Are you smiling or frowning?

The inability to understand facial expressions can have a profound effect on the lives of people with dementia and their families, says Dr Fiona Kumfor.

Recently I met a lady who, despite only being in her 50s, was suspected of having dementia. Susan* and her family had come to the dementia clinic at NeuRA (where I conduct research) to get help with a diagnosis.

Susan wasn’t forgetting things; in this sense, her mind was very sharp. But in the last year she had become far less socially engaged and caring, even towards her teenage children. For example, she had started telling private things about her children to people outside the family; she didn’t seem to recognise that it was embarrassing for her children. This was very distressing for her family, even though Susan herself felt that nothing was wrong.

Dr Fiona Kumfor studies how dementia can disrupt a person’s ability to understand emotions.

While this may not sound like the dementia you’re familiar with, the effects of this disease are in fact much broader than the confusion and memory problems of Alzheimer’s disease. People with the type of dementia we saw in Susan, called frontotemporal dementia, show profound changes in their behaviour and personality. One of the most difficult changes that families must cope with is a loss of empathy that occurs, at least in part, because of an inability to interpret facial expressions.

Understanding what a frown means

For a healthy adult, interpreting facial expressions happens automatically and rapidly. Our research focuses on how this complex skill is affected in patients with frontotemporal dementia. Our research has revealed that people with this disease are unable to distinguish between facial expressions very well at all. Because they might mistake a sad expression for an angry one, they also have difficulty understanding how other people are feeling and responding appropriately.

So what happens in the brain to cause this change? Importantly, our study has revealed for the first time that shrinkage in the frontal and temporal parts of the brain, in regions called the amygdala and insula in particular, is responsible for this loss of emotional understanding. Previous studies have shown that these regions activate in healthy people when they view emotional faces.

The image on the left is an MRI scan of a person with frontotemporal dementia. The black areas show the frontal regions of the brain that have shrunk due to dementia. The scan on the right shows a healthy adult of the same age.

This loss of emotional understanding undoubtedly makes interacting with others challenging; people with frontotemporal dementia are no longer able to understand the subtle social cues that healthy people take for granted. It can cause conflict if they misinterpret their friends and family’s emotional expressions. This was certainly the case for Susan; her family told us that she didn’t seem to understand when they were feeling upset or frustrated anymore.

Improving quality of life

Unfortunately at present no cure exists for frontotemporal dementia. We do hope, however, that our findings will help in the development of techniques to improve the quality of life for people with this disease and their families.

In fact, we’ve already had some heartening results. A second study we conducted showed that, in some cases, exaggerating the emotional expression improved how well patients recognised the emotion. For me, this finding is particularly encouraging because it suggests that even simple techniques may have a direct and positive impact on how people with frontotemporal dementia and their families can continue to communicate and connect.

*name changed

The sensitive topic of brain donation

Brain donor program coordinator Lauren Bartley says while it can be difficult to talk to people about brain donation, it’s for a very important cause.

When I first began recruiting to the brain donor program at NeuRA and the Sydney Brain Bank, I found it difficult to broach such a sensitive topic with the participant and their family members. After all, how do you ask someone you have met just briefly if you can have access to their brain tissue after they pass away?

This is a discussion I’ve had to have with all our research participants – and one that I no longer shy away from. I know that every brain is valuable and have seen firsthand that every donation brings us closer to understanding more about dementia.

Sometimes there can be confusion over whether the tissue we collect will be transplanted into another human (which it’s not); other times, I’ve found that participants think their brains won’t be useful because of their cognitive impairments.

Lauren Bartley is a brain donor program coordinator at NeuRA.

It’s actually brain tissue from people with these very impairments that is helping scientists at NeuRA understand why proteins that cause dementia begin to deposit in some people’s brains and not others, and how this occurs.

In some cases, it’s difficult for a neurologist to determine if the patient is suffering from early onset Alzheimer’s disease (AD) or frontotemporal dementia (FTD). While clinically these dementia syndromes can appear similar, the brain tissue pathology is quite different. Looking at brain tissue has been essential for understanding the differences in pathology between AD and FTD.

Thanks to people who have donated their brain tissue in the past, we now know that the brain tissue of people with Alzheimer’s disease is marked with plaques formed by the beta-amyloid protein and tangled accumulations of the tau protein.

The tau protein also accumulates in frontotemporal dementia, depositing not in tangles but as inclusions inside brain cells called Pick bodies (FTD is also known as Pick’s disease). Some people with FTD also have pathological inclusions of other proteins such as TDP-43 or FUS.

“This is at the heart of what’s driving our research: we need to come up with new ways of accurately diagnosing dementia while a person is still living.”

Because of the heterogeneity of pathology in FTD, it’s impossible to predict which protein is responsible for the illness with the clinical tools we currently have at our disposal.

I can recall many times when participants were only found to have evidence of motor neurone disease (in addition to their dementia) during the autopsy process. There have been instances where we found participants who had been diagnosed with FTD actually had Alzheimer’s disease pathology and vice versa.

If we had known the true cause of their illness during life, they may have been able to access therapies or medicine to reduce the impact of their symptoms. This will become increasingly important as new therapies for dementia syndromes become available.

This is at the heart of what’s driving our research: we need to come up with new ways of accurately diagnosing dementia while a person is still living.

Helping us improve diagnosis during life is one of the reasons why brain donation is invaluable, and it’s why I’d like to thank each and every brain donor who I’ve had the privilege of working with at NeuRA.

 

More information about brain donation

While I am not able to accept brain donations from the general public, we do accept brain donations for AD and FTD research from people who have participated in research at our clinic. There are also circumstances where people who we have not seen in our clinic but have had a diagnosis from a neurologist/geriatrician and previous brain imaging (preferably MRI) can also be enrolled.

After the Sydney Brain Bank at NeuRA has finalised the report identifying the protein that caused the dementia, I send this report to the families and clinicians. The tissue donation is then used in ethically approved projects performed by medical researchers across Australia and the world.

If you are interested in finding out more about brain donation for medical research into AD and FTD, please contact me at frontierbiomarkers@neura.edu.au

“Help me, I’m terrified of falling!”

Being afraid of falling is very common – and not something you should have to live with, says NeuRA researcher Joanne Lo.

Last week I went to visit an eighty-year-old woman who was terrified of having a fall and ending up in a nursing home. ‘Florence’ loves her sunny unit and enjoys the independence of living in her own place and, until recently, was a very active and confident woman.

Earlier this year, however, she had a particularly bad fall on the stairs to her apartment block. She now lives with a fear that weighs on her every day. Her fear of falling is so overpowering that she avoids any activity that might be the least bit risky, such as walking the short distance to her local shops.

Meeting people like Florence reminds me how far we’ve come in the last decade in terms of what we can offer to older people at risk of falling. Not so long ago, if you were elderly and fearful like Florence, you might not have dared to venture outside and possibly become more frail, depressed and socially isolated.

NeuRA researcher Joanne Lo is part of the falls and balance research group.

But as a result of research from around the world – in which NeuRA’s Prof Stephen Lord and his team have played an important and active role – we have gotten better at helping people fall less. At the heart of these improvements is a simple battery of tests developed at NeuRA, known as FallScreen.

We use FallScreen to test a person’s physical function; for example, we measure how much a person’s body sways while they attempt to stand still on a foam mat. We use the results to predict a person’s risk of having a fall in the next year.

In the postural sway test, the patient attempts to stand as still as possible while we measure how much their body sways.

We know what to test for because, early in his research career here at NeuRA, Prof Lord assessed hundreds of older adult volunteers to see what was different about those who fell during the subsequent year. He identified five primary areas of physical function that contributed to an individual’s risk of falling: their vision, the speed of their reactions, leg sensation, muscle strength and balance. He then devised simple methods of assessing these different areas and the assessment tool known as FallScreen was born.

Studies have found that FallScreen allows us to predict future fallers with an accuracy of 75%. Why is this important? Because if you know you’re at risk, then you can do something about it.

In Florence’s case, I assessed her as being at moderate risk of falling in the next year. She was surprised; in her fearful state, she had felt she was at very high risk. I was able to show her specific exercises to strengthen her leg muscles and talked about ways of addressing her fear so that she could continue to exercise confidently.

The FallScreen assessment tool is now being used in hospitals and clinics around the world. This means that health practitioners have a scientifically-validated way of testing where the potential deficits are in their patient’s physical function and are better able to target these areas in their treatment. This is good news for maintaining the patient’s independence and helping them to prevent a fall in the future.

If you think you are at risk of falling, or have a fear of falling, I can’t urge you strongly enough ask your GP for a referral to a falls clinic for an assessment. There are many things you can do to reduce your risk; being assessed is just the beginning.

For example, at NeuRA we are currently looking into ways of improving exercise programs, such as using an iPad app as a digital personal trainer. This is just one of many ways we are trying to reduce falls in older people. If you’d like to find out more, please visit our website.

“My memory isn’t what it used to be. Am I developing dementia?”

PhD candidate Marshall Dalton explains that there’s a big difference between memory lapses due to healthy ageing and the memory problems associated with dementia.

I conduct research into the effects of healthy ageing and different types of dementia on memory processing. Over the past few years, while giving community talks about memory and dementia to Rotary clubs across Sydney, it’s been common to find people worrying about their own lapses in memory. I’m frequently asked questions along the lines of, “I know that my memory isn’t what it used to be. I misplace and lose things around the house more often than I used to. Could that mean that I am developing dementia?”

It’s important to understand that not all memory problems are indicative of dementia. Memory problems can be caused by a number of biological factors. Prolonged periods of stress or anxiety, depression, infections or thyroid imbalance can all result in impairments in memory. Some medications have side effects which affect memory and even simple things such as poor nutrition and dehydration can cause memory problems and are easily overlooked.

Marshall Dalton is a dementia researcher at NeuRA

Marshall Dalton is a dementia researcher at NeuRA

Some memory problems, however, are simply a normal part of ageing. Memory lapses happen to us all, young and old, but as we get older the frequency of these memory lapses can increase.

Common examples of healthy age-related memory problems include an increased frequency in misplacing items (such as keys), problems remembering appointments or remembering where you parked the car. We may also become slower at retrieving information from memory but, importantly, with a bit of time or some prompting, the information is still there.

The more insidious memory problems experienced by people with certain types of dementia are very different to those seen in healthy ageing. People with dementia may forget what certain items are or what they are used for and may also forget the names of loved ones. They may become unable to learn new things such as how to operate a new microwave or how to get to the new supermarket that has opened around the corner.

But why does memory go wrong? A region of the brain called the medial temporal lobe (MTL) contains a number of structures that are crucial for memory processing. Our memory depends upon healthy communication between brain cells in this region and brain cells in other parts of the brain. Brain cells communicate with each other through special connections called synapses. As we age, the number of synapses decreases. As a result, communication between brain cells becomes less efficient.

“Age-related memory problems are the result of reduced efficiency in communication between brain cells, whereas memory problems in dementia are the result of cell death.”

In contrast, disease processes in some types of dementia result in the death of brain cells in the MTL. This results in the loss of communication between cells, which causes the more serious memory problems seen in dementia. Simply put, age-related memory problems are the result of reduced efficiency in communication between brain cells, whereas memory problems in dementia are the result of cell death and the gradual loss of cellular communication.

In closing, although it’s important to understand that memory problems can result from a number of possible causes, including healthy ageing, it’s important to stress that memory is very complex. If you notice a significant change in memory problems in either yourself or a loved one, it’s important to get advice from a medical practitioner.

 

Restraining children in cars: moving in the right direction

NeuRA’s Dr Julie Brown has looked at the impact of the 2010 NSW child restraint legislation – and has good news.

I am so happy that we finally have some good news to share with parents, carers and those advocating for change to reduce child injury – it seems there have been positive changes in the way children are travelling in cars since the introduction of new laws requiring appropriate restraints for children up to at least age seven.

Australian parents have always been really good at getting their children into restraints. The old ‘What about me?’ and ‘Click Clack Front and Back’ media campaigns that were everywhere in NSW a few decades ago really seem to have got the message through. By the late 1990’s we had one of the highest rates of restraint use anywhere in the world, with more than 98% of children using a restraint whenever they travelled in a car. While this high restraint use worked to reduce rates of injury in children in car crashes significantly through the 80’s and 90’s, in 2003 we were still seeing alarming numbers of children killed and injured in crashes – despite the use of restraints.

NeuRA’s Dr Julie Brown (right) and PhD student Lauren Meredith (left) with their crash lab research equipment.

My colleague Lynne Bilston and I began studying in detail crashes where restrained children had been injured and we soon realised that most of the serious injury was happening when children were using restraints designed for older children and adults, or were not using their restraints in the right way. We then went out and looked at what people who weren’t in crashes were doing – observing and surveying more than 500 children across the state. And we found we had a big problem. Only about a quarter of the children we saw were what we would call optimally restrained. That is, they were in the right sort of restraint for their age (appropriately restrained) and using the restraint in the right way (correctly restrained).

If we just looked at the type of restraints they were in, we saw that about half of all children were in the right sort of restraint for their age (appropriately restrained). And if we looked at how they were using the restraint (ignoring whether they were appropriately restrained), we saw that about half were using the restraint in the right way (correctly restrained).

We also did a lot of other research to try and understand the barriers parents were facing in getting their child restraint practices right. I was struck by the fact that although parents really wanted to keep their children safe, especially in cars, there was just so much confusion out there about how best to do this. I think the new legislation and accompanying media campaigns helped reduce this confusion because they spelled out exactly what sort of restraint a child should use depending on the child’s age.

“This is really good news… we will now have less serious injury among children in crashes.”

Working with our colleagues at the George Institute for Global Health, we had the opportunity to go back out in the field and observe children in cars across western Sydney about 3 months after the introduction of the legislation. We were really excited to see that among preschool aged children, appropriate restraint use had increase by 20%, and that in our post legislation sample, children were more than twice as likely to have been in an appropriate restraint than the children in our pre-legislation sample. This is really good news because this sort of increase in appropriate restraint use will likely mean that we will now have less serious injury among children in crashes.

There is obviously still more work to do – to get appropriate restraint use up as high as possible, and also to revisit the design of child restraint systems to make them easier to use correctly. Having said that, these latest results are encouraging, and tell us we are moving in the right direction.

For information about our research into keeping children safe in cars visit us here.

Books For Brains

The NeuRA Foundation is looking to raise funds to support brain research via ‘Books for Brains’, which kicks off in October.

Sometimes an idea just ‘feels right’, and so it was when we conceived the idea for NeuRA’s Books for Brains event.

From the outset, it was clear to us that people who enjoy reading intuitively know that reading is good for their brains. And so the idea that people in book clubs would take a lively interest in the frontiers of knowledge about the brain, and how it works, was not a stretch.

Books for Brains is a NeuRA initiative calling on book clubs around Australia to put their heads together in the month of October and read a book with a focus on the brain and mind.

NeuRA’s Judy Dixon

The concept has received praise from a number of bestselling authors.

Norman Doidge, author of this year’s featured book, The Brain that Changes Itself, says:

“At this moment, while Australian neuroscience researchers are ‘punching well above their weight’ and making huge breakthroughs, so many Australians display an open-minded wonder about the brain. That’s why NeuRA’s initiative, Books for Brains, is such a wonderful idea. What could be more enlivening than digesting the meaning of new findings, which can so illuminate our lives, by getting together and discussing them within your book club – with the helpful, up-to-date comments on offer through Books for Brains from leading Australian researchers at NeuRA.

Ruby Wax, comedian and author of 2013’s bestseller, Sane New World, a story about what is it like to live with depression, says:

“The problem is in us; in our brains. The conflict is within ourselves. It’s those voices battering us and we project it out on the world. Inside our heads there is always war. I totally support NeuRA’s Books for Brains – unless we learn what’s in our heads, we will never resolve our own issues and the world’s.”

Peter FitzSimons, much-loved Australian author and social commentator, says:

 ”Books for Brains is a wonderful initiative to raise awareness about an issue growing in importance with every passing year. Once, while playing rugby in France, I was so badly eye-gouged I actually saw my own brain, and was satisfied it was big. But as time has gone on, I have become aware that none of us can take brain health for granted, and I fully support all efforts to make Australians aware of that very fact.”

Through NeuRA’s Books for Brains, we hope to encourage your book club to think about the importance of brain research. We want to encourage you to discuss one of our suggested books and hope that you find it stimulating, uplifting, funny or even moving.

To register and access this year’s book list, visit us here.

Can pain change our brain ‘maps’?

NeuRA researcher Flavia Di Pietro is investigating the maps in our brain and the role they might play in the pain experience.

There is a region of the cortex – the outer layer of your brain – that contains a precise and organised map of your entire body. Here, every part of your body surface is represented by a network or ‘column’ of neurons that is activated when that body part is touched or stimulated in some way.

This region, known popularly as the sensory homunculus and to scientists as the primary somatosensory cortex (S1), is a key site of research in the chronic pain disorder known as Complex Regional Pain Syndrome. CRPS is the focus of my research at NeuRA.

Flavia di Pietro is investigating the brain’s role in chronic pain – specifically Complex Regional Pain Syndrome

Complex regional pain syndrome (CRPS) is a disorder, usually of the hand or wrist, characterised by ongoing pain and dysfunction across several body systems. We don’t know what causes CRPS but the most common predisposing injury is a wrist fracture. Some of the signs and symptoms are altered sensitivity, muscle weakness, and changes in hair and nail growth. Intriguingly, patients with CRPS can also have altered perceptions of their affected limb, for instance they often neglect it (that is, they feel it is no longer theirs) or sometimes they perceive it to be bigger than it is in reality.

Using many different neuroimaging technologies, researchers around the world are currently investigating the brain’s role in CRPS. S1 is one of the regions most talked about, given what we know about its role in body representation and perception. Studies have investigated the function of S1 – or more specifically, the representation of the CRPS-affected hand in S1 – by stimulating the painful hand (e.g. with light touch or electrical stimulation) and then looking at the S1 activation that results, i.e. the coloured ‘blob’ on the brain scan.

Past studies have demonstrated that the S1 area representing the painful part re-organises; in fact the ‘blob’ has been shown to shrink in size. These findings are compelling given the interesting perceptual problems that a lot of CRPS patients have. These findings have contributed to innovative and non-invasive therapies for CRPS.

“Intriguingly, patients with CRPS can have altered perceptions of their affected limb.”

That S1 reorganises with pain, and the S1 representation of the CRPS-affected hand is smaller, is widely assumed and accepted. We wanted to know the true state of the evidence; had all the studies come to the same conclusion? We embarked on a systematic review. This involves trawling through the literature to find all the studies that have addressed this question of S1 function in CRPS, pooling their findings and also assessing these studies for their quality. In research this is a great way to get a definitive answer to a specific question.

What did we find? We found consistent evidence that the representation of the CRPS-affected hand in S1 is smaller than that of the unaffected hand, and that of healthy pain-free controls. But the evidence isn’t as strong we thought it would be: we were surprised to find so few studies, recruiting a low total number of subjects, and also a high risk of bias in their findings (namely in the ways they did their statistical analyses and reported their findings).

Our review is important because now we know what’s been investigated and what still needs to be done. We’re not sure what the shrunken hand representation in S1 might mean. We’re not sure if it causes pain or the other way around, or neither of these. But in light of the clinical integration of new therapies that theoretically target this reorganisation in the brain, it’s important that we better understand the brain’s role in CRPS. Here at NeuRA we are currently doing our own investigation into S1 function in CRPS, and the methods we are using have been informed by the findings of our systematic review.

Lost and forgotten: improving our diagnosis of dementia

Accurately diagnosing conditions of the brain such as dementia can be very challenging; there are no easy blood tests or scans that tell us without a doubt what a patient is suffering from. Diagnosis involves observing the patient’s symptoms and performing a number of clinical tests such as testing memory function, and depends on a good understanding of what symptoms differentiate it from other similar diseases.

Sicong Tu uses magnetic resonance imaging to detect tissue loss in the brains of people with dementia.

Alzheimer’s disease is the most common form of dementia. While most people are familiar with the name if not the symptoms associated with the disease, there is a common misconception that the memory problems seen in the early stages of Alzheimer’s disease are exclusive to this type of dementia. As mentioned in a previous post, however, there is increasing evidence to suggest memory is also affected in the early stages of a different form of dementia called frontotemporal dementia. Since memory impairment is not exclusive to one disease, this poses a problem for the diagnosis of dementia conditions.

The clinical research group at NeuRA that I work with, called FRONTIER, is trying to solve this problem. FRONTIER is an internationally recognised research program investigating younger onset dementias (under 65 years of age). FRONTIER applies a multidisciplinary approach combining clinical, behavioural and cognitive investigations to better understand the symptoms, behaviours and brain pathology that characterise different types of dementia. For those of you who have encountered Alzheimer’s disease, it is clear that while deterioration in memory is present, it is also accompanied by many other changes such as disorientation and confusion about time and place. In some cases, where the disease has progressed to a moderate severity, they may show a different perception of time such as preparing to depart after just arriving at an appointment or even becoming lost within their own home.

In a recent study by our group, we conducted an in depth examination of clinical memory and orientation performance in Alzheimer’s disease and frontotemporal dementia. We found that memory is indeed impaired in both Alzheimer’s disease and frontotemporal dementia, reconfirming that of an earlier study. Interestingly, however, orientation was intact in frontotemporal dementia patients but impaired in Alzheimer’s disease patients.

We also looked at the brain structures underlying memory and orientation using magnetic resonance imaging (MRI). We found that memory performance could be attributed to brain tissue loss in the anterior (front) regions of the hippocampus in both Alzheimer’s disease and frontotemporal dementia. Excitingly, we identified loss of brain tissue responsible for impaired orientation in the posterior (rear) region of the hippocampus, specific to Alzheimer’s disease. While there is a long history of research implicating the hippocampus in memory, it is becoming increasingly clear that different areas along the structure are responsible for different mental processes.

The scan on the right highlights the region of the hippocampus responsible for memory; the scan on the left highlights the region responsible for orientation. Tissue loss is this area is unique to Alzheimer’s disease.

Our findings have important clinical implications, namely that clinicians should consider measures of orientation in combination with memory to help distinguish Alzheimer’s disease from other dementia conditions. Our next step will be to develop novel assessments that can provide a more in-depth assessment of orientation. In this vein, we are currently piloting a new computer-based task that will hopefully allow clinicians to perform a quick and reliable assessment of orientation. Watch this space!

Brain Injury Awareness Week

This week is Brain Injury Awareness Week. More than 500,000 Australians have an acquired brain injury, so what can we do reduce the numbers? In this blog post, NeuRA’s Professor Lynne Bilston explains that prevention is key in cutting the numbers of those affected each year.

Lynne Bilston

Traumatic brain injury occurs when an impact to the head causes damage to the brain tissue. It’s very common – about 2500 serious brain injuries occur each year in Australia, and many more that are less serious. Even apparently minor injuries often have ongoing effects on people’s lives, and repeated minor trauma can predispose people to dementia later in life. Brain injury has enormous social and financial costs, profoundly affecting the lives of not only those with the brain injury but also their families. The lifetime cost of looking after people who acquire a brain injury in Australia in a typical year is estimated to be approximately $8.6 billion[i], much of that cost falls on individuals and families, not just on our health system.

So what can we do?

Improvements in emergency care after trauma have helped more people survive, but there are no drug treatments that make significant differences in function once a traumatic brain injury happens. Rehabilitation is a long and arduous road, with often only small improvements resulting.

Prevention of traumatic brain injury is therefore paramount.

To prevent brain injuries, we must understand how they happen and from there,  design effective prevention strategies, whether these are engineering design solutions such as improvements to car safety features and restraints, public education programs, or clearer regulations. These methods all help.

Research done together with my colleague Dr Julie Brown into injuries in car crashes – the leading cause of brain injury, details how these injuries are sustained in crashes, and what  factors contribute to brain injury. In children, we have shown that the most serious injuries can be prevented entirely if children are correctly strapped into the right type of child restraint for their size. This apparently simple approach works because the right restraint used properly stops the child’s head from hitting hard objects in a crash. If there’s no head impact, then the head can come to a stop relatively slowly. This minimises the acceleration forces on the head and prevents the brain from ‘sloshing around’ inside the skull, which in turn, dramatically reduces the risk of serious head injury.

Our research has led to new national child restraint laws, which require children to use the right type of car seat for their age. But our research shows that the laws alone are not enough. We must also help parents use the restraints correctly, otherwise they won’t work properly.

We have shown that better restraint labels make it easier for parents to choose the right restraint for their child’s size. Getting restraints checked by a professional can also reduce mistakes in how they are used. We’ve shown that education programs in preschools can help kids understand how to use restraints correctly.

The fact is, preventing brain injury is not only possible but vital, and needs the ongoing cooperation of neuroscientists, engineers, public health experts, teachers, and governments.