 So to introduce myself, my name is Anik, I have worked at the Brain Foundation for three years and I'll be your host tonight. I am the grants program manager and digital lead, which means that I oversee the grant application process and coordinate with our scientific advisory committee to get all the research grant applications marked. I also write a lot of the content for the Brain Foundation and our division Migraine Headache Australia. We also have Carl Sinanato moderating tonight, so you will see him in the chat as moderator Brain Foundation. So for those of you who are new or who don't know much about the Brain Foundation, here's just a bit about what we do. Our mission here is threefold. So our primary goal is to fund the highest quality Australian research into brain diseases, disorders and injuries. And this research can help improve diagnoses, treatments and patient outcomes overall. And the Brain Foundation was actually established in 1970, so we've been doing this for 53 years now. Secondly, we provide medically reviewed resources about brain conditions that anyone can use to learn about a particular disorder. This includes articles on our website and also content like this webinar or the videos that we'll be releasing throughout Brain Awareness Week. Lastly, we raise awareness about the impact of brain diseases and advocate for patients. And this is a really important part of our mission and one of the reasons that Brain Awareness Week exists, because without people being aware of the impact of brain diseases on Australians, their loved ones, the medical system, it's really hard to get support for research and that exists at both the general public and also importantly at a government level as well. So advocacy is a really important part of what we do. So just make sure that everyone's in the right place. Who is this webinar for? If you are interested in learning about how to improve your brain health, if you want to understand more about dementia and also if you want to ask questions to a brain researcher about the link between health, lifestyle factors and dementia, or any other questions about brain health and the aging brain as well. So I'd like to introduce our speaker for tonight who is Associate Professor Greg Sutherland. Greg is the director of the New South Wales Brain Tissue Resource Centre and an Associate Professor of Pathology at the University of Sydney. And the Brain Tissue Resource Centre is actually a brain bank, which means that you can register to donate your brain after death. And this is a really important part of medical research and helps enable a lot of really groundbreaking research projects. Greg also leads the Brain and Body Research Node, which aims to understand the relationship between the brain and systemic chronic disorders. So that includes things like obesity and diabetes. And so basically they work to understand how whole body health and brain health affect each other. Greg's research interests include neuropathology, which is the study of diseases affecting the nervous system, transcriptomics, which is the study of DNA and the genetic epidemiology of neurodegenerative diseases. So epidemiology is the study of how often diseases occur in different groups of people and also why those people get those diseases. So without any further ado, let's start the webinar. Hello. Welcome to a talk on brain health and aging as part of Brain Awareness Week in 2023. My name is Greg Sutherland. I'm Associate Professor of Neuropathology at the University of Sydney. And I work in this building here, the Charles Perkins Centre. What we're going to talk about today is brain health, what it means. And particularly the relationship of healthy brain aging and how that is distinguished from dementia, which is the common form of disease that we see associated with brain. I'd also like to talk a little bit about busting some myths about what might and might not cause dementia. Talk a little bit about my dementia research and then give a few basic healthy brain tips to finish off. I'm sure you'll agree that there's a lot of conflicting information out there about how you can defy the odds and have a healthy brain right up to the end of your life and in particular avoid things like dementia. This is some stories taken from Neuroscience News website. There's a couple of suggestions. One of them is sleep medications, the likes of still knocks and Christian Charles with dementia. And over here we've got one talking about oral health and how that might contribute to dementia. As it turns out, neither of these suggestions is a major factor, at least in my opinion on what causes dementia. But they're both quite interesting things to follow up because they may give us clues about what are important mechanisms because they have some sort of modified effect on those mechanisms. So the human brain is absolutely unique for our size relative to even large animals. Our brain is immense and particularly one part of our brain called the forebrain. You look down here at our friend, the mouse is used in the majority of animal model experiments that we do in medical research. They've got a very small frontal lobe whereas it's large in humans. It's so large that it needs to be folded up on itself. And you can see these folds here. This is a fixed brain taken from someone after death. And these folds are called gyrie and are separated by these spaces. It just allows a lot more brain for the amount of space. And average size of the human brain is about one and a half kgs compared with, say, a sheep brain. You're looking at 400 grams or only a quarter of the size and all the way down to a tenth of that size of fully milligrams for a mouse brain. Within the brain, at a microscopic level, there's a number of different brain cells. The ones we typically will hear about are the neurons and these are the ones we often concentrate on when we think about diseases. But there are a lot of other cells, oligodendrocytes, for example. They have the myelin within them that is responsible for insulating axons or neurites or parts of the neuron where information travels up and down and they allow that to travel faster. Astrocytes are supporting cells and they do a lot of mopping up of neurochemicals and getting them back to the neurons. But have a lot of other roles that some of them we don't quite understand. And there's also these cells called microglia. These are immune cells or the brain's resident immune cells. And as we'll see with dementia, a lot of the gene variants that have been associated with dementia are actually the protein products of those genes are expressed in microglia. So the biology of microglia is becoming more and more central to understanding dementia and Alzheimer's disease. And it's something that my lab works on. Now, in the preceding schematic, we were able to see a lot of space around these cells in the brain, but that is purely a schematic. In reality, the processes of cells like neurons and blue, oligodendrocytes in red and astrocytes in red and also microglia and green, their processes are not only tightly woven within each other, but also communicating. And so that space between the cells or that open space between the cells in reality doesn't exist. It's just this bird's nest of processes within the human brain. And on the right hand side, in red, we have something that occurs in Alzheimer's disease brains called plaques. And when you throw in pathology into the mix and the situation becomes even more complex. In green here, we're looking at those immune cells of the brain called microglia. You notice they've got quite a distinct shape to what's shown over on the left. They're reacting to this particular plaque in a quite sort of chaotic fashion. And it's this type of scenario that a lot of my research is focused on trying to understand how and why cells respond and whether we can either, if it's good response, augment it or if it's a bad response, try and stop it or slow it down. So what is brain health? Well, brain health and particularly aging brain health is to have no serious injury or disease affecting your brain over your lifespan. Brain health can sometimes be just thought of as whole body health. We're starting to understand that many diseases that we thought were just associated with the brain had a whole body aspect to them. Although there are other diseases that seem to just affect the brain. So brain health is really a situation where you would avoid the causes of an unhealthy brain. If you can't avoid them, we would talk about factors being modifiable. But there's other factors that you can't avoid, like your own genetics. But some examples of causes of brain disease that you might be able to avoid or include infectious causes. This is a disease called Croats of Yakob disease. It would be quite difficult to avoid that. Evenologically, similarly, a disease called multiple sclerosis, cells, lymphocytes, cross into the brain and cause problems with the white matter. Vascular, we're going to talk a little bit about today. It's also known as Strokes. Traumatic, head injuries or repetitive head injuries. Neoplastic gliomas, major problem for the cancer world because the success rate of treating gliomas has not improved over a number of years. Metabolic toxic, alcohol being the most commonly used and abused drug. Something that my lab also works on. Alcohol affects the brain. Degenerative, the dementias that we're going to talk about today. Notice that this is the same disease, multiple sclerosis, as the immunological group. But what happens in multiple sclerosis, as I said, is lymphocytes cross the brain and start attacking the white matter or demyelination. So multiple sclerosis fits both of those categories. Of the leading causes of death in Australia, two out of four actually affect the brain, dementia including Alzheimer's disease and cerebrovascular disease or stroke. Currently heart disease for men and women from when statistics began in the earlier 20th century has always been the number one killer in Australia and most Western countries. But in the last set of statistics in 2020 was the first time at least for females where currently heart disease was displaced from the top category and replaced by dementia. And for most of you, and for me this came as a surprise because we usually think of dementia as just affecting the aged population and maybe not being that common. But as it turns out with an increasingly older population in Australia and most countries in the world, dementia is almost reaching epidemic proportions. These statistics might change a little bit in the next iteration because of COVID, but in general brain diseases, chronic brain diseases, dementia and stroke or cerebrovascular disease are two of the biggest causes of death in Australia. The risk factors for stroke and the risk factors for dementia overlap to some degree. Both of them share the major risk factor as aging. And as I just said, we have an aging population so both of these diseases are on the increase. Other factors that cause or increase your chances of having a stroke are very much the same as what increases your chances of coronary artery disease or coronary heart disease or just heart disease because their etiology or what causes the disease is common between both of these types of problems. In fact, things like buildup of fatty streaks or what we call atherosclerosis in your blood vessels. And so cigarette smoking or high cholesterol levels or uncontrolled blood, high blood pressure are both problematic for heart disease and also for stroke. And I'll point out here also that some of those same associations exist for dementia and particularly Alzheimer's disease and age is again the major factor for Alzheimer's disease. Now, why I've talked about probable associations here is that the one aspect of the evidence for these cardiovascular factors is pretty strong. But it also is because there is a reasonably high percentage of Alzheimer's disease cases that also have vascular problems which probably add collectively to people becoming demented or losing their cognitive abilities. The other thing I wanted to quickly point out on the risk factors for AD is that your genetics and particularly a type of gene variant in a protein called Apolypo protein E, the E4 variant of that gene is a major, the second major problem or the second major cause of Alzheimer's disease after aging. So someone who's old and has two copies of this particular gene and therefore two copies of the protein, they are at a much higher risk of developing Alzheimer's disease in their lifetime than people who don't have this particular gene variant. I'll return to that subject a little bit later. There's a lot of research that's been happening in brain aging. There seems to be different aging processes going on in different organs whether it's your skin or your gut or your liver or in fact your brain. They seem to all age at a different speed, but also within individuals. Organs and individuals age at different rates and you would be familiar with this idea of biological aging versus chronological aging. Some people have been appearing biologically younger than their chronological age and there seems to be some evidence that that is indeed the case. And some people's brains look older than would be expected. And this is mostly associated with some of those risk factors like smoking and cardiovascular risk factors I talked about before and the evidence shown by these particular researchers. We know with aging that there are a lot of changes within the brain including within the blood vessels. And we also know that the brain gets smaller or loses volume, atrophies with aging. That happens in both males and females at about the same rate. And we also know and opposite to what was originally thought that we age because we lose neurons or those cells that send signals between them when we think or when we want to make a movement or feel something via touch or one of our other senses. Rather than it being loss of neurons, it actually appears to be loss of white matter that insulating material or myelin that we talked about a little bit earlier. When it comes to neurons, some of the neurons seem to shrink but we don't lose many neurons with aging. Yet the combination of that white matter loss with neurons is enough to give us some degree of cognitive decline as we age. I'm mentioning aging because when it comes to dementia, this as you might have already thought from my previous comments is the rate of or the prevalence of dementia at different ages goes out quite rapidly. So it's very unusual for people under 60 years of age to get dementia. But by the time people are 85 years of age and the average longevity for both men and women or combined in Australia is currently around about 82 or 83, the time people reach 85 years of age about 25% of that age group over 85 will develop dementia. So that's getting to quite a high level. Why do sometimes we use the term dementia and other times use the term Alzheimer's disease? Alzheimer's disease is a type of dementia but it's also the most common type. There's various statistics out there but probably about 60 to 70% of all dementia are Alzheimer's disease or at least mainly Alzheimer's disease. Because if you look down here, you'll notice also that there's a mixed type of dementia where there's a combination of what we typically see in Alzheimer's disease but also with vascular damage. And as I mentioned earlier, some of the reasons why having good vascular health and avoiding things like uncontrolled high blood pressure is because and it can prevent dementia because it mainly has the effect on this vascular component of the disease. It may be some lesser effects on Alzheimer's disease but it probably is mainly through keeping your cerebral vasculature very healthy. These are the hallmark pathologies of AED that we see if we look down the microscope in someone who has demented during their life and died of Alzheimer's disease. We only come to the conclusion that had Alzheimer's disease by looking at these entities at post-mortem. And what we're looking at here is plaques which are made up of a substance, a sticky substance called beta amyloid, tangles which are equally made up of the sticky substance but this time it's a substance called a protein called tau. And then these two things can sometimes come together either with tangles and plaques and sometimes also tangles right within the plaques. When an individual comes through to post-mortem and we see large amounts of these, then they are declared to have Alzheimer's disease. But an important point is that it's not people not only people with Alzheimer's disease that develop plaques and tangles. As we age, the majority of us will develop plaques and almost all of us will develop tangles. So there's a real difficulty here in distinguishing the effects of natural aging and the effects of Alzheimer's disease and that makes our usual experimental paradigm of cases versus controls to try to understand what are the factors affecting the diseased community as opposed to people who don't develop dementia. It makes it extremely hard. Indeed, making a diagnosis of Alzheimer's disease is a probabilistic diagnosis because people who demand get more plaques and more tangles across more of their brain than someone who does not demand. So why does that happen to certain people? Well, we actually do not know. I talked about this genetic variant called apolipoprotein E. There's also other genes that we know and some of those genes, their proteins are expressed in microglia. Diabetes has a small amount of effect. So does being a female. But the biggest effect on whether you develop Alzheimer's disease is whether you live to a ripe old age. So aging is very inherent to why people develop the disease. There's some large gene effects. There's some protective effects like being highly educated or being a male. But in general, there's a lot of factors that we still don't understand. Some of the myths around what will cause dementia arise not so much as myths, but some small studies, and they often are small studies where someone comes up with an idea that a particular habit might increase your risk for Alzheimer's disease. In this case, it's slightly tongue-in-cheek with nose-picking. But what they're making the association is between bacteria that might be found in your nose and that your nose is quite close to your brain. It's separated at one stage by quite a thin bony plate, which has actually got many holes in it to allow your olfactory nerves to travel through. But that's very close to the brain. And the thought being, is it possible that some bacteria can get across and into the brain and cause Alzheimer's disease and what some other diseases like Parkinson's disease. This is known as the infectious hypothesis for Alzheimer's disease. It's been around in various forms over a long period of time. It may have some... It may modify your risk slightly, but it's probably not the major reason why someone gets Alzheimer's disease or other forms of dementia. We recently took advantage of a massive new study that's in the UK. It's called the UK Biobank, where they took 500,000 people and measured everything they possibly could on these people, including doing a lot of survey data. They checked their cognitive function. They imaged them in MRI scanners. And with all of that information and with a few people, because these are aged individuals, having already converted to AD, we tried to work out what was the difference between people who had dementia and people who hadn't. And when we matched them for aging, so took aging out of the equation, the only real thing that we could find or only major effect was the apolipoprotein E4, which we already knew about. There were a few other genetic effects, interestingly, very close to apoE4 in our DNA. That also had a bit of a major effect, but from there, and the red is risk and blue is protective from there, all the others had very, very small effects. And so we weren't really able to find any smoking gun or want of a better word from this particular study. There were some interesting things, the protective effect of insomnia that is quite a controversial thing, but also we saw some liver enzymes that seemed to be increased or at least a ratio of increased could be problematic. Again, this is this idea that maybe some of these brain only or what we think of brain only diseases do affect other organs in the body. And there is something called the brain, liver, gut, microbiome axis that might be consistent with this idea that liver is involved in some of these neurodegenerative diseases. What about alcohol? Is that a risk factor for dementia? Well, heavy consumption of alcohol throughout your life, and I mean very heavy, like 100 grams a day, which would be equivalent to sort of eight cans of beer or more than a bottle of wine. That can be problematic. It would be also problematic for every other organ in your body. But in general, if you're a light drinker of alcohol, it seems to have what we call a J-curve effect on most of the organs in the body. We're a little bit of alcohol compared with people who are staying completely at the positive effect on your cognition. But once you start drinking a lot more, then things go in the opposite direction. There's a condition that we also study called alcohol-related brain damage and people develop cognitive dysfunction. Some other people call it alcoholic dementia. But whether alcohol increases your risk for Alzheimer's disease, if it does, it's probably only has a small effect. So in general, alcohol is not a big problem for dementia per se. But drinking lots of alcohol is problematic for just about every other organ in your body, including your brain, but not directly related to Alzheimer's disease. So what is on the horizon for a cure or a treatment for Alzheimer's disease? Well, interestingly, some types of drugs called amyloid-modifying drugs based on antibodies would bind to and seemingly remove amyloid from the brain. They have been recently in 2020 and again just at the end of last year, these two drugs have now been approved by the FDA to be used in patients. It's a very controversial decision because even though we can see from imaging or a type of imaging called PET imaging that these people lose their amyloid in their brain, both drugs have only resulted in modest improvements in cognitive decline. Both drugs are very expensive, and so a lot of neurologists are loathed to put people on these very expensive drugs if they're not going to have much improvement on their cognition. I think most people would agree whether they're in the amyloid-modifying drug camp or not that adjunctive treatments are required and to have new treatments, unique, new targets. And this is the type of stuff that my lab works on. So how do we go about doing that? Well, very quickly, we're using two techniques that have been developed over the last couple of years. One's called single-cell studies where we isolate cells from people with the disease and people without it dissociating out their brain tissue after their death and then working out whether the cells and people with the disease or not are expressing the same type of proteins. And what we found with this work among others too is that there are actually lots of different types of oligodendrocytes or different types of astrocytes. And the size of the clusters and all the existence of some of these sub-clusters of these different brain cells are different whether you've got the disease or you haven't got the disease. And so what we think happens is that the brain cell type change in people with the particular disease and by looking at those patterns we think we can find new targets for new therapies. A technique that's very similar to that is called spatial transcriptomics. But this time, rather than breaking the brain up to get the information in terms of single-cells we leave the brain tissue as it is, photograph it and then do the transcriptomics so then we can relate what's happening in terms of gene expression directly to what's happening in the tissue including whether there is pathology in that tissue or not. These are some mouse tissue samples that are not human but it gives you an idea of this new approach and this is something that we're really excited about because I think this is going to be revolutionary in terms of our understanding of brain diseases and in fact all diseases. So as a summary, there's two major killers that are primarily regarded as as brain diseases in Australia that's dementia and stroke. Your stroke risk is very similar to your risk of heart disease and other vascular diseases and so trying to reduce the chance of that happening is very much along the lines of don't smoke, control high blood pressure, control bad cholesterol with things like statins, increase your level of physical activity. Dementia is different. Most dementia is Alzheimer's disease and the two major risk factors for Alzheimer's disease are non-modifiable. It's your age and the genetics that you're born with and in particular a gene variant called HOV4. There's also a vascular component although that varies from person to person but stroke avoidant measures or measures to avoid heart disease like I've mentioned just above are going to be useful at warning of dementia in a lot of individuals that can be underestimated. What about cognitive reserve? What about this idea of use it or lose it? Use your brain or lose your cognition? There is some truth in that and it probably emanates from the fact that people who have higher education have maybe developed their brain to a greater extent where it can withstand more pathology before the signs of dementia show but there's no really clear evidence or at least any evidence that you can stop dementia if you have those other modifiable risk factors and it seems just to put this in context that physical activity is probably doing more for you than the mental activity but it's all a little bit relative. What else? Well, that's what we're looking for in our lab and a lot of labs around the world. Our own lab uses human brain tissue and we're also lucky at University of Sydney and the Charles Perkins Center to have a brain bank. This brain bank collects tissue after people have died and you might not be aware that that is a possibility but you can donate your tissue to support research into brain diseases. So just lastly, if you're interested in this work and particularly interested in becoming a brain donor please get in contact with me or my staff at some of these resources. It's a great gift and it's making a lot of difference in the way we do research for future people and the risk of developing some of these terrible diseases. I thank you and I look forward to hearing your questions in the next part of this webinar. Thank you so much Greg, great to have you here. We've got quite a few questions here so let's get straight into it. Our first few questions are about research. So Linda asks, apart from a brain autopsy is there any way to determine if someone has had dementia with Lewy bodies? Yeah, dementia with Lewy bodies is a disease that's quite similar to Alzheimer's disease and in that way there will be similar findings on imaging and also some new blood-based biomarkers. Whether you could tell clinically that someone had DLB from Alzheimer's with any degree of confidence it's hard to say. There are a couple of clinical things that happen with DLB such as visual hallucinations which don't often happen with people with Alzheimer's disease. I think the other thing with dementia with Lewy bodies is that the Lewy bodies give the clue away that these people often have modus symptoms associated with Parkinson's disease. And a rule of thumb is that if you develop dementia within one year of your diagnosis of Parkinson's disease then it's likely to be dementia with Lewy bodies. The variation on that thing is if you don't develop dementia but you do develop eventually they use the term Parkinson's disease and dementia or Parkinson's disease dementia. So we're getting better we're getting better at differentiating between those diseases but there's no real diagnostic test at the moment. And with that research into blood tests once they become available for clinicians just to clarify they'll be able to tell the difference between Alzheimer's disease and Lewy body disease or are they just blood tests for dementia in general? Yeah, I think I think in terms of sensitivity they've got some good tests blood biomarkers that will pick out Alzheimer's disease so by exclusion if you've got a very similar disease to Alzheimer's and you have the general blood markers of a neurodegenerative process then you would probably have one of the other two common types of dementia being that particular dementia or dementia with Lewy bodies so there is a good chance you'd have it but I'm not aware that there is any either cut off with those general markers or specific markers for dementia with Lewy bodies at the moment. Okay, and another question from an anonymous attendee is how much research has been done into cohorts of society where dementia is more common for example people living with Down syndrome. Yes, quite a lot and within with some of the ethical constraints associated with the Down syndrome community but it's an interesting question because people with Down syndrome have three copies or try to assume three copies of chromosome 21 and the gene or the amyloid precursor protein which is cut up to produce the amyloid in our brains both normally and unfortunately abnormally that sits on chromosome 21 so for people with Down syndrome they inherit three copies and it's the inheriting those three copies in excess of the precursor protein that seems to lead to the Alzheimer's disease almost everyone with Down syndrome develops Alzheimer's disease and they tend to develop by about the fourth decade so it's quite a bit quicker than other people so Down syndrome is one of the key bits of evidence that there is a genetic of genetics in Alzheimer's disease and really people started from the knowing about Down syndrome in the trisomy 21 they started looking for gene duplications in people with Alzheimer's disease and in fact they eventually did find some but what they found first were different types of mutations and they were found in the early 90s so work done on Down syndrome was actually critical of starting this and work continues obviously it's very problematic for persons with Down syndrome living with Down syndrome's dementia so they should benefit from similar treatments that benefit the greater Alzheimer's disease community I would imagine OK great thank you so much so a few questions about comorbidities Ben asked he saw that you put trauma on the possible causes of brain disease and they were just wondering are concussions able to lead to dementia and if so how bad is that and how big of a risk factor is head trauma for Alzheimer's dementia so just in terms of Alzheimer's disease it's actually a single traumatic incident rather than this repetitive trauma that we might associate with contact sports that seems to be a risk factor for Alzheimer's disease if you have concussion and multiple concussions you can develop a very similar disease to Alzheimer's called chronic traumatic encephalography Alzheimer's disease and chronic traumatic encephalography or CTE both have built up of a protein called tau or fibroletal in the brains but where the tau builds up is slightly different between the two diseases and you don't get the amyloid build up so definitely multiple concussions probably there's a genetic influence there too it would lead to an Alzheimer's disease or like Alzheimer's disease but not Alzheimer's disease itself but there seems to be a risk associated with traumatic brain injury where you've lost consciousness that seems to show up in studies to be a risk factor for Alzheimer's disease okay, great and another question from Wasfi is if you have treated hypertension would hypertension still be a risk factor or is it reduced once it's treated? I think the simplest way to describe that is treatment is going in control of your hypertension or regulated blood pressure is going to reduce your risk immeasurably there are other issues that may while it wasn't treated or while it's building up there could be issues with some of your cerebrovascular or blood vessels within your brain they may lose a little bit of elasticity but in general if it's under control and I think we're really good at picking up hypertension when I say we do general practitioners if it's controlled it will be reducing your risk quite considerably okay and Crystal asks and also Jessica asks about this as well is there a link between migraine and dementia and also particularly long term migraine sufferers? Not that I know of but thanks for the question it's a very interesting question no, not that I know of that I have never read that that's the case so I don't believe so okay, well that's good to hear for people living with migraine and another question from Alice is what do you think about neuroplasticity and neurogenesis and she also kind of asked this in the context of concussions and head injury, sorry to go back to that but yeah I had a little bit to do with neurogenesis or neurogenesis studies a few years ago we started looking at it because it was suggested that alcohol could cause problems for the brain by depressing neurogenesis so neurogenesis is this idea or at least adult neurogenesis is this idea that neurons continue to be born throughout your life and born but there's stem cells, neural stem cells within your brain in two areas and we looked at that and we didn't find any difference with people with alcoholism but it also was becoming quite controversial what level of neurogenesis was happening in the brain so we actually looked at that over the lifespan of individuals from three months of age all the way up to 60 years of age I think at the time neurogenesis tailed off very abruptly around about three years of age and then continued to tail off from there so our own feeling is that although neurogenesis does exist it's more like a residual almost vestigial process in the adult brain it's not to say it can't be reignited if we understood how to do it so the distinction between neurogenesis and neuroplasticity is neuroplasticity is a much more broader situation and does happen in the brain so two aspects myelination or the insulating fat that sits around our axons that develops as we age well into our 20s and 30s so that's one of the last processes and then there's constant tinkering with the connections between neurons that we call synapses synapses can be removed, they can be strengthened both on a structural level and also within the cells on a molecular level so there is neuroplasticity neurogenesis not so much in the adult brain but we're still trying to work out how we could stimulate it great thank you so we've got a few questions here about general brain health Tali asks is there any evidence to suggest that fish oil supplements are beneficial for brain health and if so is that because of the anti-inflammatory effect yeah fish oil could have two effects it could be anti-laboratives or antioxidants probably it's also a good source of what they call good fats or non-trans fats which the brain requires fatty acids and then tends to make the fats that it needs including myelin but any source of fish oil and any other source of polyunsaturated fatty acids is always going to be good for the brain the exact relationships of what's happening at your gut level what's being produced in your liver and what reaches the brain and then what the brain is able to do with that still is a little bit unknown and it does get offset a little bit by aging in particularly an aging liver however in general those polyunsaturated fats and sources of them certainly would do no harm and are probably a good idea great Adrienne asks on the genetic side of things she asks it sounds like what's your opinion on that do you think that's true or what do you have to say yeah look it's pretty I think it's important to make the distinction between EpoE4 EpoE4 is a variant that around about at least 8% yeah but about 20% of the population carried that variant it's not a mutation so mutations are in three other genes and if you have those mutations you will definitely develop the disease if you have one copy of the variant EpoE4 as opposed to the more common forms EpoE3 then your lifetime risk increases about two fold but if you do have two copies then it increases your lifetime risk at ten times that means if you are a homozygote or you have two copies of EpoE4 then you've got about a 50% chance of developing Alzheimer's disease during your life so I wouldn't say I wouldn't say people are doomed and this is the sporadic form of the disease so it is affecting people in their eighth decade albeit if you are a homozygote for that genetic variant it does bring your age of onset a little bit closer we spend a lot of time thinking about how EpoE4 causes the disease unfortunately we still don't know but there are many theories that I could go into if someone is interested so 50% of people won't get it and similarly if you don't have EpoE4 even though your risk of getting Alzheimer's decreases you can still get the disease interesting and also with this new research around genetic testing and what we are learning about the genetic factors of Alzheimer's disease an anonymous attendee asked do you recommend elderly people or anyone really to have a test for that gene for example every few years or something how would that work clinically I think I have to be a little bit careful here giving clinical advice as I am a scientist but I think most people would recommend that if you have a very strong family history of the disease for example Alzheimer's disease you have a number of first degree relatives and then you probably should go and get some genetic testing or at least go to a genetic counsellor and that testing would be done on the genes including amyloid precursor protein gene APP and two others when it comes to EpoE4 and testing I know there was an Australian actor and found out that he had two copies of the EpoE4 I don't know at the moment if we could do anything with that information so I would advise people not to do that the variation on that theme is that there have been people put into trials who are EpoE4 homozygates so they have two copies for the amyloid modifying drugs so there are reasons why you might want to know but in general that information probably won't help you and may just lead you to having to worry one other thing I should say is genetics you have them for life so if you were to find out you were EpoE4 at 20 you would still be at 80 years of age so it's not something you would have to continue to do your genetics are permanent and mutable in just about every situation so definitely not having to go for a test after test okay and Viv asked in general with brain health what about general anesthetics because it seems that many people are concerned about how general anesthetics affect brain health there is something called well brain fog we use that term transient dementia that in certain elderly people when I make the point elderly say in the 70s at least 70s where they do develop a dementia it tends to be transient as far as I know but it is a known thing now what that mechanism would be I think we would all be guessing and I wouldn't hazard a guess at the moment I don't know enough about it I mean if you then compare that with the amount of general anesthetics that happen on a daily basis and I think the risk is minimal compared with that yes it is certainly something that does happen it often has a transient effect and people do recover their cognitive function but it is something that we are interested in but I will not know what the mechanism would be okay another question Steve asks what are the epigenetic factors that are relevant to dementias simple answer there is yes and just to clarify what Steve will be referring to this is the idea that there is some changes to your genetics that aren't heritable there are two types it doesn't really matter going into them but it appears that for cells like neurons they can accumulate over the life of the person these epigenetic changes which will affect gene expression patterns I talked about transcriptomics which is looking at gene expression but there are other experiments you can do where you can look for epigenetic changes and there is evidence that there are these changes associated with the disease it is not my forte but there is no doubt that they are important epigenetics it is a natural process it is a way that we can turn on genes at different times of our lifespan working out what is normal from what is abnormal is always a challenge but yes it is part of the puzzle okay great we have also got two questions here one from an anonymous attendee asking about COVID and possible links to dementia Angie asked specifically if there are any links between people who have had long COVID or significant long term brain fog as well thank you really for that question anything that is COVID related is sort of just come across our so to speak it seems like we talk about the direction of causation in these diseases and it seems the other way around that if you were a higher risk of people with dementia or a higher risk of COVID related mortality moving back in the direction when the COVID is bad for dementia I did read a paper the other day talking about the risk factor but not because the COVID virus or SARS-CoV-2 virus gets into the brain they actually think it is more from the respiratory point of view and relates to hypoxia so just not as much oxygen reaching the brain and contributing to dementia that way long term brain fog or long term brain fog with associated cognition deficits we just don't know enough about it at the moment but it is certainly worrying there has been there has been a mouse model where they had been deliberately infected with COVID-19 and they showed that they could increase the amount of ammo and that is certainly something we are looking at but as I say at the moment they do think that is a result of the hypoxia rather than the virus actually getting into the brain okay great and just really while we are right up to the hour if we can squeeze in one quick question from Rose asking how do people plan to risk do you have any advice or thoughts on that I think the only people that are really at risk and this is a very rare these are a very small part of the population and less than 1% of those actually carry a mutation even if you are homozygous for the two copies of FOE I said your lifetime risk is 50% you are going to affect you in your 80s so I would really say to young people or people up in the middle age and even into their 60s and 70s I would not be worrying about that other than that the best advice is that by remaining physically active not smoking and all of those advice including diet like the Mediterranean diet these are all going to reduce your chance of dementia because for the card carrying dementia sufferer they are going to have a component of Alzheimer's disease causing your cognitive decline but also a component of vascular dementia so reducing your chance of that is going to prolong your cognitive function there is these treatments on the horizon in Australia that have been approved in the United States I mean in some ways and disappointingly that we are talking in levels of 27% of reduction in cognitive decline over the period that the people were on the trial so they are not massive effects and that is probably what we are working on so our advice at the moment is the same advice for healthy body really not smoking, exercising and good food but other than that even if you did have these genetic variants that increase your risk of Alzheimer's disease I wouldn't be worrying too much about that okay great well thank you so much for your time Greg and thank you everyone for your questions sorry that we couldn't get to all of them we had a lot of fantastic questions tonight but yeah thank you so much and we hope everyone has a fantastic brain awareness week thanks for joining us