, so the tiny vessels that essentially protect you from the peripheral metabolism from the brain as well as inflammation and oxidative stress. So what is really important is to identify an intervention that can actually target all three of these mechanisms, as well as other mechanisms as well. So what probucol actually does, we call it the wonder drug, but essentially it's able to target a number of these mechanisms more or less at the same time. So we've shown in our animal model studies, is able to reduce inflammation in the brain, is able to protect the vasculature, so the brain capillaries and all in all, it can actually support cognitive function in these animal models of Alzheimer's disease as we've worked with.

07:09 So we're actually the only team in the world that we're aware of that's using probucol for this indication for Alzheimer's disease. So at the end of this two year randomised control trial, we're hoping to see stabilisation of cognitive performance. So we're hoping to see less degenerative changes seen in the brain. So yeah, that's what we've been working on for the last couple of years and we're hoping this transpires to helping. There's millions of people that have dementia right now and that's expected to keep growing unless we find a preventative cure.

Sarah Taillier: 07:43 And so if that is the case, if probucol is found to stabilise cognitive performance with early Alzheimer's, what could be the impact of that? How significant is it?

Virginie Lam: 07:56 Well, the impact can potentially be huge. Probucol has been historically used as a lipid lowering drug, so the safety and the tolerability of the drug is very, very well characterised already. So you can not necessarily skip a lot of the phase one trials required to get a drug through, but a lot of it is understood about how the drug works. So yeah, I think what we hope to find by the end of the trial is that we can prevent or stop the Alzheimer's process from getting worse.

Sarah Taillier: 08:31 And Virginie, you mentioned that there are millions of people that are affected already. The World Health Organization predicts that 139 million people will be living with dementia by 2050, and for context, it's estimated more than 55 million people are living with dementia right now, with Alzheimer's being the most common form of dementia. What are some of the reasons behind that really high forecast?

Virginie Lam: 08:59 Couple of things. So with the global age increasing rapidly and population increasing rapidly as well. So you've got more and more people in the age bracket that are at greater risk of developing dementia. And like you said, the most common form of dementia is Alzheimer's disease. So there's a lot of risk factors that can be modified through lifestyle and environmental factors as well. So obviously some genetic factors do increase risk of people getting Alzheimer's disease, but there are certainly lifestyle factors that we can all control. So for instance, vascular risk factors and there's also obesity as well and stroke with the cardio cardiovascular heart disease as well. So yeah, it's really controlling these risk factors, whether it's controlling eating of dietary patterns, whether it's behavioural changes, sedentary lifestyle. So there's a lot in that, particularly with dietary factors, adaptation of Western style diet. So there's a lot of people that aren't looking after their diet, so that's one of the things that we can definitely just work on initially. Yeah.

Sarah Taillier: 10:13 John, what are some of the current treatment options for people that who are living with Alzheimer's?

John Mamo: 10:19 So unfortunately not real good in my opinion. Now, there has been a lot of hype in very recent times, so if I can explain to you the various class of drugs and how they essentially work. So there's a couple of drug strategies which are there to treat people who have cognitive impairment. One essentially is to try and support the crosstalk between brain cells to get them to communicate better. Usually people who take those class of drugs will get... Only some will benefit for a short period of time and it won't be sustained. Then there's another class of drugs which target a particular toxic component, which tends to build up not amyloid, it's a different component. And similarly to the other drug which supports communication between cells, some people will benefit for a short amount of time. The last 12 or 18 months, there's been a lot of media attention about a new class of drugs which have been designed to chisel away at that accumulation of protein.

11:25 This amyloid protein which occurs in the brain, which is thought to cause the disease process. There's a lot of trouble initially developing those drugs safely for human use. But the latest studies have shown that these drugs are very effective at reducing the amount of plaque material which is accumulated in brain. And just at the end of last year at probably the world's biggest stage for clinical trials in Alzheimer's disease, which was held in San Francisco, a lot of attention on a new drug called lecanemab. So this is one of these therapies that chisel away at this toxic plaque protein. The controversy in my opinion, and many in the area are really quite concerned about is that it was undeniable that the drugs effectively reduced the amount of amyloid accumulation in brain. However, when you actually took a look at the effect it had on cognition, either memory and the behaviour and so forth, there was no difference between people who were randomised to the placebo control.

12:36 So the best readout I think you can get from these later studies is that they've developed a strategy to potentially change the pathological course of the disease, but at the moment, they're not sufficiently effective to have any real impact on the person living with the disease. Now the reason many are concerned about this is these interventions are, A, hugely costly, we're talking like $55,000 US per annum. They require intravenous injections with about one in five people having a serious adverse event to that. So you have to weigh up if you want to go down that course of intervention, whether what's the benefit to the person living with the disease? And that's arguable. The precursor drug prior to lecanemab, which was approved early last year, probably in the first quarter of last year, the FDA, that's the regulatory body in the United States, their system is to appoint an expert advisory panel to review the evidence of efficacy.

13:53 And 10 out of 11 or 10 out of 12, I can't remember, had recommended not to approve the drug because the evidence wasn't there of any effect, any benefit. Nonetheless, the regulatory authority approved it and no one could understand why. Why would you have an expert panel who understand these studies to give you advice only to ignore that advice? And that that's bewildering. And in Australia we've got the Therapeutic Goods Administration and we'll have to see what their advice is by way of approving lecanemab, it's very likely that it might be approved. But from my perspective, I don't think we've got any pharmacological intervention that significantly alters the course of the disease. I think it's more hype to provide hope than real effectiveness.

14:48 Our strategy is very different. We're looking at preventing the accumulation of the drug and most importantly, preserving those brain capillaries because at the end of the day, brain cells have to utilise energy and nutrients coming from the blood supply, and that's only delivered by way of those microscopic blood vessels. If you lose their integrity, then you're doomed, essentially. So ours is quite different. It's a very vascular focused, it still has an amyloid consideration in that we think it's the amyloid in the blood that's disrupting the capillary integrity. And we think the deposition of that amyloid in the brain, which you see very late in the disease process, is really end stage. It's consequence, it's not cause. So I think they're targeting too late downstream with the current drugs that they're using.

Sarah Taillier: 15:44 What could be the impact, if that is approved by the TGA on the studies that are underway at the moment?

John Mamo: 15:52 For the existing drugs or for yours?

Sarah Taillier: 15:54 For yours, for clinical-

John Mamo: 15:55 Well look for ours, I'm led be really hopeful. We don't have any results yet. Our study is a double blind and it'll be some years away before we have that data. But in the best case scenario, at the moment, dementia is the biggest cause of death for women in Australia. Second biggest cause of death for the population overall, global population, which is getting older as Virginie indicated, and in my opinion and that of many others, we have no effective therapies on the horizon. This is one of the most costly diseases to manage and it will... There's forecasts, there've been massive reports on it. It will notionally, cripple health systems worldwide unless we go to a system where we just ignore it, lock people up and leave them to perish. It is frightening if you look into the details of what's ahead.

16:45 So we need really to identify strategies around prevention and strategies for treatment. And if you can just slow the disease by even five to 10% because of this occurs normally much later in life, then there's other biological factors which will come in, cardiovascular disease or cancer or something else, which will mean we'll see less incidents of Alzheimer's and dementia. I just might say that when you survey older age people globally, at least in Western countries where the data's available, their biggest concern by an order of magnitude is around dementia. People fear all sorts of death. It's a scary thing for many of us. But people are most concerned, older age people, older age Australians are most concerned about losing their ability to reason and to communicate and independence and recognition of their loved ones and families. It's their biggest fear, and that's by an order of magnitude compared to other major causes of death and disability in this country.

Sarah Taillier: 17:58 Given that fear and given the rates of death that go alongside this disease, are you surprised there isn't more urgency in this space? Obviously that is within your team, but outside of that?

John Mamo: 18:11 Look, I think there's a huge global effort to sort of look for strategies to treat disease. I think the way research is funded internationally, if you are pushing for a paradigm shift, it's incredibly hard to get funding. And we've experienced that for us to eventually secure funding to support our preclinical, that's before we went to clinical studies and the clinical trial was exhausting because the reviewers who look at your grants and your applications are so wedded to a school of thought, which is entrenched. So that's always really, really difficult. I'd like to think that us suggesting that Alzheimer's is really a disease of vascular origin, we're kind of reopening an old hypothesis in some ways, I think that would hopefully encourage a lot more interest and this possibility that the disease can occur outside of the brain because of things that are occurring around the way we metabolise fats, provides tremendous opportunity.

19:26 The one great opportunity we have with probucol is that there's no intellectual property that can be protected. There's too much. We've published our results in our preclinical and in some ways that was intentional. So you can't protect that commercially. So drug companies can't capitalise on that and probucol is very cheap to manufacture. It's incredibly stable. So in the best case scenario, and it would be a legacy and departure for me when I leave research eventually, but the legacy wish for me would be that probucol had some efficacy. We can support people so they can get another two or three years of good quality life, slow that disease down by providing them a drug which is going to be globally available. So there's many pharmaceutical companies that will make generic drugs and because they're selling so much of it, they're still going to make a very handsome profit. So at the end conclusion of this study, if it works, it can go global very quickly.

Sarah Taillier: 20:33 Well, I think there's a lot of people listening that are crossing their fingers right now for the whole team and for the study. Before we move on to the next part, Virginie, I just wanted to ask, you touched on it briefly a moment ago, what are the ages that are most at risk for Alzheimer's and some of the lifestyle changes you might be able to make in the lead up to that to reduce your chance of having the disease?

Virginie Lam: 20:55 Sure. So there's different age groups that are affected by Alzheimer's disease, but it's mostly the individuals over 65 years of age and above that are mostly affected by the late stage of the disease. So talking about lifestyle factors, thinking about different saturated fats, trans fats that can actually increase the amyloid beta burden that we've been talking about that probucol can actually target. So thinking about just lifestyle choices as well, being active, cognitive training as well is just, I like to think of Alzheimer's like heart disease in the brain really, is really keeping the brain active, keeping it healthy, keeping the vasculature. So all the brain capillaries we've been talking about, keeping them nice and functioning optimally.

John Mamo: 21:47 Do you mind if I add a couple of points just to that if you don't mind? There's two things that I think often get overlooked, which I think are really important. But a global phenomenon is our drinking culture. And Australia's got a huge drinking culture. And we know alcohol affects the integrity of the brain capillaries. It probably makes them more leaky. And our view as physiologists in our team is that it's the cumulative effect of multiple insults that put you at risk of developing any neurological disorder, not just Alzheimer's disease. So when you think of what you are doing over decades of life from a teenager, when you're getting loose, from our point of view, every poor meal you have, every alcohol drink that you have, you're adding a level of insult there. So it's hard to persuade people to think of long-term events and effects that have occurred decades in life later, but it is a slippery slope we're all on.

22:59 And occasionally it's good to reflect on when you're going through periods of life celebrating things, can you reduce those insults and reduce that cumulative effect? The other one I just wanted to mention is that we do talk about brain training and use it or lose it. The other critically important thing is around getting good quality sleep and resting the brain. So often people come home exhausted from work, what do they do? They might have a glass of wine, everyone's being fed, sitting in front of the TV, you're absolutely exhausted, but you've got visual processing, auditory processing, and it just continues to go on. And your brain is the most energy demanding organ that you can possibly imagine. It's got more spark plugs to utilise glucose than anything else. And I think we really underestimate the importance of just resting the brain. It's not always about brain training.

23:59 You wouldn't run a marathon and then go back and just continue to do some walking exercise or something. So it's great. Many of us are mentally challenged with the kind of work that we do. We get home, we've got stimulation constantly around us. We've got digital inputs constantly around us. And personally, I think it's critically important to find times to just cut it off, cut the inputs that you don't need off, and it can be little things. You could be driving in the car, do you have to have the radio on every single time? Is it all the time? Yeah, of course, we always want to listen to which podcast? Sure.

Sarah Taillier: 24:36 The Future Of.

John Mamo: 24:37 Absolutely. Exactly. But I think just resting the brain is something that we just really underestimate quite a bit. And considering is our sleep effective? What can we do to support better sleep habits? Really important.

Sarah Taillier: 24:48 That really backed the basics investment in yourself. I think you've both been able to really bring it home. We're just going to pause for a quick break. We'll be back right after this message.

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Sarah Taillier: 25:36 And we're back. Virginie, if Alzheimer's is a syndrome of brain degeneration and that degeneration can happen over a long period of time, how will we know to do something about Alzheimer's until it's maybe too late?

Virginie Lam: 25:51 Yeah, so just before the break, how John was talking about all the continual insults over decades of your life. So all these continued insults, we actually break down the bronch capillaries that are essential to cognitive function and memory performance. So it's really, really hard to be able to tell am I degenerating at the moment? And sometimes it varies individual to individual. You might get very minor behavioural changes, changes in reasoning, justification, cognitive impairment, but there are quite a few contemporary studies at the moment that are looking for different biomarkers to see these very early changes in the brain, whether it's through imaging, you've all heard of MRI scans, it could be through blood biomarkers. So we'll just simply take a blood test and see if there's changes in different proteins with brain degeneration. But there's still a lot of research to be done because there's research coming out every day where there's claim biomarkers, but there's still no definitive biomarker that can tell us exactly when this degenerative process is occurring.

Sarah Taillier: 27:00 John, another reason why Alzheimer's has been in the headlines of late was after Australian actor, Chris Hemsworth announced late last year that he was taking a break from acting after he found out he carried two genes that can increase the risk of Alzheimer's. Should we all be getting our DNA tested?

John Mamo: 27:18 Well, the short answer to that question is, no, I don't think we should, and in fact, I just remembered I wrote a little piece in the conversation recently about Chris Hemsworth and what that meant and how people should consider genetic testing. But if I can give your audience a little bit of insight. So the gene is called APOE, and you will inherit one gene from mum and dad when you're born. There's three versions of it, E2, E3, and E4. So you can have either two copies of one of them or a mixture of the two, if that makes sense. If you are an individual that's inherited one or two copies of the APOE4 gene, it gives you a much higher rate of, or higher chance of getting Alzheimer's. It doesn't mean you definitely got to get it, it's just an increased risk.

28:02 And there's lots of hypotheses as to why APOE4 promotes risk, but no one's really certain as to why. Our group took a different perspective on how APOE4 might be increasing risk for Alzheimer's disease, and we linked it to knowledge that's been around for a number of years. APOE4 is really very important for regulating the metabolism of fats in blood. So I'm taking you back out of the brain and into the bloodstream, and the APOE will basically direct where the lipids go, where they're metabolised. And in ongoing research that we have in the group, we are discovering... We haven't published this yet, so it's a bit insightful. We're discovering that the APOE4 appears to be associated with a defect in the clearance of that fat amyloid complex. Now, if that's sitting around in blood for a longer period of time, then you've got to get that capillary dysfunction and perhaps an acceleration of the disease process.

29:06 So we think that's the pathway by which APOE4 is increasing risk. But the question is, if you had that knowledge, what would you do about it? Well, you can't change your gene, right? But you can change your lifestyle and that's what Virginie was alluding to. So what we know so far is that certain components of diet can promote the amount of lipoprotein amyloid in blood. Too much of the Western style saturated fats is one of the drivers for that. We know that certain metabolic conditions such as diabetes can have a similar sort effect. So we want to maintain good metabolic health. We don't want to be diabetic, we want to control things like that. We know that exercise can promote the utilisation of fats and amyloid in blood. So that's another good thing to have. So I would say to your listeners that the best thing to do is to adopt the lifestyle changes, which we know are beneficial.

30:09 And if you're not sure what they are in terms of how they relate to health, just think of the heart. Everybody knows what you've got to do to protect the heart and basically if it's healthy for the heart, it's healthy for the brain. If you want to be more curious and you want to find out whether you've got an E4, well good luck to you. You can get a service provider to do that, but it just is going to tell you that you need to be even more careful. So an analogy is, I come from a cancer family. I can go and look at some genes that say, oh, I might be at high risk for cancer because of, but I know that those genes for cancer are all related to what I choose to do in my daily lifestyle choices. So I don't bother getting the gene testing. I just try and adopt and I try and be exemplary around my lifestyle choices. And that's what I encourage your listeners to do.

Sarah Taillier: 31:00 That's really empowering approach. I know that some people have made comparisons of it's better to know and to make those changes rather than to kind of stick your head in the sand. But obviously either way it makes sense to make changes now, regardless.

John Mamo: 31:16 Yes. I mean, you have to ask for any type of testing, whether if you had the result, would it change management of risk or management of treatment? And if the answer is no, then why do the test?

Sarah Taillier: 31:33 This question goes to either of you or both, what are your hopes for the future treatment of this disease?

Virginie Lam: 31:41 Well, ultimately we can... There's no cure to Alzheimer's right now, so it sounds a bit cliche, but being able to cure the disease because I've seen the devastating effects of dementia to individuals obviously who have the disease and family members and the effects in society as well.

John Mamo: 32:04 I'd like to see new preventative strategies that will slow or delay onset. I think it's probably inevitable as we live longer that people will succumb to this. But if we can slow progression, that's got to be enormously helpful to the person living with the disease, to their caregivers, to the economy and other biological factors will come into play. I think that's the best hope. By the time we see Alzheimer's or most dementias clinically, we've got to appreciate there's already been a lot of brain damage, which you are not going to reverse, but if you can stabilise that rate of deterioration, that's the target.

Sarah Taillier: 32:48 So is it ever too late to make some changes?

John Mamo: 32:51 No, it's never too late to make some changes. We all know what eating healthy is like. And the other thing I would throw in is that unless you've got a particular metabolic condition, your body will cue you in terms of what physiologically you need.

33:12 And I get really interested in that people really try and micro manipulate their diet, but you can have a balanced diet that doesn't have to equate to what you are eating over a daily basis. It could be what's occurring over a week or several weeks. Your body will cue you. And so often we ignore it. If you are craving something, your body is telling you you need something for a reason, that might be because you need energy or whatever it might be. And I think we need to be better cued in to what is the driver for what we are wanting to eat. Don't just succumb I'm going to eat chocolate because I just love chocolate and I crave for it. But sometimes chocolate's a really good source of energy and it's a really good neuro stimulant, and it could be good in certain context, students studying, for example.

34:07 So I think we need to be a little bit more in tune with what our body is actually suggesting we may need. The only time that fails is if you've got a certain type of metabolic condition. If you have diabetes and your body's not producing enough insulin or you're not utilising the insulin to utilise glucose effectively, you'll continually crave sugar because you've got a defect in that. But for the normal healthy Australian going about around their business, take the cue and you know what's going to cause damage and avoid it. I used another analogy, and you may want to edit this one out, but the one is if you have a wound on your hand somewhere, you wouldn't pick at it and then put a band aid on it and then pick at it and then put a band aid on it, would you?

35:00 And the vasculature and the microvasculature on the brain, I want you to think in that context, if you knew that alcohol or eating this particular meal is going to give those micro vessels a bit of insult, and then you eat well and you don't have alcohol. So they go into a recovery phase and then you do it again. You wouldn't keep picking at the wound on your hand. So why do you keep insulting what's occurring within your body, which you don't feel acutely at the time? And that's the way we have to think. Every choice you make, everything you put in your mouth, every lifestyle you choose to do has an impact on your physiology, on your functioning organs. And it's the cumulative effect of your lifestyle choices over years in life, which are going to dictate whether you're at high risk of dementia, cancer, heart disease, diabetes, and the list goes on. So if we can reinforce positive thinking about we're doing what we're doing on a daily basis, I think that's a great take home message.

Sarah Taillier: 36:07 Just finally to both of you, I'd love to know what actually inspired you to become researchers in this area?

Virginie Lam: 36:14 Well, I've always had a really, really good support team. I actually did my PhD with John, so you do learn from the best. And his passion is second to none, but don't only research Alzheimer's disease. We've recently been looking into preventative strategies, looking into our multiple sclerosis, and most recently chemo brain as well, which is cognitive impairment due to chemotherapy treatment for people with cancer. So there's a common theme there. It's mostly brain disorders that don't have a cure right now. So that's my big driver to hopefully make a difference no matter how small to the society.

John Mamo: 36:55 Yeah. Look, I go back to a concept around an old saying, which is the gift of giving. And you may have heard that they say that the giver actually gets more benefit than those who receive the gift. And nothing excites me more. And to be working with people of such knowledge, I find it such a privilege and to be blessed by people who are just wanting to improve the wellbeing of people's lives. That's what drives me. That's what pushes us through the cycles of not getting funding and working on some of these hare brain research concepts that we have. I think it's extraordinarily wonderful to be able to be pursuing lines of research inquiry, which just may, just may make things a little bit better for people who are facing really challenging health futures. I think that's pretty exciting, and I celebrate people who make discoveries like that every single day.

Sarah Taillier: 38:03 Thank you for both coming in and for sharing the wealth of knowledge that you have in this space and many other spaces and really striving to make those big changes in society. Best of luck with the study and the rest of your research.

John Mamo: 38:18 Thank you so very much.

Virginie Lam: 38:19 Thanks so much.

Sarah Taillier: 38:20 You've been listening to The Future Of, a podcast powered by Curtin University. As always, if you've enjoyed this episode, please share it and don't forget to subscribe to The Future Of on your favourite podcast app. Bye for now.