Brain Expert: Why Dementia Is Australia's Number One Killer (Project 100)

All content and media by Project 100 is created and published online for informational purposes only. It is not intended to be a substitute for professional medical advice and should not be relied on as health or personal advice. **** Professor Matthew Kiernan is CEO of Neura Australia and one of the nation's leading neurologists tackling the growing dementia crisis. Kiernan explores why dementia is now Australia's number one cause of death, the modifiable risk factors that could prevent 45% of cases, and the groundbreaking monoclonal antibody treatments now available for Alzheimer's disease. Kiernan explains how the Western Pacific region carries 60% of the world's dementia burden and why researchers are racing to develop blood biomarkers that could detect brain diseases decades before symptoms appear. We also get into: • Why dementia has overtaken heart disease as Australia's leading killer • The role of vascular health in brain function and cognitive decline • Blood biomarkers coming within five years for early detection • Monoclonal antibody treatments for Alzheimer's now available in Australia • The connection between contact sports, head injuries and neurodegeneration • How GLP-1 medications are showing promise for brain health • Sleep's critical role in clearing toxic proteins from the brain Join my exclusive Mentored+ community: https://mentored.com.au/become-a-member/ Subscribe to the Mentored newsletter here: https://mentored.com.au/newsletter See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

• 0:00Speaker 00

  Professor Matthew Kiernan, welcome to Project 100 again, mate. And we'll probably run this on Straight Talk as well, if you don't mind. Because I think there's a lot of people who are in the Straight Talk audience who would like to hear what Project 100 has got to say about this. So I appreciate your time.

• 0:13Speaker 01

  No, thanks very much, Mark. And I really appreciate what you're doing for the, for the community to raise awareness of brain health, mental health. It's a huge topic.

• 0:21Speaker 00

  And I was shocked when I became aware that the broad umbrella of dementia today is the number one cause of death in Australia. And so therefore it's over taking heart or coronary attacks or heart attacks. Or yeah, heart failure. First question to you is, is that just simply a result of us living longer? And therefore, if we got through cancer and heart problems, that eventually our brain's going to get us. Is that just that reason? Or are you seeing younger people getting it now?

• 0:58Speaker 01

  Well, I think it's a combination of both of those factors. But really, you know, as a, as a doctor, when I was a junior doctor, cardiovascular health was the key focus. And, you know, there was bypass surgery and people having heart attacks. And it was the number one. And so understandably, you know, politicians in the community put a focus on trying to understand the condition and treat it. And I think that's really the gold standard to understand that, you know, heart, heart health and heart disease. You have to look after vascular health, stop smoking, understand the risk factors, cholesterol, blood pressure, blood sugar levels. And it was with that understanding and then some therapies coming through.

• 1:41Speaker 01

  And I think, you know, everyone would accept that the statin evolution has changed cardiovascular health. And then a biomarker, so understanding that we can treat against cholesterol. And gradually you started to see cardiovascular deaths going down. In my fields in neurology, stroke was always going up every single year, higher and higher and higher. And then eventually. They did an epidemiological study and they saw that stroke was dropping. And the neurologists didn't actually believe it, like, how could this be the case? They repeated the study and sure enough, stroke was actually dropping. And it's because we've learnt from the vascular health approaches from, you know, cardiologists and heart physicians. And the same thing has happened.

• 2:23Speaker 01

  So while that's been happening, and then obviously all the great advances in cancer because of molecular biology, understanding genetics, the human, the whole human genome, all of these things that, you know, getting well understood. And no one has really focused on inverted commas dementia. And I suppose as a community, we've often thought that it's an elderly people's condition and we didn't really care about it. And, you know, okay, if we end up, you know, a bit demented in a nursing home, that's, that's the cost of living. But really what's happened alarmingly is it's really come to the fore. And we're seeing there's a huge amounts of dementia and neurodegeneration. And in fact, this geographical region, the Western Pacific, carries three fifths, so sixty percent of the world burden.

• 3:06Speaker 00

  What?

• 3:07Speaker 01

  Yeah. And it's going to be a massive cost with, you know, we're talking about the budget.

• 3:11Speaker 00

  What is that?

• 3:12Speaker 01

  Well, I think it's, it's an unusual sort of racial mix, but we've got, you know, obviously a lot of Asian populations. We've got South Pacific islanders. Obviously, we've got the Anglos from, from Western Europe. But it's a huge population firstly, and they're prone to vascular particularly related neuro problems. Dementia, vascular dementia in particular. And also I suppose there's a lot of underdeveloped regions. So if we think about our neighbouring countries, you know, we've, we've been very lucky and Australia's lucky and there's Japan and Korea. But then it's mixed with, you know, great poverty, Thailand, Myanmar, Burma, Thailand, um, you know, Indonesia, all, and huge populations.

• 3:57Speaker 01

  So the focus globally is to try and fix up the Western Pacific. And then take some of the learnings from the Western Pacific and do refinements, particularly in Western Europe and in North America. So as a neurologist, obviously I'm a bit prejudiced. I'm glad there's a focus on brain health because it's really going to be an evolution. And in fact, the, the reason I did get into neurology was, you know, George Bush Senior saying that the nineties were the decade of the brain. And the brain has been left behind a little bit. And now we're starting to understand these conditions. And we're going to be like the cardiologists of the nineties. We're going to understand risk factors. We're going to be titrating blood biomarkers. We've got effective therapies and it's going to be totally transformational.

• 4:40Speaker 01

  The joke about neurologists were they're really good at making a diagnosis, but they don't do any treatment. So you go to the neurologist to get your diagnosis and, you know, prepare your will. That was, that, that's the prejudice against us poor old neurologists. But dare I say it, we're going to a therapeutic era and, and it's really exciting.

• 5:00Speaker 00

  Okay. And, and part of that, of course, is in your role as CEO of Nura in the U R A. I'm at a, at a UNSW, well, across the road from the English, uh, uh,

• 5:13Speaker 01

  Yes.

• 5:13Speaker 00

  Horse stable, studying, whatever it is. But in, now Nura is a, as I understand it, as I recall, is a joint venture between UNSW and the Prince Wales Hospital, is that right?

• 5:24Speaker 01

  Yeah. So the South Eastern Sydney Local Health District and that includes Prince of Wales, St George and Sutherland. So.

• 5:30Speaker 00

  And, and, and it's a new initiative, but it's sort of pretty big. I mean, you've got a big premises, I've been at the premises, huge, all brand new. How many people have got in your?

• 5:40Speaker 01

  So about five hundred and fifty researchers focusing on brain health and mental health. It's amazing and I encourage everyone to come out and visit like you've done.

• 5:47Speaker 00

  Yep.

• 5:48Speaker 01

  And we're very keen to have, you know, really greater community involvement and, and connection.

• 5:53Speaker 00

  Is that the biggest undertaking in the country?

• 5:57Speaker 01

  Yeah, I, I would say it is. The other sort of big, um, centres around Australia would be the Florrie in Melbourne. Um, there's the Queensland Brain Institute, uh, in, um, Brisbane. And there's the Perrin Institute in Perth, but I think they're the biggest entities.

• 6:11Speaker 00

  Sounds like the biggest one in Sydney though.

• 6:13Speaker 01

  Yeah.

• 6:14Speaker 00

  Yeah. And, and, and does government support it?

• 6:19Speaker 01

  Well, of course the government does support it, but times are tough. And I suppose Nura was, um, established on grant funding. So National Health and Medical Research Council, so N H M R C and A R C, Australian Research Council, been very, very successful in grants.

• 6:35Speaker 00

  Did you have to apply for those grants?

• 6:37Speaker 01

  And, and. Present now, the success rate for grants is about eight to 10%. And the funding has really taken a battering and I was actually pleased in the budget to see an extra 508 million coming towards medical research and that had been driven by a campaign through medical research institutes, but also great advocates like Monique Ryan, who'd been pushing forward to try and get the MRFF amount fully released. But now with, you know, lowering government grants support, researchers have to reach out more to the community. And what are the best, what are the most successful ways? Well, the most successful way to fund your research program is have an industry partner. And industry, you know, they need to make money.

• 7:20Speaker 00

  For example?

• 7:21Speaker 01

  Well, any, any, any pharma company.

• 7:23Speaker 00

  Right.

• 7:24Speaker 01

  So examples that we're working with very closely include Roche Diagnostics, based in Switzerland, Eli Lilly or Lilly Pharma, United States. They're, they're, they're key, Teva, are key partners for us to drive our research programs. But the beauty about having an industry partner is you're more likely to have what we call impact and translations. In other words, your discoveries are going to make it out to the patient, to the clinic. And that's why the health districts and the university are engaged, because they want to see better health outcomes. So you're much more likely to get that if you have an industry partner. Now, the other key way that Nura has been surviving has been the support of the community. And we've been very lucky to have, you know, fantastic philanthropic support.

• 8:09Speaker 01

  And there've been individuals who've funded whole programs and, you know, developments of the building. Margaret Ainsworth is responsible for the, the main building at Nura. But I think we're starting to see that the community is investing in research with the desire to have better health outcomes. And it's really, it's, it's great to see.

• 8:29Speaker 00

  So let's just, you, you mentioned vascular dementia.

• 8:32Speaker 01

  Yeah.

• 8:32Speaker 00

  And maybe you could explain what is vascular dementia?

• 8:37Speaker 01

  So vascular relates to the blood vessels and dementia generally means problems with memory and cognition. And the brain is made up of nerves, neurons that have, has lining on it. And the lining of the myelin is supplied, the lining, which is called myelin, is built through cholesterol and apolipoproteins and all of those sort of bio, biochemical processes, but it needs a vascular supply.

• 9:05Speaker 00

  It needs a blood supply.

• 9:06Speaker 01

  It needs a blood supply.

• 9:07Speaker 00

  So you're, and maybe just, just for audience, those um, things that you just mentioned.

• 9:13Speaker 01

  Yeah.

• 9:13Speaker 00

  They're all fats.

• 9:14Speaker 01

  Yeah, they're all fats.

• 9:16Speaker 00

  Lipids, fats produced by our liver.

• 9:18Speaker 01

  Absolutely.

• 9:19Speaker 00

  We're producing that, we're.

• 9:20Speaker 01

  Endogenously, so inside our body, yes, we are producing it. And I think the other thing to say is the brain is a, is a network. So all of the brain is working, communicating with itself all the time. We used to think that, you know, one part of the brain might be memory, one part of the brain might be vision. But that was because we studied neurology on the basis of a deficit, like a stroke or an injury. In fact, okay, a lot of the neurology understanding came from major wars. So particularly World War One, bullet wounds in the back of the head, people would understand that's the cerebellum. And so it was looking at deficits. And one of the great neurologists is a guy called Charles Miller Fisher. And he said, you learn neurology stroke by stroke. So you see a patient with a stroke, you see what part of the brain is affected and then

• 10:05Speaker 01

  you see what the manifestation is that, and then that's your understanding. But now we see the brain more as a network. So all of these parts of the brain are communicating through these nerve fibers. And when the blood supply is affected, they start not working as well as they should. So the speed of the signal getting through is less, sometimes they die. So little parts and little holes start developing, small strokes, micro strokes in, in, at a very molecular level. So you wouldn't see it if you had the brain in front of you, but if you put it under a microscope, you'd see it.

• 10:39Speaker 00

  And you probably can't detect it either, um, while someone's alive.

• 10:43Speaker 01

  Unless there's a certain amount happening, like a volume, it's a volume effect. So we start to see it with MRI scans, but by that stage it's more often than not more severe.

• 10:53Speaker 00

  More a problem.

• 10:53Speaker 01

  So right at the beginning and that's the trouble, we don't know when this begins. So it could be beginning 20 or 30 years before the patient manifests any symptoms.

• 11:03Speaker 00

  And what causes uh this blood supply problem? Like in other words, I presume what we're talking about is a reduction in the blood supply.

• 11:12Speaker 01

  Reduction in blood supply. And it's really been driven, the understanding through vascular researchers, so cardiovascular health. So understanding that the the wall of the blood vessel gets thicker, the the sort of the lumen or the hole in the middle gets smaller, less blood gets out there. Sometimes the vessel actually breaks apart a little bit, a bit of ooze and you know, blood and proteins escape into the brain. That's that's the process. And if that happens, you know, in general areas. Interestingly, one of the sort of the key um problems that you see is people start falling over. And everyone thinks, oh, falls are normal. No, if you have a fall, that's abnormal. I mean, obviously if you have a fall, you're running and you chip on a gutter, that's understood.

• 11:56Speaker 00

  Yeah.

• 11:57Speaker 01

  But if you're walking around the house and you fall over, you're on the street and you fall over, that's abnormal.

• 12:01Speaker 00

  Your legs give away.

• 12:02Speaker 01

  Yeah, your legs give away or your balance is affected and you fall over. That's often the beginning of understanding that someone may be suffering from a vascular brain process. So falls are very much characteristically linked. The other thing is obviously your cognition. So so family members notice that maybe you're not as sharp as you were, you seem to be forgetting things. Um, you might be, I mean, sometimes, for instance, you might drive the car home and you know, hit the side of the car in the garage. You might not even mention you've done it, you know, another family member notices there's a dent in the car. How did that happen? So it's the the the behaviour and the fine tuning of motor function or brain function is being affected.

• 12:44Speaker 01

  And it's usually often the family members, people in the house, children, partners who notice and they try and encourage a medical review.

• 12:53Speaker 00

  Because I remember when I come and saw you just getting a checkup. Um, and you made me do some. Physical movements like walking and standing on one foot. Uh, and then you sent me off to get a, uh, an ultrasound or Doppler, I think you called it, on my carotid arteries.

• 13:12Speaker 01

  Yeah.

• 13:13Speaker 00

  So why would someone, when would a doctor tell someone to get that? And why would someone get that? What were those, and those, especially those tests where you wanna see my, um, they're old school physician tests. I remember I used to get, my doctor when I was a kid used to do that. But doctors since then stopped doing it. What are you looking for when you do those very fundamental tests?

• 13:34Speaker 01

  So it's about motor function. So we're seeing how someone walks, we're seeing their gait, we're seeing their gait length. And then part of that is what we call tandem walking. So the police stole our tests. This is a neurology test, but doing heel in front of the toe in a straight line. And these are markers for things like vascular dementia. Also getting someone to stand on the spot and close their eyes. Because if they're having problems with no function in their legs in particular, other, other senses start to take off. So they're relying on their eyes. But for instance, at nighttime, when they get up in the middle of the night, they fall over.

• 14:06Speaker 00

  Yeah.

• 14:06Speaker 01

  So that's a way to try, try and look at that. And coordination testing in a general sense. Reflexes are used for us to try to determine the level of, we, we use a word called lesion. Where is the lesions? We're trying to work out where the abnormality is. And by tradition, we see two, two, we divide the nervous system up into central, which is the brain and the spinal cord, we call it upper motor neuron. Or there's the peripheral, and that's the nerve and muscles in the arms and the legs. And reflexes tell us where to go. So in other words, if I test someone and they've got very brisk reflexes in a territory, so I just tapped them and, or I don't even need a tendon hammer, that's suggesting upper motor neuron or central problems.

• 14:49Speaker 01

  If I test their reflexes and I've got no reflexes in a region, that would suggest that the nerve supply is damaged. So that's, that's a peripheral abnormality. So we're trying to see, is this a central problem, like vascular dementia? Or is it a peripheral problem, like a diabetic neuropathy?

• 15:05Speaker 00

  Right. So, and then the, the carotid, um, Doppler?

• 15:10Speaker 01

  Yeah. So.

• 15:13Speaker 01

  It really depends on what the patient is presenting with. But let's say the presentation might be a partner's thinks that they're not thinking as well as they were, or there's a family history. And with family history, we use typically under the age of 50. So if someone has had, a family members had either a heart attack or a stroke under 50, that's significant. And so as part of my assessment, we do investigations. And the Doppler study is an ultrasound looking at the carotid and vertebral arteries. They're the main blood vessels that go to the brain, supplying.

• 15:42Speaker 00

  From the heart.

• 15:43Speaker 01

  From the heart directly. And if they start to get closed off slightly, that can be the, that can be the cause of the presentation.

• 15:53Speaker 00

  No, no, there was not enough blood flowing.

• 15:55Speaker 01

  Blood flowing out. And we use, again, about a 70% marker. So if it's less than 70% flow, that's significant.

• 16:03Speaker 00

  Right.

• 16:03Speaker 01

  But now with Doppler, with technology, we can actually trace that up. And we can go and now look at the blood vessels, the middle cerebral artery, posterior cerebral artery, which form a sort of circle inside the brain called the circle of Willis. So we can study that now through ultrasound. And again, we can get some marker about blood flow.

• 16:23Speaker 00

  Right. And so what would cause those arteries to do this? I mean, obviously smoking is an issue, but.

• 16:31Speaker 01

  Yeah.

• 16:32Speaker 00

  Is it just high cholesterol, high or low density cholesterol?

• 16:36Speaker 01

  All of those factors, but definitely smoking would have been probably the most common cause. And I've seen that evolution now, like in the 90s, we were seeing a lot of carotid artery. We use the word stenosis. It's less common now. People don't smoke as much as they used to. Like, it's rare that you see smokers now. You've mentioned then cholesterol, so understanding like LDL in particular, more than about 4.5 or more than two. But the total cholesterol of more than 4.5 is significant. Blood sugar levels and obviously, you know, your body mass index.

• 17:10Speaker 00

  What about the, the so-called APO B, APO lipoprotein B, I mean, which is the carrier? So of the cholesterol, most people don't realise. Cholesterol doesn't get anywhere unless it's got some, it needs a piggyback.

• 17:22Speaker 01

  Absolutely. And so.

• 17:23Speaker 00

  That's a new thing, is it? It's a new test.

• 17:25Speaker 01

  Yes, yeah, it's a, it's a, no, it's a new test.

• 17:28Speaker 00

  Yeah.

• 17:28Speaker 01

  And so apolipoprotein is one of, it turns out there's lots of different types, there's lots of different forms, you know, one, two, three, four, five. Four is the critical one, but these apolipoproteins help other processes, other nutrients come in and out of cells. But the issue about apolipoprotein E4 is that it is involved in the removal of amyloid and plaques. So if you have higher numbers or manifestations of that, the breakdown of amyloid in the brain is not as good.

• 18:05Speaker 01

  So that makes you more prone to Alzheimer's disease. So amyloid and tau proteins in the brain, they're linked to a specific form of dementia, Alzheimer's disease.

• 18:16Speaker 00

  Which forget, forget from, forget from us, basically can't remember stuff.

• 18:20Speaker 01

  Absolutely, yeah.

• 18:21Speaker 00

  And then that happens in one part of the brain, well, more prevalent than hippocampus or thing, is that, is that, is that right?

• 18:26Speaker 01

  That's the most common and that, that's the sort of the centre of memory function in our human brain. But it doesn't have to be there, like it could also be, some people start, you know, losing their vision. So it could be in the occipital region. Um, it can be lots of different parts of the brain, but the more common part, yes, is memory.

• 18:42Speaker 00

  And, and is it fair to say that, um, I don't know where I read this, but vision and, um, hearing are quite important as early markers for, but potentially you might be getting, your dementia might be coming your way down the track.

• 18:59Speaker 01

  Yeah.

• 18:59Speaker 00

  What, why is that?

• 19:00Speaker 01

  Well, I think this is really great work that came out from the Lancet Commission and they discovered 14 factors, uh, which could be modified to either prevent or treat dementia, modify or prevent. And one of those is hearing. And I think that it, you know, I have a colleague who's a neurologist and he started developing hearing problems and he noticed that when he went to dinner parties, he didn't really want to engage because he couldn't hear what was going on. So people start retreating. And that then promotes the brain not to function as well as it, you know, normally.

• 19:33Speaker 00

  Retreating from what, social interaction?

• 19:34Speaker 01

  Social engagement.

• 19:35Speaker 00

  Oh, really?

• 19:36Speaker 01

  And so, social engagement is another critical factor that was identified by the Lancet Commission. So the more that you're engaged in, you know, a profession, a work, a environment, a community, a sports environment, a rugby league club, the better off people go. And if you're isolated, the brain, the brain doesn't like isolation. So this is all, these are all modifiable risk factors. And then how could you sort of cut off a few of them? Well firstly, like if you like exercise, are you involved in a, in a community approach? Or is it a particular exercise that you like doing? Aerobic type of exercise, but also resistance training? And these again are modifiable risk factors for dementia.

• 20:19Speaker 01

  Another part of that, that's only really come out in the last few years is an understanding what we call frailty. So you might've said, oh, someone looks a bit frail, that doesn't really mean anything. But frailty is, it's a two-way process between the body and all of the body organs and the brain. So when the brain stops working, the organs don't work as well. But if the organs don't work as well, the brain stops working in converse.

• 20:42Speaker 00

  So you don't allow yourself to get frail?

• 20:44Speaker 01

  Yeah, so how can you prevent yourself from becoming frail? Well, resistance training, high protein diet, aerobic training, stay engaged with the community. These are the things that are going to help brain health.

• 20:55Speaker 00

  I remember Mark Penny, Professor Mark Penny, he once told me about, because I was talking about to him about his dad, Ron, who, who died from dementia. And Ron was like a genius, skinny, fit, walked up the stairs to a level, whatever it was, every day at St Vincent's. And, and I said to Mark, are you worried about your genetic predisposition perhaps? And would you bother getting a genetic test for dementia? And he said, no. And I said, why? And he said to me, the reason why, he said, is because even if I find out, the solution right now, I don't have any symptoms, but the solution right now would be to do high intensity exercise. And he said, so I might as well do it anyway. Whether I get a diagnosis or not, therefore I don't need the diagnosis because getting

• 21:40Speaker 00

  a diagnosis can cause a lot of anxiety and people do retract socially and all sorts of things. He said, I'm better off probably not knowing and but but doing the the very thing that they would recommend me do anyway. And and and so how does high intensity exercise assist in that regard?

• 22:00Speaker 01

  Well, I think obviously he was a visionary, but yeah, um, when you exercise, for instance, blood vessels dilate. So the blood vessels dilate, more blood flow starts going through.

• 22:09Speaker 00

  In your brain, you mean?

• 22:10Speaker 01

  In your brain and all over your body, but in your muscles. So that's just reflecting what's going on. But a number of conditions are also associated with other metabolic changes in in the brain and the body in a general sense. So insulin resistance, um, metabolic health, mitochondrial function. So all the cellular approaches, inflammation, inflammation in the brain, inflammation in the organs of the body. So all of these are improved through exercise and high intensity exercises, as Mark Penny suggested back then. I think the other thing is, and I and I understand what he's saying as well, there's a stigma and people don't necessarily want to be associated with any of these conditions like, but I I think what we've got to do is try and turn that around as a community and say, well, we're focusing on brain health.

• 22:55Speaker 01

  We want optimal brain function and we want to get into it early and we want to maintain it throughout the course of your life. So wouldn't it be great if people started going to their general practitioners at the age of thirty and had a brain health check to prevent dementia and neurodegeneration in their sixty, seventies, eighties, nineties? We don't know how long we're going to live for, but it's still going upwards. So I think that we can try and encourage a more healthy approach to brain health.

• 23:23Speaker 00

  It was funny, you know, today, knowing I was going to talk to you, I actually had an appointment, just a general point with my um, GP, who's actually fantastic. I've got to give him a, I've got to shout him out now.

• 23:35Speaker 01

  Great.

• 23:36Speaker 00

  And he's new, he's new, he's a young guy, new. And and he and I have all sorts of conversations similar to you and I about all sorts of things. And and I said to him, I wonder whether or not um,

• 23:48Speaker 00

  I should have, say, two days off from exercise and go and get a blood test for BDNF, brain derived nootropic factor. And he said, oh, he said, okay, that's not a bad idea. And but he couldn't find anywhere who does that. He's still searching. He hasn't texted me yet, but he's still searching. And the only reason I was saying that was because, you know, I'm, the thing is, you know, as you know, my mother passed away from motor neurone disease or ALS, and I've got dementia on the other side. So, you know, I get nervous about these things. But I but not so much that I'm over nervous, I'm not paranoid. But but I take the view I'm in control, I've got to do something about it. I've got to talk to people. That's what this whole show is about. And and I thought, well, I, as I

• 24:31Speaker 00

  understand it, that particular molecule that gets produced in your brain when you exercise is very good for brain health. But no one knows what the level is. No one's actually asked me to do a test. And I'm assuming he can find, he can find someone who can do it. You probably know the answer to that anyway. But what are some of the things that you think Australians or people listening to the show should be asking their doctor to get tested, even if it's just baselining you now in relation to brain health? Are there things that you should be asking, apart from the obvious ones? And the obvious ones are the heart, what's good? You once told me, if it's good for your heart, it's good for your brain.

• 25:11Speaker 01

  Exactly.

• 25:12Speaker 00

  Yeah. But apart from those, you know, APOB, little A, E, you know, that stuff, apart from those ones, are there any specific things you should be getting tested when you ask for a blood test from your doctor relative to your brain health?

• 25:25Speaker 01

  Well, you've already articulated the main ones currently. But this is a rapidly evolving landscape. So for instance, at Neuroscience Research Australia, we've formed a partnership with Roche Diagnostics platform. And part of the reason for that is to get blood biomarkers as a Medicare item number so that people can go to their GP and have all of these.

• 25:46Speaker 00

  Get done for free.

• 25:46Speaker 01

  Yeah. And that's where it's going to be. That's going to be in the next five to 10 years.

• 25:51Speaker 00

  Right.

• 25:51Speaker 01

  And some of those markers are specifically, you know, identified with particular conditions. But there are things called neurofilaments. So the neurofilament goes up in your blood when there's been some nerve damage. There are other markers we call GFAP. These are blood tests that can suggest a particular diagnosis.

• 26:17Speaker 01

  There's been a huge study in the UK and they've, you know, taken blood and um clinical examinations from fifty thousand people and they've gone back to the blood biomarkers and they're showing that if five, five particular proteins in the blood go up about ten years before Alzheimer's disease develops.

• 26:33Speaker 00

  Wow.

• 26:34Speaker 01

  And that, that's where we're going to be going. So we're going to be testing these in healthy individuals and then we can start to treat against these blood biomarkers to try and maximize brain health. It's not here at the present, but there's a lot of work going underway right now.

• 26:50Speaker 00

  Can you hurry up? Mate, I can't wait forever.

• 26:51Speaker 01

  Yeah.

• 26:52Speaker 00

  No, but because one of the things I wanted to ask you is, can you test, can I do a blood test today for um amyloid and tau?

• 27:02Speaker 01

  At the moment you can't, but that's exactly, so this sort of diagnostic pathway is to be doing amyloid and tau for, for Alzheimer's disease, TDP forty three for motor neuron disease and frontotemporal dementia, alpha synuclein for Lewy body dementia, Parkinson's disease. That's where it's going to be. And we're going to see what are those levels. But we can't really, at the moment, we haven't done large population studies to know what that range should be. And also, as you say, we don't panic people. No.

• 27:29Speaker 00

  You don't have a range.

• 27:30Speaker 01

  That's, that's cutting edge research now. Yeah.

• 27:33Speaker 00

  So do you think in the next five years, these are, some of these are, you know, realistically able to be done?

• 27:39Speaker 01

  I'd say with absolute guarantee, they will be. And you'll be going to the doctor with a blood result, like you do now with a full blood count, hemoglobin, and they'll say, oh, your neurofilament is slightly high. This is the treatment to bring it down, you know, towards roughly normal levels. Or that's really high, we need to do some more investigations on that one. We need to do a lumbar puncture and MRI scan. So I think it's going to start to determine the, the way forward. But then also linked to that, we're going to start having treatments. And we have now two, two treatments for Alzheimer's disease, monoclonal antibodies. And there's a lot more on the horizon coming through. So it's a very much a therapeutic era.

• 28:15Speaker 00

  Wow. So I do want to talk about those monoclonal antibody treatments in a, in a moment. Um, because I have one, as you know, I text you, but I have one, one friend of mine who's in his eighties and uh, I don't know whether it's him or his wife showed him this thing and he, you know, as I have this show and he sent me the text and I said, don't worry, I'm gonna get Matthew Kinnon, I'm gonna ask him the question. Because he, he actually is worried at, at his age about dementia, you know, genuinely worried.

• 28:43Speaker 00

  By the way, he's in great shape, but um I but people do get nervous about stuff, mate. They get really anxious. I mean, I think there's more anxiety. Of all the guys I know around my age, the one thing that particularly the ones who played footy or boxed or did anything like that had were in contact sports, they are all worried about dementia. It's like, it's a big deal. You'd be seeing as a neurologist, but it's a big deal.

• 29:09Speaker 01

  Yeah. And I think, again, industry has taken that on board as well. There was recently a superannuation conference and all of the key super providers, you know, imagine you've done your whole life, you've worked, you've you've set yourself up and then your cognition goes down. So it's it's incredibly important and I can see why people are worried. I'm worried. But we don't have a way to identify who is who is at the greatest risk at the moment. But the and that's why the focus on making brain health, you know, the key treatment area for our community is is critical and that and that's why it's happening. Everyone's worried about it.

• 29:45Speaker 00

  Yeah, well, governments should be worried about too, because, I mean, their job is, in my view, their job is to increase our standard of living, our standard of living, that the ultimate is about standard living and and there are lots of measurements for that. One measurement that should be how long you can live on this planet and how we live during that period. Um, and living with dementia, like when it's full blown at least, um, is not living, you know, like it's pretty dreadful on everyone else around you. Like if you someone said to me today or to you or anybody, look, you know, how would you see yourself when you're eighty five or ninety? And by the way, medical technology will get us here now because they can fix the heart, they can replace the heart, they can fix the kidneys, they can fix just better, everything except this

• 30:25Speaker 00

  thing. Um, and if if they said, if you were to rate your standard of living, one thing is you probably don't want to be confronted with is your kids happen to behave you and not be recognised by you, or your kids happen to put you in a nursing home because you you turn a little bit violent because you've got dementia. Um, that would be probably the the lowest standard of living I can I can imagine for me. And I'd say a lot of people would agree with that.

• 30:53Speaker 01

  Yeah.

• 30:53Speaker 00

  That's the fear.

• 30:54Speaker 01

  Absolutely.

• 30:55Speaker 00

  It's a massive fear.

• 30:56Speaker 01

  Yeah, and it's well founded. I think that the the the essence of being a human is our brain function, our executive function, the fact that we're having this conversation now. So when that is affected in any way, it has massive implications. And it's very hard for individuals and families to cope with that.

• 31:16Speaker 00

  So what if I could, I just had a thought then, if Matthew, if I could just go back to something. When you, when we're talking about high intensity exercise, you can do that when you're forty, fifty, sixty, some people maybe seventy. But it largely depends on your mobility and a lot of other stuff, you know, energy levels, et cetera. But when you're eighty, does high intensity then mean? I mean, how do we measure high intensity? Is it about my heart, my, my, as a percentage of maximum heart rate? Or is it, and therefore, you know, take a hundred and two twenty to minus eighty? And that gives me one forty, I mean, and I go try to get eighty five percent of that? Or or is it, you know, what is it? What is high intensity exercise?

• 31:58Speaker 01

  Well, that is exactly it. But I suppose when you're eighty or ninety, are you going to suddenly do a high intensity exercise for the first time and do it as well as a twenty year old? No, so you're going to be doing it in your twenties, thirties, forties, fifties, sixties, seventies and eighties. And in fact, by doing that, it makes it more likely that you are going to be able to do it in your eighties, nineties and one hundred. I see a lot of people who come in who were in fantastic health in their eighties and nineties. So that's the message. You don't have to be in bad health. You don't have to have, you know, disability. So but that that hasn't come out of nowhere.

• 32:31Speaker 00

  Yeah.

• 32:32Speaker 01

  So it's it's like doing homework all day, every day for the course of your life.

• 32:37Speaker 00

  Yes, and to that extent, and that's what this shows a lot about this is that they've got to take control. Individuals, we might, but they're not going to take control unless someone makes them aware. And and sort of gives them a bit of an indication of the type of life, that's lifestyle stuff.

• 32:53Speaker 01

  Yeah.

• 32:54Speaker 00

  Change your life, no, don't drink as much. Don't drink at all if you can help it. No cigarettes at all. Eat the right foods, don't put on too much weight, exercise properly. Sleep is really important. I do want to talk to you about something, this this apo E.

• 33:16Speaker 00

  Chris Hemsworth did his show on whatever the streaming platform was. He talked to Peter Attia. Peter Attia did a blood test on, you know, one of the most athletic looking people in I've ever seen on television. And I dare say he therefore is athletic. He's young and the bad news as delivered by Peter Attia to Hemsworth was that he had two alleles of E4, one from dad, I presume. Must have been my father and he was E4.

• 33:49Speaker 00

  One, could you comment on is, are we now testing for this stuff more, more, more often? And two, what does it mean?

• 34:02Speaker 01

  Both excellent questions. We are testing for it more often, but it's not routine and people often need to ask for it. So I think it's important, and that's why this show is important to understand that this is part of a risk factor for, you know, conditions such as dementia. And if you have alleles of ApoE4, as you mentioned, that means that you're less likely to break down the proteins that cause dementia in the brain.

• 34:28Speaker 00

  Because if that protein, E4, or if it's E2 or E3 operates more efficiently than E4.

• 34:37Speaker 01

  Absolutely.

• 34:37Speaker 00

  Is that the issue?

• 34:38Speaker 01

  Yeah.

• 34:39Speaker 00

  And if you've got E4, you don't have E2 or 3, or 2 in particular, you're not as likely to break down the, so it's not that efficient in getting rid of all the debris that's hanging around in your brain.

• 34:50Speaker 01

  Yeah, and it's still working, but it's not working as well. I suppose the comparison of, you know, 1970s, you know, Mini with a Tesla or something like that, like it's totally different. But it is, it is working to an extent. So obviously if you do have ApoE4, like Hemsworth showed on, on his show, that would put you at a higher risk. So that would put more emphasis on you to focus on all the other modifiable risk factors that you can control, the ones that we've already talked about.

• 35:23Speaker 00

  A statistical higher risk.

• 35:24Speaker 01

  Yeah.

• 35:25Speaker 00

  It doesn't matter. It's not a death sentence.

• 35:26Speaker 01

  No, and these are based on, and that's a good point. These are based on populations. This is population health. However, you can extrapolate the population to the best for you. But of course, an N equals one, i.e. yourself, it's like, it's not, it's not an exact science.

• 35:43Speaker 00

  Yeah. So, and I, as I understand it, there is something like people who pass away with perhaps Alzheimer's disease or some form of dementia, probably heart attacks too, but

• 35:57Speaker 00

  have a ten, ten times more of those people have the genotype E four. With both, they're going by both parents. It's a ten time factor. So in other words, it's correlation. It's not a causation. But let's say, and look, he looks great. I mean, and obviously he's adjusted his lifestyle. And by the way, I don't mind telling everyone, I'm E three, E four. So I got E four from one of my parents. Um, don't know which one, but one of them. Um, and I don't know who to blame. It's one, mum or dad. It doesn't really matter because they both passed away. But, um. Point being is that there's a, I don't know, six time, I don't know, ten times chance of like some other statistical greater chance of

• 36:41Speaker 00

  having a brain disorder or even a heart disorder, because E four actually affects your heart too. Like it's a bad for your heart. As you always say, if it's not good for your heart, it's not good for your brain. Um, E four does that too. And also has effect on your kidneys. It's a kidney issue too, by the way, because it's the same deal.

• 36:54Speaker 01

  Absolutely the same deal.

• 36:55Speaker 00

  Yeah, because your kidneys can get, uh, the, the, the, the arteries can get, uh, the ones coming out of the kidney can get damaged.

• 37:04Speaker 01

  Yes.

• 37:04Speaker 00

  Because, yeah, hardened and then they don't filter as well. And next thing you know, you start getting early kidney disease.

• 37:11Speaker 01

  That's exactly.

• 37:11Speaker 00

  So it's, it's a big deal.

• 37:12Speaker 01

  Yeah.

• 37:13Speaker 00

  And we should be getting tested for this sort of stuff more often. Um, so E four, just to explain a little bit more, if you don't mind. Because one of the things that, as I understand it, um, Matthew was that. Tau comes after amyloid accumulation and tau come about as a result of other processes that happen before that, way before those things start getting produced. And, uh, and there is, um, you know, they're talking about, you know, the CRISPR process projects whereby they can turn some genes off that some people have in their brain, whether they've got E4 or not,

• 37:58Speaker 00

  that you can turn off these processes where certain molecules are not going to get produced, which ultimately end up in producing more amyloids and tau. Can you just talk about the advances in CRISPR and what CRISPR is?

• 38:11Speaker 01

  Well firstly, I'd say that focusing on a particular gene that might do one part of a function, that's, that's, it's great research, but it, it might not necessarily have any impact or translation into the humans that we are. So I think that's the first thing. You often see these great discoveries and oh, we've been able to modify.

• 38:30Speaker 00

  Did it on mice?

• 38:31Speaker 01

  Yeah, did it on mice. And, you know, in a lot of the conditions we're talking about, all of my studies have been negative because how good is that model for the human disease?

• 38:40Speaker 00

  Right.

• 38:41Speaker 01

  And the other thing is, we've obviously mentioned amyloid and tau and they're important parts, but they're not the whole story either. And so there's a discussion, I remember when people were talking about amyloid, they said, well, it's like saying if you remove smoke, is that the end of the fire? No way. So there's a whole process going on here and amyloid and tau are critical parts and the genes modifying them are critical parts. But if we remove all of the amyloid out of someone's brain, will they be back to normal? Well, no, they're not because we're doing that now. So we can remove the amyloid with the monoclonal antibodies. And they don't go back to normal. They might either plateau or they might, you know, might slow down the progression. But then the question is, can we fine tune that? When do we start it?

• 39:26Speaker 01

  Do we start these medications at the age of thirty? When we see a BoE four is up and monitoring some other parts of the biomux? And that's where we're going. We're going to go earlier and earlier and earlier. And it might be that one of the medications is related to a gene modification in amyloid in a few years' time, but that that's not available at the moment. The other thing is when you start knocking out certain genes, you don't know what the downstream effects of that are.

• 39:51Speaker 00

  The knock on effect is.

• 39:52Speaker 01

  Yeah, exactly.

• 39:54Speaker 00

  Cause it might be good for something else.

• 39:55Speaker 01

  Yeah, and it might be a catastrophe. You know, there were, there were trials, for instance, in Parkinson's disease, putting in stem cells into the brain and all sounded great, it was looking good. But then the stem cells started to, you know, overgrow and cause, cause cancer. And so people were coming in with, you know, overgrowth and cancerous cells in the brain. So it was a catastrophe. So you've got to be able to understand, and that's really why human trials are so critical. So a model is only as good as the disease it models. But I think we have to get more and more into patients and patients with neurological conditions. Of course, we need basic science and discovery, but we've got to focus on, on the human.

• 40:35Speaker 00

  It, it, um, we, we are talking, I mean, dementia covers a lot of stuff and we've been talking about, and Alzheimer's the one probably everybody tends to focus on, but lost some memory, I guess, is probably my, my of describing it. Um, what is the general progression though? From the moment you, and I remember asking you this question. Um, I said to you, sometimes I just can forget a word and I just can't remember the word and, uh, in about two or three minutes it comes to me or I forget a person's name. I know them so well. But I haven't seen him for a while. And you said to me something like, um, that's sort of anxiety memory. Um, how did, because so many people say to me, oh, my God, can't remember that word.

• 41:19Speaker 00

  And there are older people and they're going, and they're just mucking around, go, uh, bloody early dementia. But what, what, what, what other things could be causing us not to remember the, the, the, the name or the, the word? What is this anxiety about memory?

• 41:34Speaker 01

  Well, I think once we start focusing on it, we all become anxious. Like hearing your story there, I was feeling a bit anxious. Um, so that's something natural, but I suppose you're worried that you can't recall a name or, or a process. And then a little bit later you do. So the function is there. So you haven't lost the function.

• 41:51Speaker 00

  Right. Alzheimer's means you lost the function.

• 41:53Speaker 01

  It doesn't, doesn't come back.

• 41:54Speaker 00

  Right.

• 41:54Speaker 01

  Or, and it's like, I suppose an onion, you start stripping away. The very core parts often remain and you might, you know, have memories from longstanding memories about, you know, growing up and your parents and so on, but you don't remember, um, that you need to go down and get, you know, to Coles and get dinner for tonight, those sort of things. So it's, so there's a level of, of what is intrinsic in your brain function that's laid down. And these, these are memories that are laid down and reinforced. But it's the short term issues that tend to be more problematic. And that also means your daily function in, in your job, in your family, in your environment.

• 42:31Speaker 00

  So what is the usual progression? So people start having, maybe what, what's something that someone might come to you and I'd obviously, I don't want to breach any professional situation, but like, maybe someone comes to you and like very early stage, Alzheimer's, like what would you, what would you see?

• 42:52Speaker 01

  Well, part of it can be prolonged word finding difficulties and, and we might test for it. Like you, you might show them a picture of, say, the Eiffel Tower and everyone says, oh, it's the Eiffel Tower. So what's that? Um, that's that place that's sort of, um, not here, but it's, and it's, and it's made of metal. And they're sort of talking around. So it's fluent, it's fluent speech, but they can't say Eiffel Tower. Or they can't say that's a structure in Paris and Paris is in France. So the connections. Are all gone.

• 43:19Speaker 00

  There are tests for this, specific tests, like, yeah, you, you have them.

• 43:23Speaker 01

  And so either the neurologist will be involved in those tests or there's a neuropsychologist. It's usually a multidisciplinary approach. And there, there's testing for word finding difficulties, but also then trails. So for instance, doing networks of, you know, shapes and sizes, doing images of clocks, understanding times. Um, another, you know, test is verbal fluency. That's the, the frontal lobe function. So for instance, um, I don't know if you want to do it on the spot, but tell me all the letters, all the words that you can think of with the letter M.

• 43:56Speaker 00

  Yeah, um, words.

• 43:58Speaker 01

  Yeah.

• 43:58Speaker 00

  Um, material, uh, master clock, um, I can't even think, um, they got me nervous.

• 44:07Speaker 00

  Can I think of names?

• 44:08Speaker 01

  No, no.

• 44:09Speaker 00

  I can't think of.

• 44:09Speaker 01

  Objects.

• 44:10Speaker 00

  Uh.

• 44:11Speaker 01

  In the dictionary.

• 44:12Speaker 00

  Money, metal, uh, motor car, motorcade, um, uh, uh, mammoth. Um, milestone, mightiness, uh, Michelangelo, um.

• 44:30Speaker 00

  How's my time going?

• 44:32Speaker 01

  Perfect. You still got about another 10 or 20 seconds, but more than, more than double figures in a minute is normal.

• 44:38Speaker 00

  Normal.

• 44:38Speaker 01

  Yeah.

• 44:39Speaker 00

  Yeah.

• 44:39Speaker 01

  And also you're looking at the words you used there, like, like some of those were three or four syllables. So they're very complex words. It's totally normal.

• 44:46Speaker 00

  Yeah.

• 44:46Speaker 01

  But these, this is part of the.

• 44:48Speaker 00

  So, but what, so how would someone know that Matt, um, that they should go and see someone? So, cause you know, like, let's say I could get two, two out, like for example, then I was, I'm sort of a bit late to the game. So to talk to a neurologist, um.

• 45:03Speaker 00

  Is there some sort of not self-testing? Is there some, like, can they go to the neuro website and your web, your, your website sort of explains a few things to me? And maybe gets me started to think about it, or I might be talking to my brother who's younger than me, but I might have noticed something I can say, mate, you just should go and see a doctor about this. I mean, how, how far back can we go?

• 45:21Speaker 01

  Well, we have got risk assessment profiles through the neuro website and people can, they're, they're all free.

• 45:26Speaker 00

  Is that neuro.com.au?

• 45:27Speaker 01

  Yeah.

• 45:28Speaker 00

  Dot U, yep.

• 45:29Speaker 01

  And, um, I think it's also just your engagement in, in life, like people like Sudoku's or reading the newspapers or, you know, looking at the stock market, talking about the, uh. The budget, all of those sort of things are sort of, they're markers that things are going okay. The tests that we're talking about are more biomarkers following a clinical presentation. So someone has been brought in either on their own volition or by a family member or a friend. Like, you know, Matthew's not, Matthew's not the same person that he seemed to be. Or there seems to be some minor, like high level stuff. And then we would go into this sort of cognitive assessment. And then that cognitive assessment would suggest what we need to do.

• 46:09Speaker 01

  Like it might say that actually, cause part of it as well is assessment of anxiety and mood. So I might score badly, but I might be like really, really down um in my, in my mood score. And then if I can improve my mood score, does the cognitive process come out? That's, people use these word pseudo dementia. So in other words, it's not really dementia, it's something else that's triggering the process. We'd also then, you know, look at, you know, blood test results, vitamin levels, thyroid function. These are all markers that will help brain function and they could account for the presentation.

• 46:44Speaker 00

  Wow. And so like this whole, I hate this word, but ecosystem around the outcome is pretty important. It's not just one thing. It's not just going to sit in front of a neurologist and he goes, oh, you've got it. Or you're at early stage. And what's the progress? So, I mean, where would someone end up? Let's say someone starts at seventy, they've got early dementia and, you know, diagnosed.

• 47:11Speaker 00

  Is it ten years or fifteen years a minute? And then, and what, how are they at the end of it?

• 47:16Speaker 01

  Well, the beauty is, back to the autonomy issue, people can have some control of the modifiable risk factors. So let's say I was not scoring as well as I should be, or I'd been measuring it over the last ten years and I was starting to drop off. If I start to adjust some of my lifestyle factors and some of the blood results I've got, can I either plateau out or start to raise it again? And, and these are things that, yes, we can do. So when you say, is it ten years, is it fifteen years? Well, no, it's all modifiable. So forty five percent is modifiable. So you've got control.

• 47:49Speaker 00

  Right. So as long as you know that.

• 47:51Speaker 01

  Yeah, as long as you know. So as long as you've been tested.

• 47:53Speaker 00

  And as long as.

• 47:54Speaker 01

  And part of that as well, blood pressure. So how often do you get your blood pressure checked by your general practitioner? If you're not seeing a general practitioner, go and see your general practitioner, get your blood pressure checked.

• 48:01Speaker 00

  Go and buy one of those Omron things, whatever they're called, from the chemist. I've got one at home.

• 48:04Speaker 01

  Yeah.

• 48:04Speaker 00

  Just every day.

• 48:05Speaker 01

  Yeah.

• 48:06Speaker 00

  The only problem is it would be great if I could somehow talk to my phone. There could be some sort of app to it that I could actually, you probably can't get it, mine's old, but actually I can have a record of it, I can actually see the changes, but.

• 48:17Speaker 01

  Well, more and more that's happening.

• 48:18Speaker 00

  It's a hundred bucks. It costs a hundred bucks.

• 48:21Speaker 01

  Exactly.

• 48:21Speaker 00

  And the whole family could use it and you can use it forever. And so, but in the end, what does a person from dementia die from?

• 48:31Speaker 01

  Very good question.

• 48:33Speaker 00

  It doesn't kill them, does it?

• 48:35Speaker 01

  Well, it does, but it's back to the brain is the, the, the sort of executive function controlling all other organs. So usually part of that is you're breathing, so you don't necessarily, you know, breathe as, as, as quickly and as deeply as normal. So that, you know, the base of the lungs don't fill up with air as they normally do. Some fluid might stay down there, you might aspirate, so you might swallow your food incorrectly. There'll be a chest infection, you'll die from pneumonia.

• 49:02Speaker 00

  So you die from pneumonia?

• 49:03Speaker 01

  That's the most common, but alternatively, it also does control, you know, your heart, your heart rhythm. People have heart attack, like they, they, they just die in their sleep. So the brain is controlling all of these functions, but yeah, that, that's how you die.

• 49:16Speaker 00

  As you know, um, my mother was, went to the other place she used to be at. Brain and mind centre when she had motor neuron disease and she died of motor neuron disease. Um, and it's a, it's a, it's a crappy way to die, to be honest with you, it's one of the worst. I've, I've seen lots of people pass away and that's probably the worst thing I've ever seen.

• 49:36Speaker 00

  Motor neuron disease is different to dementia.

• 49:41Speaker 00

  And say someone like me who's, you know, had lots of concussions, mini concussions and major concussions.

• 49:50Speaker 00

  Is there any scientific evidence?

• 49:55Speaker 00

  Or even statistical evidence about, that correlates concussions to ALS or motor neuron disease?

• 50:03Speaker 01

  Yeah, well, just to put it into a bit of perspective, so motor neuron disease is a neurodegenerative condition and neurodegeneration incorporates dementia. Dementia is due to, say, Alzheimer's disease or vascular dementia that we've talked about. Motor neuron disease is due to a protein abnormality in the brain as well called TDP forty three. It tends to affect particularly the motor pathways. So the corticospinal tract, which is a tract that goes through the brain and spinal cord and controls all of our voluntary muscles. So the motor neuron itself is one of the biggest cells in the body. Sometimes it's up to one point four metres long and it has huge

• 50:42Speaker 00

  metabolic. What, one point what?

• 50:43Speaker 01

  One point four metres. It's huge.

• 50:46Speaker 00

  That's massive.

• 50:46Speaker 01

  Massive, but it has high metabolic needs.

• 50:49Speaker 00

  Which means what?

• 50:51Speaker 01

  It requires a lot of, you know, protein. It's very sensitive to not having things, you know, waste cleared out properly. So it needs, you know, all the things we've talked about, healthy sleeping habits, good protein, good nutrition and exercise. But for what, for some individuals in the community, they're prone to having a disease whereby the degeneration occurs in the motor neuron itself. And so people start to develop weakness. It's usually focal. So in our clinics, we give a picture of a human and we say, where did the disease begin? And they can always pinpoint whether it began in my right hand, whether it began in my mouth, whether it began in my left leg.

• 51:33Speaker 00

  You mean the patients can?

• 51:34Speaker 01

  The patient. So it always begins, it seems to begin in one area and then it starts to spread and become a bit more generalised.

• 51:41Speaker 00

  So just explain where that cell is, that one point four metre.

• 51:46Speaker 01

  So it starts, it starts in the brain and goes all the way down through the spinal cord. And then there's what we call a synapse to what we call the lower motor neuron, which comes out and goes into the nerve, for instance, of your arm or your leg or into the tongue.

• 52:00Speaker 00

  So long skinny cell, is it? It must be quite skinny if it's going down.

• 52:04Speaker 01

  Yeah, we'll talk about microscopic.

• 52:06Speaker 00

  Yeah, microscopic, but altogether, one, one point four metres in length, up to one point four metres. Wow.

• 52:12Speaker 01

  But it controls everything you're doing now, like talking, moving your hands, your leg.

• 52:16Speaker 00

  So it's not your brain that does it, it's the.

• 52:18Speaker 01

  Well, the control is through the brain and central, the central motor neuron is there in the brain.

• 52:23Speaker 00

  Right. And then that's the thing that controls all your motor, motor skills, whatever you want to call it. And, uh, and, and, uh, so just going back a step on that. Um, I remember one of the things I did to my mother is they were, they did it on her hands, they putting pins in it or like, I don't know. Stimulating her hand.

• 52:43Speaker 01

  Yep.

• 52:43Speaker 00

  And that's how she got diagnosed.

• 52:45Speaker 01

  Yeah. So neurophysiology is the critical part of a diagnosis. That's, that's the investigation. And nerves and muscles are electrically active. So the signals going down through the nerve that go to the muscle that keeps the muscle alive. If the muscle, if the nerve is damaged, the muscle starts firing off by itself. And a manifestation of that might be muscle twitching. But if we put a needle into the muscle and it's firing off by itself. So in other words, the patient isn't controlling, it's going, it's just firing, you know, it's going bang, bang, bang, bang, bang. That's a feature of nerve damage to that particular muscle. Now, if for instance, you know, you're working as a butcher and you accidentally cut the nerve and that muscle was affected.

• 53:29Speaker 01

  That makes sense. But if I start putting needles into lots of different areas and getting the same results. It's suggesting there's a more widespread abnormality of nerve and muscle function. And that's what is typically the picture of motor neuron disease. So, so with your mother, it'd be testing muscles in the arms and the legs and the speech muscles. And if they're all affected, that's, you know, that's the sign of motor neuron disease.

• 53:53Speaker 00

  So her first, um, um, sign of there being a problem was that, uh, I, I used to ring her every night. So I'd be going home and on my way home from work, I'd ring her, my mother loves to speak, talk a lot and. She's of Irish descent, so Irish people would love to have a chat. So I would record the moment, I got my car, because I knew it was 25 minutes to get home. So I could sort of limit the time, I said, Mum, I'm home now, I've got to have my dinner. So, but I noticed, she didn't drink. I noticed that she started to sound like she was drunk, not drunk, but slurring her words like a person who'd been drinking would sound, not bad, but just a little bit slurring. And she was always very articulate, but, and I said to her, are you drinking, like having a whiskey with dad or something like it?

• 54:38Speaker 00

  And she said, no, no, no. And then that's when we decided to get her checked out.

• 54:45Speaker 00

  Does it normally start off in the speech?

• 54:49Speaker 01

  So there's three areas really where it begins. So it's usually upper limb onset is the most common, so in your arms. Then lower leg, so leg weakness is the second and speech is the third. So we call it bulbar onset, so it's the tongue muscle, so the tongue has become weak.

• 55:05Speaker 00

  So she would have had those other things before?

• 55:07Speaker 01

  Well, didn't necessarily, it can begin.

• 55:09Speaker 00

  I- in the mouth?

• 55:10Speaker 01

  In the mouth.

• 55:11Speaker 00

  Yeah.

• 55:11Speaker 01

  And I suppose it's interesting that humans are the only ones who have a form of communication like speech. And that's also an area, that's where motor neuron disease begins. Another area where it begins is the pincer grip in the hand. And we're the only mammalian species who can do a pincer grip. But then when you look at the motor strip in the brain, the two biggest areas, they have massive representation of the bulbar region and the thumb and the index finger.

• 55:36Speaker 00

  The bulbar region is the mouth, that's.

• 55:37Speaker 01

  Yeah. So, so that's been evolution. Our brains have grown in those regions so that we can speak, we can do this pincer grip. But as a result, it's got huge metabolic demand. And when there's a failure of that network, how does it manifest? Speech goes off or upper limb function, particularly pincer grip is diminished.

• 55:57Speaker 00

  So has the disease got something to do with the metabolic demand not being satisfied?

• 56:05Speaker 01

  Yeah.

• 56:06Speaker 00

  Or is it? Let's, let's rule genetics out. Is it, is it because metabolic demand is not being met? In other words, I'm neither, not enough bud fling there, but not enough nutrients getting in there. What is it?

• 56:20Speaker 01

  Most likely that is the case. And there's a probably a threshold, what, what gets something over a threshold for an abnormality? And it's probably cellular failure. And that leads to a protein abnormality, a folding protein abnormality. In this case, TDP forty three. Um, and that's then the, the, we use the word nidus, it's the origin. And then the origin starts to spread out like, like a fire spreading through the brain or through the motor pathways.

• 56:47Speaker 00

  And are there any treatments yet?

• 56:51Speaker 01

  Well, in terms of why, why individuals get it, we know that there's genetic abnormalities. And there's been large studies, there's been one study that was done here in Australia and, and in Japan and Korea. Showing that there needed to be six things to happen for someone to develop motor neuron disease. Six hits. And if there is a gene in the family, that accounts for three of the hits, then the other three are at this stage unknown. But if there is a genetic abnormality, there's now genetic treatment. So Tefoson was approved in May of this year, twenty twenty six. That's now available to treat superoxide dismutase one, SOD one genetic forms of ALS.

• 57:35Speaker 01

  Then we have neuroprotective therapy. So really Zola's available. Um, and that was through clinical trials that we were actually part of in the mid nineteen nineties. And that was approved in Australia in twenty twenty five, uh, two thousand and five. And the second medication is a Daravone or Radicava, which is an intravenous infusion. And that was approved in twenty twenty five. So they're the three approved medications in Australia.

• 57:57Speaker 00

  Once you've got it.

• 57:57Speaker 01

  Yeah.

• 57:58Speaker 00

  Yeah, you, you, so it's, and, and what's, and what's its success rate, like efficacy in terms of?

• 58:03Speaker 01

  Well, the idea is to keep people in the milder forms for longer. And so patients are living with the disease for a longer period of time, less affected.

• 58:12Speaker 00

  Right, right. So. But you mentioned with some forms of dementia that there are lifestyle factors that can improve dementia, other lifestyle factors can improve.

• 58:23Speaker 01

  Well, some of the factors are still relevant, but you know, in physical exercise, but not too, too much. And there has been, I suppose, an understanding that sports people are more commonly affected. So for instance, in America, it's called Lou Gehrig's disease. Lou Gehrig developed ALS in his 30s. And obviously, we've seen a lot of tennis players, Brad Drury, Peter Doohan, we've seen rugby players have been affected. So this.

• 58:53Speaker 00

  AFL.

• 58:54Speaker 01

  AFL, Neil Danaher, who's totally, Neil Danaher and Fight MND are the third largest funders of motor neuron disease research globally. Like, isn't that amazing?

• 59:04Speaker 00

  From Australia. Neil Danaher and who's the other?

• 59:06Speaker 01

  Fight MND, which is what he established.

• 59:09Speaker 00

  Yeah, right. Wow.

• 59:10Speaker 01

  Third biggest in the world.

• 59:11Speaker 00

  In the world?

• 59:12Speaker 01

  Yeah. It's amazing.

• 59:14Speaker 00

  That's fantastic.

• 59:15Speaker 01

  Yeah, it's fantastic. So.

• 59:17Speaker 00

  But what are the, some of the lifestyle things that Matthew like?

• 59:21Speaker 01

  Well, these are complicated discussions, but certainly we know that head injuries form part of that discussion. And there was a study that came out a couple of years ago showing higher incidences of neurodegenerative diseases, including motor neuron disease in contact athletes, particularly professional, like high level contact athletes.

• 59:40Speaker 00

  Like NFL and stuff like that?

• 59:42Speaker 01

  Yeah, yeah, yeah. And, and I think that the study came, I think, from the Scottish Brain Bank. So they had a lot of Scottish rugby union players and they, they made that connection. It's similar here. And, and I know that the rugby codes are very interested and are very concerned about it. And they're putting a lot of focus on it in the AFL and the NRL to try and understand these conditions better. But it's a form of research. So we still don't have, you know, a hundred percent diagnostic approach for chronic traumatic and cephalopathy.

• 1:00:12Speaker 00

  CTE.

• 1:00:13Speaker 01

  And, and part of that is really diagnosed by doing the postmortem examination.

• 1:00:19Speaker 00

  Maybe you could explain it because a lot of people come and say, I've been, I've heard them, I know them. I've been diagnosed with a CTE. And as I understand it, you can't do that until you you actually get a hold of their brain once they passed away to do the actual diagnosis.

• 1:00:32Speaker 01

  That's exactly it. And every every approach that's been used up till now has been unsuccessful. And in whole groups where people have said, oh, there's a C T and they go into the, you know, personal examination, there's no neuropathological evidence of C T.

• 1:00:45Speaker 00

  Maybe you could explain what it looks like. I've seen it because I've been to the brain bank at a

• 1:00:49Speaker 01

  Yeah.

• 1:00:49Speaker 00

  Um, a brain and mind center.

• 1:00:51Speaker 01

  Yeah.

• 1:00:52Speaker 00

  And in fact, I made a big donation at them and said to them, they can have my brain when I pass away. Um, if they want to do any value, but they showed me one. It was actually like a, so here's the brain, like, you know, it's sort of wrinkly sort of thing. And there was a a big sort of dent like that. Is that, is that, am I right?

• 1:01:11Speaker 01

  Yeah. So look, there are holes in the brain where fluid passes through and they become bigger. And the cell, the cell processes of the brain become smaller. So they shrink. So you get shrinkage of different areas. You can also get then, it's like scar tissue building up in the brain. Um, and the spaces become bigger. That's, and then there's certain patterns.

• 1:01:31Speaker 00

  But why can't you look at that under an M R I or a machine?

• 1:01:35Speaker 01

  Well, there's so many other things that could also be affecting the brain.

• 1:01:38Speaker 00

  Right.

• 1:01:38Speaker 01

  I think though, that it's really interesting that I think we're going to get better by using the technology of the day. So A I with hundreds of thousands of scans is much better than you or I looking at a scan and saying it looks normal or it doesn't look normal. Like that, that's, that's where we're at today. That's all going to be a thing of the past.

• 1:01:58Speaker 00

  Like the guys from Harrison A I, those guys who, who are producing all these, um, like A I models.

• 1:02:03Speaker 01

  Yeah.

• 1:02:04Speaker 00

  To assist the radiologist.

• 1:02:06Speaker 01

  Yes.

• 1:02:06Speaker 00

  And the neurologist, in your case, uh, in his, his or her diagnosis.

• 1:02:11Speaker 01

  And that, that's a global approach. And at Neuro, we're hopeful of signing up a partnership with I med and using the, the sort of the volume of practices they have to use A I technology to better diagnose all of the conditions we've been talking about, you know, today. And that's going to be the reality. But then also, can we, can we go earlier? And at the moment, we can't, but let's say we did a brain health check of a thirty year old, we wouldn't do an MRI scan because what are we going to find? And what we don't want to do is find an incidental finding. Let's say there's a little cyst in the brain. What should we do about that? And the current understanding of incidental findings is leave them alone. Like that just leads to a whole, you know, you mentioned anxiety and you imagine

• 1:02:54Speaker 01

  the anxiety of the patient, of the treating doctor, of the family. Do you intervene or not? And no, the answer is do not intervene, leave it alone. You didn't do the scan to find that. That's an incidental finding.

• 1:03:05Speaker 00

  But maybe you do go back in five years' time to see if there's been any change.

• 1:03:09Speaker 01

  Exactly. I like your delta. That's good.

• 1:03:12Speaker 00

  I didn't want to use it, but yes.

• 1:03:13Speaker 01

  That's exactly it. Yeah.

• 1:03:15Speaker 00

  Because as you know, I had a prenewvo and the only reason I had it was not to get, I did take it to you and I took it to Live Special, I took it to everybody, but everybody was said, fine. But the point being here is now prenewvo is here in Australia. I mean, I can go and get another one. And I presume they've got their own AI systems now they could probably look at both of them. But I can, someone can, they can say, well, that has grown. So like, one of the things you pointed out to me in relation to the scan of my brain when I had my whole body done, was I think you said, I think you use the word plaque, like be used as normal because for my age. But if that was like double in a year or two, then you say, well, hang on, let's have a look at that.

• 1:03:57Speaker 01

  It's the volume load. Yeah. And that could be getting past the threshold to intervene.

• 1:04:01Speaker 00

  Yeah. Yeah. So I'm actually going to go and get another one. But I think down in Melbourne, but it's, but what do you think about, I mean, I know it's expensive and you know, it's easy for me to say, but what do you think about those sorts of processes as a brain doctor? Us getting, you can get it on your brain for much cheaper than a whole prenewvo. But what do you think about people doing that as a market, say at six years of age? Should they think about that sort of stuff?

• 1:04:33Speaker 01

  Well, look, I'm a scientist and I love the brain. Yeah, I love all of this sort of stuff.

• 1:04:37Speaker 00

  Are you a scientist first or a clinician? What are you?

• 1:04:41Speaker 01

  I'd say clinician.

• 1:04:42Speaker 00

  You're a clinician, as in you diagnose and examine and prescribe?

• 1:04:47Speaker 01

  But we all want, we all want better outcomes. And where's that going to come? That's going to come from the science.

• 1:04:51Speaker 00

  And I think you need to explain that, though. I don't, I think most people don't know the difference between a brain scientist, a neuroscientist and a neurologist. I mean, what are the different roles? And they know different things.

• 1:05:03Speaker 01

  True. Well, look, um, I suppose a neurologist, a neurologist is, is a doctor. So you do, you do medical training. A scientist does a science degree and they might focus on neurosciences. And they might focus on a part of neuroscience. It could be synapses, it could be on the pure mathematics, it could be on structural. But I think, um, it's, science unlocks the understanding. And at the beginning, we talked about brain, you know, being the number one. We were careful about saying, well, you know, you know, cause of death in Australia. But to try and turn that around, we need people focusing on the science of why has that happened? And that could be anything from epidemiology, population studies, what's happening in, you know,

• 1:05:46Speaker 01

  Sydney compared to Perth versus rural Australia. That's all science. And then by trying to take that forward, to try and have a message, to try and improve outcomes, ideally outcomes for a population, but then also outcomes for an individual.

• 1:06:03Speaker 00

  Are there any exciting,

• 1:06:07Speaker 00

  maybe a tablet or whatever it is, exciting things on the, uh, you know, out there in the future that you know of, um, that you guys might be looking at, like, um, testing or whatever the case may be, uh, for things like dementia. M and D, we'll just leave, meningitis, we'll leave aside, but what about dementia?

• 1:06:25Speaker 01

  Well, look, I think one of the most exciting things that's happened in medicine over the last few years has been the GLP-1, so glucagon-like peptides. And these have come out of particularly the realm of sugar control, blood sugar, diabetes. And they're just so incredibly effective.

• 1:06:44Speaker 00

  GLP-1 being Ozempic, for example?

• 1:06:46Speaker 01

  Yeah.

• 1:06:46Speaker 00

  Or Manjura, whatever it's called, those, those things.

• 1:06:49Speaker 01

  So it actually came from very interesting research showing that if you put, if you had glucose, either you ingested it or injected it. They had different levels in the body. So it turns out if you ingest it, there's something was released that actually brings the blood sugar levels down much better than if you had sugar in injected. And it took a while. They worked out it was called glucogen like peptide, so GLP, GLP one. But GLP one only survives in the body for a few minutes after you eat a meal.

• 1:07:20Speaker 00

  Oh, really?

• 1:07:20Speaker 01

  Yeah, so it's not really.

• 1:07:22Speaker 00

  The stuff you produce?

• 1:07:23Speaker 01

  Yeah.

• 1:07:24Speaker 00

  Yeah.

• 1:07:25Speaker 01

  Well, it turns out there was this endocrinologist and he's working for the Veterans Affairs and they said, look, go and, you know, try and work on this area in general. And so he just went through virtually like encyclopedias and he found this thing called a Gila monster. And a Gila monster had pancreatic overgrowth, but also could slow their metabolism down and manage blood sugar control. And so he off, off line, he went and found some of the venom of this Gila monster and then he analyzed.

• 1:07:52Speaker 00

  It's an actual animal?

• 1:07:53Speaker 01

  Yeah, G I L A. And he found a new substance called extendin. And extendin looked like glucagon like peptide. And he thought this is, this could be the key. So he went back to his bosses at Veterans Affairs and he said, look, I think I found something. And I said, look, it's not relevant for us because we're only interested in veterans, more interested in, you know, blast damage, spinal cord injury. We're not interested in this sort of stuff, but he thought he's on to something. So he patented it himself. Um, he had to put a, uh, take a loan out on the house. And then, um, basically it was becoming very, very expensive. So he then went and presented at the American Diabetes Association. And a person from a small therapeutics company, Amalan, came along and thought this is fascinating.

• 1:08:38Speaker 01

  Called up his bosses that, that straight away. And they came up to a licensing agreement that was eventually then taken on with Lily. And that is the whole GLP one. So extendin would turn GLP one instead of disappearing within a few minutes. Could make it last in the body for hours, four to 24 hours. And this all came from this Gila monster, a lizard. So I suppose that also shows discoveries come from anywhere, but you've got to have the curiosity. The curiosity, like this guy thought, oh, that's interesting. There's, there's a lizard that has a big pancreas that must be doing something about, you know, blood sugar control. And that's where it's all come from.

• 1:09:16Speaker 00

  And where does GLP-1 fit into brain health?

• 1:09:20Speaker 01

  Yeah, I got distracted there for a little.

• 1:09:21Speaker 00

  No, but it was a great story. I love it.

• 1:09:23Speaker 01

  But what what's very interesting is that GLP-1 was used for blood sugar control. And in the studies that, and this is all, you know, published in the best journals of the world, New England Journal of Medicine, Lancet, et cetera. They're also now seeing that cognitive function is improved in in diabetics treated with these this family of medications. So that's established. So if you have altered blood sugar control and you get treated with these medications, you preserve brain health. As opposed to not having the treatment. Now, the next question is, okay, they're in diabetic patients. What about patients with Alzheimer's disease? Yeah. And so that's cutting edge now. So the trial's underway in Alzheimer's disease with GLP-1. And I think this is where it's really going to start breaking open.

• 1:10:07Speaker 01

  And again, we're going to see the importance of metabolic health, brain health, frailty, all coming together. But then the individual GP is going to be able to unlock all of this with the markers coming from the patient. So it's going to be fascinating, but I think it's going to, you know, really improve our outcomes as a community.

• 1:10:24Speaker 00

  So is so, but and GLP-1 like originally was marketed. Or is that because originally marketed for people like a lot of people usually lose weight and not originally, but like after that, but when it got into the consumer world, the retail world.

• 1:10:38Speaker 01

  Yeah.

• 1:10:38Speaker 00

  And and how does it stop you from putting weight on? What's it make? I thought it'd stop your appetite or something.

• 1:10:45Speaker 01

  It does work on appetite, but it also works on emptying of the of your stomach of food. But the effects through brain health are also linked to the effects on obesity, reducing inflammation, reducing sleep apnea. And when you have less sleep apnea, the glymphatic system is working, it's clearing out the proteins at nighttime. So it's all, we're all a huge ecosystem.

• 1:11:09Speaker 00

  Okay. And and that's my final question or my final sort of subtopic I wanted to talk about was sleep.

• 1:11:16Speaker 01

  Yeah.

• 1:11:20Speaker 00

  Everyone sleeps, we all need different levels of sleep. Um, and of course, everyone keeps saying you've got to sleep from seven, eight hours. But I mean, it's rare that I ever do that. I might be in bed for that long, but I might not sleep that whole period. What is the difference between, well, why is it important from a brain, from a brain health point of view, um, to A, get overall enough sleep, but B, consistently, um, to do it? And C, also to have, um, slow wave sleep or what they call, you know, deep sleep or restorative sleep, not, not so much rest, but the other one. What is that doing for our brain?

• 1:11:57Speaker 01

  So this is again, an evolving era of science, but understanding that there are systems in the brain that switch on when we're in sleep and, and deep sleep. And we need that every day to clean out the abnormalities, the protein abnormalities in particular. And we've talked about amyloid tau, but presumably TDP 43, alpha sonuclean, they're being pushed through this sort of cleansing process during our sleep. Now, the question, I suppose, when someone does have a sleep abnormality, is, is it a sleep abnormality that's been driven by brain function? Or is it just a lifestyle problem? And it's much better to try and address that early on. And we all need proper sleep and whatever that hour, those hours are, is everyone's different. Like you said, you know, you don't need eight hours and, and that's true.

• 1:12:42Speaker 01

  Some people need five, six, seven, but we all need a certain quality, a certain amount of sleep, but also then a deep sleep. And this is for preserving brain function.

• 1:12:52Speaker 00

  And deep sleep, during that deep sleep period or the slow wave sleep, the deep sleep, when you're sort of basically paralyzed.

• 1:12:57Speaker 01

  Yeah.

• 1:12:57Speaker 00

  You don't, you're not moving, you know, nothing's going on.

• 1:12:59Speaker 01

  Yeah.

• 1:13:00Speaker 00

  As opposed to when you have your own sleep. During that period, um, something opens up in your brain and sends something out there to flush. I mean, unless you get into that state, you don't flush out your brain. Um, is there a general rule as to how many hours per night? Or how much of a, as a total percentage of your total sleep you should be getting?

• 1:13:21Speaker 01

  So a rough sleep hours is like cycle is about three hours, so two of those, so about six hours.

• 1:13:27Speaker 00

  Right.

• 1:13:27Speaker 01

  And probably maybe some break in between. So in and around six hours is the perfect. But obviously we're talking about adults, the younger you are, the more you need. And, you know, children need more eight, 10, et cetera. So I think part of it is to try and ensure that people are used to, uh, looking after themselves to go to sleep, to like sleep hygiene.

• 1:13:49Speaker 00

  Yeah.

• 1:13:50Speaker 01

  It's just so critical.

• 1:13:51Speaker 00

  Yeah. Whilst you're sleeping too.

• 1:13:52Speaker 01

  Yeah. And that's why, again, exercise, making sure you get a bed when you're fatigued.

• 1:13:57Speaker 00

  No booze.

• 1:13:57Speaker 01

  No booze, don't drink, you know, tea and coffee just for beforehand.

• 1:14:01Speaker 00

  Yeah, try to stay on, keep your excitement levels down.

• 1:14:05Speaker 01

  I think you should write a book on all of this because you've got all of the keys.

• 1:14:07Speaker 00

  Can I, can I just ask you one more question and hopefully it's a, something you can comment on. Um, a lot of people I know, a lot of guys I know, um, older, more my age, more my age category. For many, many years I've been taking enormous and all sorts of those old school sleeping tablets. And some people I know are, and I'm one of them, are, uh,

• 1:14:33Speaker 00

  are quite aware and alert when they're sleeping. So they don't get into their deep sleep for as long as other people do. Because maybe because they're listening or they're not listening, but sort of instinctively they're listening. That any little noise will wake them up, any movement will wake them up. They're aware, but they're asleep, sort of thing. And I'm one of those people. And recently I come across, um, um, these sleeping tablets, they're not sleeping tablets. These tablets which actually block the receptors for orexin.

• 1:15:03Speaker 00

  In your brain. And, uh, and I, I just wonder if there's, you wouldn't, might, wouldn't care to make comment on an office area you even looked at, but, um, orexin's the, uh, molecule in our brain that's sort of, just for the audience, it keeps us sort of aware and awake. It's, it's, yeah, sort of a waking. It's, normal sleeping tablets sort of sedate you. They sedate your whole brain and you basically feel like shit when you wake up because you didn't really sleep. They knocked you out. Whereas these things block the receptors on your, on your brain cells that actually look, grab this orexin stuff that keep, that actually is trying to keep you awake. So it sort of blocks that, that process. What do you think about those sorts of tablets? And have you, have you, have you had much experience with it?

• 1:15:48Speaker 01

  Well, what I would say is, again, when we're talking about upstream and downstream, there are lots of other things that happen. So like, we're, we're being very interested in orexin producing cells in the hippocampus because they also control our eating behaviour and they're affected in frontotemporal dementia and motor neuron disease. So, so work that's been done here in Sydney, particularly, uh, Rebecca Ahmed is showing that those cells are affected early in frontotemporal dementia and motor neuron disease. So although you've taken the approach from the orexin to sleep, it's also important for your eating behaviour and-

• 1:16:21Speaker 00

  To have, to control the amount of orexin or?

• 1:16:24Speaker 01

  Yeah, yeah.

• 1:16:25Speaker 00

  That's interesting.

• 1:16:25Speaker 01

  Yeah. And they can, they can degenerate. And when they degenerate, that's why people start having altered eating behaviour. So there's a propensity with certain dementias to like sweet foods and, you know, to eat chocolates and patients typically become, put on weight and, and become obese, don't do exercise. And that's markers that this could be frontotemporal dementia. So what I'm saying is you focus on orexin for sleep, but those orexin cells also have other functions. So that's why I'd be always careful in doing things that might alter function of, of cells in the brain.

• 1:16:58Speaker 00

  Cause orexin is from the Greek word orexie, which means, uh, we say, when we, when we're saying to someone, um, uh, bon appetit, in Greek it's kalorexie, which means good appetite.

• 1:17:10Speaker 00

  And it's funny, so now I know why.

• 1:17:13Speaker 01

  That's fascinating.

• 1:17:14Speaker 00

  Now I know why they they call it a rexin.

• 1:17:16Speaker 01

  Yeah.

• 1:17:16Speaker 00

  It has something to do with your appetite.

• 1:17:18Speaker 01

  It does, and and eating behaviour.

• 1:17:20Speaker 00

  Oh, right.

• 1:17:21Speaker 01

  Yeah.

• 1:17:21Speaker 00

  So would would you expect then if um, you know, let's say the half life of a rexin pill was twenty four hours, right, I'm gonna say, this is probably not the case, but um, that you might lose your hunger.

• 1:17:34Speaker 01

  I would say so.

• 1:17:35Speaker 00

  Yeah.

• 1:17:35Speaker 01

  And the other thing is, though, I presume that it bounces back because.

• 1:17:38Speaker 00

  It does have a bounce. There's a mad bounce because I've measured it.

• 1:17:42Speaker 01

  Uh huh.

• 1:17:43Speaker 00

  So I measured, I measured heart rate and um, H R V. So, and I've watched it go through my, so I look at my, I go through and I'll look at my, my um, movements of my heart, my heart movements, because it records everything. And you sleep deep in the beginning, but there's a bounce because the half life actually is five hours. So.

• 1:18:04Speaker 01

  Right.

• 1:18:05Speaker 00

  Towards the end of the sleep period.

• 1:18:07Speaker 01

  Yeah.

• 1:18:07Speaker 00

  Your heart rate shoots up big time and your H R V drops big time.

• 1:18:11Speaker 01

  Yeah, yeah, well, it's right at the core of of functions in the hypothalamus and then.

• 1:18:17Speaker 00

  You actually wake up really bright. So to some extent, it's a bit of a trap because you think this is a sleeping tablet. And when I take this sleeping tablet, I wake up and feel really good. I feel really awake. Whereas if I take a a normal, a normal, you know, the usual types of sleeping tablets, I wake up and I feel like shit. So immediately that, my brain says to me, well, that's better, that's good. But the reason is because my erection bounces back the other direction and I'm actually wide awake. And I can actually get away with less sleep and feel quite awake. But it's it's it's just a bounce because all of a sudden you, the receptors are now released from, they're not blocked. And they're grabbing everything.

• 1:18:57Speaker 01

  Well, it's fascinating. So presumably ancient Greeks must have known a bit about this.

• 1:19:01Speaker 00

  They probably did.

• 1:19:02Speaker 01

  Yeah.

• 1:19:03Speaker 00

  This ancient Greek does.

• 1:19:06Speaker 00

  Well, I really enjoyed today. I've got to ask you this one question from my friend, if you don't mind.

• 1:19:11Speaker 01

  Monoclonal antibodies.

• 1:19:12Speaker 00

  That's what this is, isn't it?

• 1:19:13Speaker 01

  Yeah.

• 1:19:13Speaker 00

  Right.

• 1:19:14Speaker 01

  So monoclonal antibodies are now approved in Australia, uh, lecanumab, donanumab. And they're very effective at stripping amyloid from the brain. And we know that. So when we do a PET scan, if we do an amyloid PET scan before and after, we can see that the amyloid is either, you know, cleared or the, the, the volume is right down.

• 1:19:35Speaker 00

  Post taking the monoclonal.

• 1:19:37Speaker 01

  Yeah.

• 1:19:37Speaker 00

  Uh, antibody.

• 1:19:39Speaker 01

  But then you may say to me, well, okay, if that's the case and that protein is the critical driver of Alzheimer's disease, the patient should be completely back to normal. But they're not. So, and that, that's where research is at. So we're clearing amyloid, but the patients aren't necessarily getting better. But what's happening is you're slowing the decline. You're turning, you're turning the disease process back perhaps up to three years.

• 1:20:02Speaker 00

  Right, okay.

• 1:20:04Speaker 01

  But cutting edge research, and, and these are patients who have had already manifestations of memory problems, but they're not, they're not too far affected because it's too late. So they have to have a mild, um, effect in their brain function. But the cutting edge then is what happens if we treated people, you know, before they developed the condition? So we're looking at now, this is research that's being underway at, at neuroscience research Australia. And Emma Devaney, I think he spoke to as one of the key drivers of that. So she's, she's treating patients who have genetic, uh, malformations linked to Alzheimer's disease with these monoclonal antibodies in the hope they'll never develop the condition. And already we're seeing that if the families were developing,

• 1:20:45Speaker 01

  say Alzheimer's disease at forty five, fifty, they're passing those ages without developing the condition.

• 1:20:51Speaker 00

  Oh, wow.

• 1:20:51Speaker 01

  Yeah. So it's having an effect, but also these are early generation therapies. So in other words, that's the first type of approach.

• 1:20:58Speaker 00

  There'd be more iterations.

• 1:21:00Speaker 01

  And, and there's so many coming through. Right now, as we speak.

• 1:21:04Speaker 00

  And what are those monoclonal antibodies called?

• 1:21:07Speaker 01

  It's an anamab and lecanamab. So M A B means monoclonal antibodies and they're two different companies.

• 1:21:13Speaker 00

  And they're both basically available through your neurologist if you're a person in this category.

• 1:21:17Speaker 01

  There are people being treated here in Sydney now, so it's approved by the T G A. It hasn't yet been approved by the Pharmaceutical Benefits Advisory Committee.

• 1:21:25Speaker 00

  So you got paid for it.

• 1:21:27Speaker 01

  So, yeah, so a standard, and don't quote me on this, but a standard treatment course would be about a hundred thousand dollars. But if you, if you want to preserve your brain function.

• 1:21:37Speaker 00

  That's worth it.

• 1:21:38Speaker 01

  It's absolutely worth it. Absolutely worth it. If you can tap into your super and use it.

• 1:21:43Speaker 00

  And, and I had one final question for you. Just in terms of, and if I could just go back to cholesterol.

• 1:21:50Speaker 01

  Yeah.

• 1:21:51Speaker 00

  And to the extent that that's a problem for your brain too.

• 1:21:55Speaker 00

  And let's say you're, and I'd like you to comment on this, let's say you're statin. You're not able to take statins, you know, for some reason the statins affect your sleep or whatever the case may be.

• 1:22:08Speaker 00

  And sleep's critical, so. There are now injections you can get. Which actually don't cross the blood brain barrier and like statins do. And, but will reduce, significantly reduce your LDL.

• 1:22:25Speaker 01

  Yeah.

• 1:22:27Speaker 00

  Would you just like to comment on that?

• 1:22:28Speaker 01

  Well, we were just talking about monoclonal antibodies. So monoclonal antibodies actually came from hematology for cancers. They're very effective in melanoma. We're now putting them into the brain for Alzheimer's disease. They're also very, very effective for cholesterol control. So monoclonal antibodies are available for lowering cholesterol. But obviously that needs to be under pharmaceutical benefits scheme. There are certain people who are entitled to it and not, and there are markers. It's not really my area, but there are people who focus on that.

• 1:23:00Speaker 00

  But if it works.

• 1:23:01Speaker 01

  It does work. It's very effective.

• 1:23:02Speaker 00

  And, and if it's effective, if you can get your cholesterol down to the levels where it's, you know, like in the right territory.

• 1:23:08Speaker 01

  Yeah.

• 1:23:09Speaker 00

  Then it's good for your brain.

• 1:23:10Speaker 01

  It's fantastic for the brain. And again, that's going to be transformational for our community. Like that's, that's, that's an amazing development.

• 1:23:17Speaker 00

  Yeah, I'm about to try it. But I'm not, I'm not someone to qualify as under the pharmaceutical benefits scheme. I have to pay for it.

• 1:23:24Speaker 01

  Yeah.

• 1:23:24Speaker 00

  It's not cheap. Um. But you have to go, I think, two injections a year. You can do one where you just do it every week or whatever it is. But there's another one where you get two injections a year. But allegedly it reduces your LDL by fifty percent. Quite quickly.

• 1:23:37Speaker 01

  Incredibly effective.

• 1:23:38Speaker 00

  Yeah, it activates more receptors to grab hold of more LDL.

• 1:23:42Speaker 01

  Right.

• 1:23:42Speaker 00

  Because there's something in your system that turns on, that blocks these receptors. What they do is they stop that, I think it's PCSK or nineteen.

• 1:23:52Speaker 01

  Yep.

• 1:23:52Speaker 00

  Is the name of the, you know, the molecule. And that turns, it stops that, it turns that off. And then your receptors are grabbing all the LDL they can on your cells.

• 1:24:02Speaker 01

  Wow.

• 1:24:03Speaker 00

  And that, and that's, this injection just fixes that part. So it goes nowhere else. Just go straight there and sorts it out. It's pretty amazing and great science. And again, some scientists have worked this stuff out. They probably were doing it with some, using it for something else at some stage. And all these things, as you say, you always say, and I want everyone to remember this, that what's good for your heart is good for your brain.

• 1:24:25Speaker 01

  Fantastic.

• 1:24:26Speaker 00

  I'm never gonna forget that. Matthew, thanks very much.

• 1:24:28Speaker 01

  No, thanks, Mark. And then thanks for your support for brain health, mental health, and then also for neuroscience research Australia. We're really grateful. So thank you.

• 1:24:35Speaker 00

  You're most welcome.