Transcript
[Beginning of recorded material]
[Title card: Dementia Australia]
[Title card: Chronic Traumatic Encephalopathy]
Dr Mobbs: Welcome, everyone. It's a delight to be speaking with you today on what has really been a buzz topic lately, this CTE, or Chronic Traumatic Encephalopathy, which is the long name. And this is a really important subtype of dementia that I'd like to help everybody here today learn about, and I have my details there if there are any further questions. My name is Dr. Rowena Mobbs, I'm a neurologist with the Australian CTE Biobank, and I work at Macquarie University, and it's an absolute pleasure to be with you. This is our team at Macquarie University working hard on CTE, a nd I'd certainly like to make the important acknowledgement of country, that we acknowledge the traditional custodians of the Macquarie University land, the Wallumattagal clan of the Dharug Nation, whose cultures and customs have nurtured and continue to nurture this land since the Dreamtime. We pay our respects to Elders past, present, and future.
I alluded to this being a buzz topic, and certainly, there has been a lot of headlines within the media, there has been a movie, as well, in terms of concussion and CTE. And we welcome this interest because, as always, in dementia, we can do more. There needs to be more care, more understanding, more research around these subtypes of dementia. And this is an important young onset dementia very often. Often asked early on, when I see people who may have CTE or are concerned about it, what actually happens when you have a concussion? What happens when the brain is shaken? And some talk about the brain as being a jelly-like substance or a butter like substance, so it's certainly a soft substance, certainly relative to the skull. And often, what can happen is the brain will shake against the skull, and there are different angles involved, different forces that may be relevant of both acceleration and deceleration.
There can be a bell ringing effect, and some studies would suggest this is really quite frequent, 50Hz in nature. And generally, we're talking about strong forces to associate with a concussion of 40gs or more, and concussion is really a disturbed function, not necessarily structural changes, although I will talk about some of the potential changes here, such as the axons, those connecting fibres of the brain or the highways of the brain, having sheer injury or damage. There can be swelling, as you would expect, like a bruise or an injury anywhere in the body. There can be white matter injury across those connecting fibres in the brain, we call that the white matter, the connections. And there can be excitotoxic changes – so these are types of special inflammation that can associate with cell death or loss of neurons after a head impact. We can see, in some studies, that there is potentially microscopic injury.
We don't yet have imaging that can show us that change. Rather, we suspect there are many microscopic injuries that could occur, and that these may be not seen on an MRI, but if you did look at the brain, if you happen to see that change, even after someone has passed away, you may see that there are changes, they are visible macroscopically even, in some cases. Most people, however, after these milder traumatic brain injuries, will recover well. Of course, it's a spectrum, and every brain is different, and every concussion is unique. As we all know, many of us can sustain a head injury from lots of different ways. So right from our early childhood through falls, for example, falls in sport, car accidents, falls when we're older. And importantly, through intimate partner violence or family violence, this can occur. And there has been a very important publication from Brain Injury Australia, in collaboration with the partners shown here, looking at the prevalence of acquired brain injury amongst victims and perpetrators of family violence. And this was Australia's first evidence-based study of brain injury associated with family violence, so I highlight this here for you.
So, what is a mild traumatic brain injury? Well, we say the term concussion. We presume that this results in microscopic injury at least, not visible on imaging or some sort of dysfunction. If there is actual injury microscopically, this is known as mild traumatic brain injury, or MTBI. Concussion means that there are symptoms after a head impact. And it's important to know that this may be direct, such as a direct force, such as a player hitting the hip of another player with their head, or it could be an indirect force, and so this could be a tackle, vibration, or whiplash effect, or a whiplash during a car accident, for example, where you still get that shaking of the brain, and you end up with a concussion.
Concussion may be delayed as far as the symptoms go, so even days, weeks or months after an injury, symptoms can emerge. And there are very much mixed results in the science as far as the rate of recovery. Most studies would suggest that patients recover within a fortnight, within two weeks, very often, but there is this concerning body of work now that suggests that 10 or 15% go onto the post-concussion syndrome with symptoms ongoing, up to 28% can be symptomatic at two years in some studies. And so, obviously, this needs more research and is of concern. It's a different spectrum of head injury to what we see in severe traumatic brain injury, where we can have very clear changes on imaging, such as this imaging which shows tractography, and changes that are very clearly visible in early and later, after a traumatic brain injury.
With concussion and mild traumatic brain injury, we are left with these sorts of screening tools such as the SCAT5, to try and assess a patient for their symptoms, and how they examine neurologically. And so, preferably, this is done by medical staff, and they can confirm that a patient has had a concussion. Importantly, there are the observable signs of concussion. So, lying motionless or loss of consciousness, for example, but a loss of consciousness or a knockout is only a minority of concussion. Most concussion is the symptoms or signs after the head impact without a loss of consciousness. So, you could be wobbly on your legs, this is called ataxia. You could be slow in your movements, or confused, and stunned, or slurry in your speech, for example.
I'd now like to talk on the concussion-related syndromes, looking at this spectrum of head injury right through to dementia. So post-concussion syndrome, it's an arbitrary diagnosis of symptoms at least three months and beyond after concussion. And the actual syndrome is recognised, but the correlation of a disease process within the brain is very unclear. Then, we have migraine that can occur, or headache syndromes after a concussion, and these symptoms can be identical to some you might see immediately after a concussion. Things like dizziness or unsteadiness, confusion, tinnitus or ringing in your ears, feeling fatigued, as well as the typical headache that you might suspect.
There is a rare syndrome called second impact syndrome, which is where there can be brain swelling if there are two concussions within a quick succession, and then there's CTE, that I'm going talk mainly about today. So, the incidents and prevalence is unknown of this condition. There is early data that needs to be confirmed. The majority of researchers in American football, both at amateur and professional level, there are changes of this condition affecting behaviour, personality, and cognition, and it is a progressive condition like all types of dementia.
The observational studies that we do have show that CTE in sports, but also non-sports related circumstances can occur, and I mentioned intimate partner violence, there's a lot of work in military-related trauma, and often, we think of blast trauma, occupational injuries, and falls. But I do want to emphasise that not everyone will go on to develop CTE, who is exposed to a certain amount of head injury. There are estimates that, perhaps, around four or 5% of the playing population in NFL may have CTE, but this research is very early, and it's simply unknown. The incidence is approximately 20% in professional boxers however. There is a larger body of work studying boxers for what used to be known as dementia pugilistica.
We do, however, have recent research out of the UK that suggests there is an increased rate of dementia overall in football or soccer players, in the order of three times risk of dying from dementia if you have that background. And very recently, only in the last few weeks, there has been release of data suggesting you have twice the rate of dementia if you have a background of rugby union, and that was a study in over 600 elite but, nonetheless, amateur and professional athletes. In that study, there was also an increased rate of Parkinson's disease in the order of three times the baseline risk, and motor neuron disease. This is, of course, a rare condition, but in this study, there was identified to have an increased relative risk of that in patients with CTE.
So, what is CTE as far as the clinical characteristics or the symptoms that one might have? CTE is a condition where there can be a loss of regulation of behaviour, so it may be easy to feel irritable and angry or become aggressive, and often, this can be due to a minimal trigger such as a road rage incident, or feeling angry if someone's in front of you in a queue, for example. There can be confusion, so a disorientation to your surroundings, or a loss of awareness and memory of time and events. And there can be confabulation, which is where there is an inaccurate content to one's language because of memory loss. There can be poor short-term memory overall. And often, we find in the research that this is the working memory, or the learning memory. So that's your memory on the run, day-to-day, that very immediate flexible learning memory that we have that helps us get by, rather than the short-term memory of what might have happened a week ago. And then the longer-term memory, although as the condition progresses, that can be affected too.
There is overall relative preservation of long-term memory, much like Alzheimer's disease initially. There can be poor decision making and a tendency of impulsivity. There can be depression and anxiety, very commonly and severely so, and some patients with CTE have had suicide as well. And there is little to no insight into many of these symptoms. Often, the report of the family or collateral history from others is needed. A poor self-awareness, and this is typically reflected in a frontal lobe disorder such as CTE, and other subtypes of dementia. And in some patients, only a minority, but in some, there is self-medicating behaviour often. So, there may be an alcohol use disorder, or other substance use disorders, in response to trying to regulate these symptoms.
Just to remind all of us that dementia is the umbrella term, it's the term for a gradual loss of neuronal tissue and brain function over time, and there are many subtypes of dementia. These are thought to be largely protein, and other abnormalities within the brain, and a loss of brain volume overall, we call this atrophy. With this, there is a loss of function over time, although the changes that we see under the microscope do not always correlate exactly to what we would predict as far as symptoms go. The picture I've included here is of Bondi Beach, around 1900. And I use this to highlight that, dementia really is a condition of our times now, as opposed to these children who would've had a much lower life expectancy of around 50 years, and faced famine, and infection, and war as causes of mortality. But now, we have the wave of dementia, and we really need to get along, and do all of this good work, and research, and care to help everyone.
In terms of types of dementia, well, the type and the duration vary widely of course. So, Alzheimer's disease, you can have a progression very typically of six to 10 years but there are exceptions, of course. In frontotemporal dementia, the rate of change can be very variable, but it is over years. Lewy body dementia, again, is very variable, typically two to eight years. In CJD, or Creutzfeldt-Jakob disease, this is a shorter and faster type of dementia, typically months rather than years. Parkinson's disease can have associated-type Parkinson's dementia, but this is a longer duration into the illness, 10 to 20 years into the Parkinson's disease. And then there is alcohol related dementia, for example, which is highly variable, again, over years typically. But CTE is, compared to these types of dementia, relatively slower, so we think there is a 10-to-25-year progression, typically, so although it's a subtype of dementia, it seems to be very slow, and therefore, perhaps it has been missed, perhaps it's harder to detect and diagnose someone with CTE if the changes are very gradual, and over such a long period.
The role of the neurologist – so what I do day-to-day in the clinic – is really to assess for the changes of CTE, but also to exclude other causes, and what does make life complicated is that the types of dementia I've mentioned can overlap. But we do studies like this, the top colourful images are from what's called a PET scan, so that's a metabolic picture of the brain. I'm really looking at if any areas of the brain are running on empty, as far as their metabolism. The bottom pictures are the MRI of the brain which shows us the structure, and can show us any volume loss of the brain, but also, any bright, white changes that might reflect a vascular change. And unfortunately, for CTE diagnosis and detection, we don't have the liberty of scans that really show us CTE changes distinctly. We are yet to see that science, and CTE is really a confirmed diagnosis after life. Now, I want to reflect that CTE is really the accumulation of head injury. We're not talking about isolated one or two hits to the head. It's very often hundreds if not thousands of hits to the head. We distinguish between concussion, which is the head impact leading to symptoms, and sub-concussion, or sub-concussive burden. So, these are all the littler knocks, potentially littler knocks, that do not have symptoms associated with them, but could still cause brain damage. We see that there are high risk individuals who may have played at least a decade of contact/collision sport, or other contact environment, and then the lower risk individuals. We need to identify tests that can help us determine who is high risk and who is low risk, so that we can target future treatments and research to that group. CTE is the accumulation of these impacts. It's an irreversible condition, it's progressive, being a type of dementia, and it forms the neurocognitive disorder criteria under DSM, as a type of dementia.
In American football, the data has extended to recent studies that perhaps show an 84% rate of CTE in professional football players. So, they had one study here, 223 out of the 266 participants had CTE found after life. And they showed that there was a correlation between the amount of head injury you had and your risk of CTE – so for every 2.6 years you played American football, your risk of CTE roughly doubled. So approximately 30% annually going up, as far as odds-risk ratio. And the players with CTE were 10 times as likely to have played longer than 14 and a half years, and if you played before age 12, this typically led to an earlier cognitive and behavioural decline of around 13 years earlier presentation. The youngest person with CTE known in science was age 25.
Who gets CTE? Well, these are the sports listed here. I've highlighted in pink that there is rugby union, rugby league, and Australian rules football confirmed in Australian research as far as CTE. There is suspicion that in equestrian, for example, jockeys, there can be a rate of CTE. There is work looking at defence, mining, manual labour, falls, domestic violence I've mentioned, and also, headbanging behaviour in some individuals.
What are the pathological changes of CTE? Well, I mentioned it's a postmortem diagnosis using histochemical staining, looking for something called hyperphosphorylated tau, the tau protein, which we use special techniques for. This pattern of tau deposition distinguishes CTE from other common types of dementia, even though tau can be a factor in other types, this is in a particular pattern, and it may be its own particular subtype of tau. And CTE was originally identified by Martland, the neuropathologist in 1928, in boxers. And for many years, it was thought that it was purely a condition affecting boxers. But then in 2005, there was work extending to the American footballers. By that time, there were only 42 cases of CTE in the medical literature, but this is vastly different now. And tau is found in this distinctive pattern in the brain, it's in fact a normal cellular protein, but in CTE the tau goes awry, and there are abnormal forms of this.
We see tau in other conditions I mentioned, so Alzheimer's disease, but this is along with beta-amyloid. We see it in corticobasal degeneration, progressive supranuclear palsy, and other conditions. And here is an example of some of the tau deposition that one might see in CTE. What we see is that the tau pattern, the staining, can be in those valleys and clefts of the brain – what we call the subsocial region of the brain, where the folds go down across the brain. That's very interesting and intriguing, we don't see that in other types of dementia, and perhaps, there is a mechanical or movement vulnerability to those areas, perhaps there is a tendency of inflammation of the cells in that area for whatever reason that might be, and so, that's a real interest.
We then see, again, like other types of dementia, spreading of this protein to different areas of the brain. So, it might go from those valleys of the brain down to more general changes within the brain tissue. Often, we see changes around blood vessels in CTE, and it can extend to those memory areas, the temporal lobes, which are shown here in stage three CTE. At that time, you start to get a loss of brain volume in those areas. In stage four, there is a more extensive CTE tau deposition scene, and by that time, there are more extensive troubles, that a patient faces more global symptoms we would say.
Here is a picture of some brain slices – we have a normal brain, but you can see in the brains below that, the brain with CTE, that there is a larger area of those fluid-filled cavities, the ventricles, and they're highlighted here. And there is also a loss of brain volume overall, and this would be a lighter brain if you weighed it, so these are the sorts of changes we see. And what we need to do is identify it in life earlier, so that we can research the condition and develop ways to manage it and treat it.
We try to detect for a thing called traumatic encephalopathy syndrome, TES. So, these are the clinical features that you see in life that we think are equivalent to CTE that's found neuro pathologically. There are international criteria in research for diagnosing TES or CTE. We have patients who are categorised into possible CTE and probable CTE. We use a combination of criteria as follows, so looking at the history of significant, repetitive brain trauma, and this is often distant, so they may be a retired player, and then develop CTE down the track. The patient has a degree of neurocognitive impairment, so we demonstrate, neuropsychologically, that they have changes of their thinking that is abnormal compared to their baseline. The neurocognitive impairment cannot be explained by other neurogenerative diseases, the role of the neurologist or other medical causes.
Of course, we do think about mimics of dementia, so things like migraine that can cloud you after having head injury. We also look for things like sleep apnoea, where your oxygen levels might be low overnight, and that can lead to memory loss during the day. Depression can mimic dementia, so simply feeling very depressed and low can associate with memory loss and a presentation like dementia. So, we look for those things, and we treat those conditions, and then we see how the patient is on testing. And we measure the degree to which the patient is suffering from the neurocognitive impairment – so how impaired are they? What types of trouble with function are they experiencing?
There are no in-life biomarkers, as I mentioned, that can provide this diagnosis, it's only confirmed after life. But we do perform imaging, we try to exclude any- in concussion, for example, many patients might have had a CTE, excluding bleeding or big trauma fractures, that sort of thing, but in CTE, of course, this can be normal. MRIs still remain poorly sensitive and specific for CTE, particularly in the early phase, but if a patient had advanced CTE, you might see some changes or advancing CTE. So, there are changes such as a thing called a cavum septum pellucidum that we look for on imaging. We're looking at the volume of the brain in different areas according to statistical evidence for age changes, so this is called volumetric studies. We're also very interested in something called connectomics, so looking at the connections of the brain that we can translate into colours and imaging, and say this area looks abnormal or not, and that's very much in the research realm at this stage.
And there are studies worldwide looking at PET scans. They're the metabolic scans I mentioned, looking at a particular type of tau that might show up and show CTE, rather than other types of dementia. I mentioned a person called a neuropsychologist, so they're very important to the diagnosis of probable CTE. They can confirm that there is a particular pattern of cognitive impairment on testing for that patient's baseline, and this is really important, but can take around two to three hours to do, it provides an extensive report as to other factors to that patient's cognition, and simply being able to understand which areas of thinking are affected can mean that we can target those areas for therapy. So, we might work with the neuropsychologist or another psychologist around ways to manage mood, for example, or help lay down memories better, or change the environment in which a patient lives to try and improve their cognition, along with medication.
As far as therapies go in the neurology clinic and other cognitive clinics, we look towards mood improvement – so antidepressants, there are many modern antidepressants that can have few side effects. And clinical psychology for cognitive behavioural therapy, for example. It's really important for those with CTE to stay social, physical, and intellectually active as well. And you can often combine the three in different ways. It's important to have a routine and establish really good patterns of eating well so that you can ward off any frailty and maintaining self-care. And the principles of good self-care, maintaining social, physical, and intellectual activity, and avoidance of toxins like smoking and heavy alcohol, that will hold a person in good stead for, hopefully, preventing any vascular component to a dementia, or triggering other types of dementia in different ways. And we hope that we can reduce the rate of dementia in Australia by good management of these sorts of modifiable risk factors for someone, so we encourage all of our patients to think on this.
We can try and stabilise that mood. I mentioned the anger and rage attacks that a patient might have, so this is sometimes through medication, often, through environmental support. And we do run a program of group therapy, for example, to support patients and their families with probable CTE but we might also remove distractions, and try and control the environment is clear and contrasted, and really use those environmental measures with an occupational therapist advising, for example. And we do provide memory medication directly, and Donepezil is the one that is often used in Australia.
The research is very exciting, and I mentioned connectomics, looking at patents of connection change, or special MRIs and PET scans for the future, and so, I thought I provide some examples. The future in CTE will really be about better recognition, earlier detection of this subtype of dementia, and simply thinking about it. When I began my medical career, I certainly wasn't very good at asking about a concussion and sub-concussion history, but I think it is important for doctors now to start to be aware of this, and for patients and families to think on their own cumulated history of head injury and think, “when did I play? How long did I play for? Or how long was I exposed to head injury for? And how many concussions I might have had, which are symptoms after a head knock? And what my accumulative burden is? what is my risk?” And going to talk to your doctor, I think, is really a good idea if you're worried.
We can look at prevention strategies in sport, and also, in non-sporting related head injury. We can hunt for those biomarkers, so developing research in blood testing, testing the brain fluid, the cerebral spinal fluid or CSF, and using special imaging to detect CTE. We hope to help develop clinical guidelines for CTE, both for the detection and management, and research eventually will be targeted to disease modifying agents and cures hopefully, one day. And we're starting to see the cuff of that research come through in conditions such as Alzheimer's disease.
here can I get help? Of course, Dementia Australia run fantastic services for support across the country. I will mention, of course, Brain Injury Australia who are also very helpful. The Concussion Legacy Foundation have expertise in CTE in America, and there is an Australian arm now. And certainly, always do go and talk to your doctor, consider seeing a neurologist or other cognitive specialist if you're worried about CTE, so that they can look into it more for you. And with that, I will close, and thank you very much for your attention.
[Title card: Together we can reshape the impact of dementia]
[Title card: Dementia Australia. 1800 100 500. Dementia.org.au]
[END of recorded material]
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