The Social Brain

Dr Muireann Irish uncovers the part of the brain that underpins social cognitive deficits in semantic dementia, further unraveling mysteries behind the disease.

It may sound like the subject matter of a science fiction movie, but mind-reading is a process in which we regularly engage. On a daily basis, whenever we interact in social scenarios, we go beyond our own perspective to infer the thoughts, beliefs, and feelings of other people. This innate skill to appreciate perspectives distinct from our own allows us to function effectively within the social world. For example, we can instinctively understand how a colleague may feel when their latest publication is rejected, or we can intuitively place ourselves in a friend’s shoes when they experience a joyous event like the birth of a first child.

Theory of Mind

My latest study sheds light on the brain regions that need to be functional in order to support this ability to empathise with others. The study, published in the journal Brain, reveals that structures in the right hemisphere of the brain are essential to enable us to read the minds of others and to consider their beliefs and feelings. ‘theory of mind’ is the term used to refer to our uniquely human ability to make these inferences and is crucial for our successful functioning in the social world.

By understanding that other people think and feel in ways that are distinct from our own perspective, we can appreciate differences between individuals. This capacity to infer the mental state of others confers immense flexibility in our approach to various social scenarios. Without this ability, we would appear rigid, egocentric, and unfeeling towards others.

While appreciating the mental state of others may come relatively easy to us, the capacity for theory of mind relies upon a complex network of structures in the brain. Research on healthy individuals has revealed that when we successfully consider another person’s psychological perspective, regions in the frontal, temporal and parietal lobes of the brain activate. Such widespread brain activation reveals how complex this function truly is.

It follows that damage to any one of these brain regions will block the capacity to take another person’s perspective. Theory of mind abilities are disrupted across a number of clinical conditions such as traumatic brain injury, autism, and dementia.

Semantic dementia

In frontotemporal dementia, it is commonly reported that patients are unable to understand how their actions affect other people, or to consider that the reactions of others may differ from their own. However, up until recently, we knew relatively little regarding the capacity for theory of mind in the syndrome of semantic dementia. My recently published research reveals, for the first time, that individuals with semantic dementia experience severe difficulties in considering the mental states of others, and that such deficits are attributable to atrophy of structures in the right hemisphere of the brain.

Semantic dementia is a subtype of frontotemporal dementia, characterised by the progressive loss of general knowledge about the world. It is conceptualised as a language disorder whereby patients experience a profound loss of the meaning of words and concepts. The patient is unable to recall the names of objects, places, people, and experiences difficulties in correctly labeling popular musical tunes, or basic emotional expressions. While the predominant complaint of the patient is that of language disruption, carers of patients with semantic dementia report alterations in social functioning and interpersonal behaviour.

The Protocol

Images taken from Lough et al. (2006) Neuropsychologia,

Images taken from Lough et al. (2006) Neuropsychologia,

I used a new task to explore if patients with semantic dementia could infer the thoughts, beliefs, and feelings of the main characters in humorous cartoon scenarios. Patients were asked to describe why a selection of cartoon scenes were funny and their descriptions were analysed for language that reflected consideration of different mental states, for example “he thinks”, or “she feels”. In the cartoon scene to the left, a correct answer would be something like, “The gentleman thinks he is being held up. The lady is not aware that she is frightening the man.”

A patient with semantic dementia tended to respond as follows, “The woman is hitting the man in the back. He is putting his hands in the air”. These responses indicated that the ability to spontaneously consider the mental state of others was disrupted in semantic dementia. Importantly, I demonstrated that the failure to successfully appreciate the viewpoints of others was not a result of the language difficulties that are typically found in semantic dementia.

Using neuroimaging analysis of structural MRIs, I found that shrinkage of the right temporal lobe of the brain underpinned the theory of mind deficits in semantic dementia. This finding is surprising, as these patients are typified by damage to the left side of the brain. As the disease progresses however, pathology spreads from the left to the right hand side of the brain. The semantic dementia patient displays impairments across multiple domains, beginning with language disruption and gradually progressing to include social dysfunction.

Why is this important?

The findings of this study are unique as they reveal, for the first time, that degeneration of right temporal regions in the brain is associated with social dysfunction in semantic dementia. The right temporal lobes have been consistently implicated in studies of social functioning in healthy individuals.

Our study illuminates the complexity of social cognition and how we achieve sophisticated acts of social inference in our everyday lives. By incorporating brain mapping techniques with new experimental tasks, we can continue to unravel the mystery of mind-reading and build a coherent picture of how humans navigate within the social world.

Is high cholesterol putting your brain at risk?

If you want to reduce your risk of Alzheimer’s disease, says Dr Scott Kim, be mindful of your cholesterol levels.

Notwithstanding the recent debate in the media, most of us understand that high cholesterol is harmful to your health because it can negatively affect your heart and arteries.

What you may not know, however, is that high cholesterol can also affect your brain; specifically, there’s growing evidence leading neuroscientists like me to suspect that high cholesterol may increase your risk of developing Alzheimer’s disease.

NeuRA's Dr Scott Kim is investigating the role of cholesterol in Alzheimer's disease

NeuRA’s Dr Scott Kim is investigating the role of cholesterol in Alzheimer’s disease

The growing evidence

Why do we suspect this? Firstly, we know that factors that increase your risk of developing heart disease – specifically, high blood cholesterol levels but also high blood pressure and a history of stroke and diabetes – also increase your risk of developing Alzheimer’s disease. Furthermore, there’s evidence that taking cholesterol-lowering drugs, called statins, decreases your likelihood of developing Alzheimer’s disease.

Another red flag is data from several animal studies suggesting a link between cholesterol and the production of amyloid-beta, the protein that accumulates abnormally in the brains of people with Alzheimer’s disease.

So how is it that high cholesterol increases your risk of Alzheimer’s disease? At NeuRA, we are trying to answer that question.

Cholesterol in the brain

Cholesterol is abundant in our brains; although the brain makes up only two per cent of body’s weight, it contains nearly a quarter of all the body’s cholesterol stores. Cholesterol has important jobs in the brain such as storing energy, acting as a structural component of the cell membrane and acting as a signalling (communication) molecule.

Cholesterol is transported out of cells by transporter proteins, and it’s these proteins – known as ABC transporters – that are the main focus of our research.

Our work has shown that ABC transporters are key regulators of how much cholesterol is inside brain cells. Just recently, we demonstrated that deleting a specific ABC transporter, called ABCA7, in a mouse model of Alzheimer’s disease caused significant increases in amyloid-beta levels. We suspect that the ABCA7 transporter facilitates the clearing of amyloid-beta from the brain. This is direct evidence that ABCA7 is crucial in the development of Alzheimer’s disease.

It’s important to understand what’s happening at a molecular level in Alzheimer’s disease so that we can discover new targets for drug treatments. By understanding the role of ABCA7, we may be able to learn how to inhibit the build-up of amyloid-beta protein and therefore provide potential therapeutic avenues for the treatment of Alzheimer’s disease.

In the meantime…

In the meantime, what can you do in terms of cholesterol to decrease your risk of developing Alzheimer’s disease?

Although controlling cholesterol levels in the brain by altering what you eat is generally very difficult, you can lead a healthy lifestyle and reduce foods in your diet that contain high levels of saturated fat. This will help to reduce the risk factors associated with Alzheimer’s disease that I mentioned earlier on.

Apart from healthy eating and regular exercise, keeping your brain active is also helpful. If playing games, writing a letter or simply interacting with others sounds easy (and it is!), then don’t delay – as the saying goes, ‘use it or lose it’!

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

“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.

 

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.

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!

Mental time travel – insights from semantic dementia

At NeuRA, we work with patients who have a form of younger-onset dementia called semantic dementia (SD). These patients experience progressive damage to a specific region of the brain called the temporal lobes; as a result, they forget the names and functions of simple objects and lose the ability to recognise familiar faces or popular tunes.

NeuRA’s Dr Muireann Irish

Despite these profound difficulties with naming and comprehension, SD patients perform well on tasks where language is not required, such as visual memory and spatial navigation tasks. They also remember events from their recent past with a surprisingly high level of detail. When it comes to imagining the future, however, SD patients have striking difficulties.

This ability to mentally travel through time represents a uniquely human activity; we frequently withdraw from the current moment to reflect upon our past or to imagine upcoming events in the future. Research has revealed that we use a widespread brain network to accomplish these complex acts.

Our work with patients with semantic dementia has allowed us to tap into this network and pinpoint the key regions in the brain essential for imagining the future.

Key regions of the brain implicated in remembering the past, and imagining the future. Taken from Irish, Piguet and Hodges (2012). Nature Reviews Neurology, 8, 152-161.

Semantic dementia patients cannot envisage their future

In a recent series of studies, we asked participants to remember past events from the last year and to imagine possible future events within the next year. While patients with SD could remember recent past experiences at a high level, they showed profound impairments when envisaging the future.

When we related patients’ task performance to their structural MRI brain scans, we found that these deficits in future thinking associate exclusively with damage to the anterior temporal lobes. This brain region is essential for our ability to store general world knowledge.

Typical pattern of brain atrophy in semantic dementia. In this image, we can see the classic left-sided atrophy in the anterior temporal lobe and temporal pole, regions crucial for general knowledge of the world around us.

Piecing together the evidence, this study suggests that general knowledge is essential for our ability to imagine events in the future.

The quality of future thinking in semantic dementia

In a second study, we investigated the quality of the future events imagined by our SD patients. We instructed participants to rate their remembered (past) and imagined (future) scenarios for level of detail, emotionality, and personal significance.

Not surprisingly, the imagined future events contained fewer details than their memories of past events. Interestingly, however, our SD patients rated these future events to be as detailed, emotionally strong and personally significant as the past events.

The inability to imagine the future in semantic dementia arises due to damage to the left anterior temporal lobe. This region of the brain is believed to underpin our knowledge of concepts, and therefore can be thought of as the brain’s general knowledge store. Taken from Irish and Piguet (2013). Frontiers in Behavioural Neuroscience, 7: 27.

What we found from this study was that despite a profound inability to imagine future events, the subjective experience of SD patients remains remarkably consistent across past and future contexts.

Importantly, these patients tend to ‘recast’ old events into the future rather than create novel experiences. Thus it appears that general world knowledge is essential for our ability to imagine not only the future, but to confer novelty and detail to these events.

Future directions

This series of studies gives us important insights into how we engage in complex feats of thinking.

What remains unknown, however, is the impact of future thinking difficulties in patients with dementia on an everyday level. If a patient with dementia cannot imagine the outcome of certain actions, for example, does this mean that they are more likely to engage in risky decisions?

Our next step will be to investigate how an inability to imagine the future affects patients, and their caregivers, in everyday life.

New dementia detection app

Just this morning I received an email about a new app for my mobile phone, developed by an American university, to screen for autism in babies and young children.

Like most people, I’m a sucker for looking up medical information on the internet when I’m worried. While I try to stick to reliable sources, it’s incredibly easy get a diagnosis from Dr Google that’s either inaccurate or just plain wrong. Add to that the fact that I’m a new mother, and my late night internet searches are a recipe for large doses of (usually) pointless worry.

Which is why the advent of apps that offer a reliable way of testing for certain disorders is such an encouraging development.

In just a few weeks, we will be able to access an app developed by NeuRA’s Prof John Hodges and colleagues from the UK to screen for dementia. The app is based on the Addenbrooke’s Cognitive Examination or ACE, the gold standard test for screening patients with potential dementia.

 

ACEmobile App

Originally a pen and paper test, the ACEmobile app has been designed for use on iPads and is self-scoring, meaning that very little training is required to use and administer the test. This also means that it’s reliable, something that’s often sorely lacking in the digital world.

The app will primarily be used by psychologists, nurses and other health professionals so  they can provide a report to clinicians – one that’s easy to interpret and allows comparison with what is considered a normal score in healthy older people.

The greatest benefit of this app and other future forays of this kind into the digital world is that health care professionals can detect dementia early and accurately – and not just those professionals in specialist centres (where patients often face long waiting periods) but those working in the community as well.

I’ve met families who struggled for many months wondering why the behaviour of their mother, father, uncle or grandmother had changed and if there was anything they could do about it. Being offered early diagnosis would have meant a world of difference to them, if only to have an explanation of what was going on.

Going forward, early diagnosis is going to become increasingly important as treatments for dementia improve. Having witnessed firsthand the hard work of researchers at NeuRA – along with their colleagues around the world – I have every faith that new and better treatments are not far off.

If you’d like to access the app, watch this space.

Could immunological mechanisms trigger neurodegeneration in frontotemporal dementia?

Dr James Burrell researches frontotemporal dementia. One of the symptoms of this type of dementia is forgetting language and words, which can be tested by asking a volunteer to name toy animals.

Frontotemporal dementia (FTD)  is the second most common degenerative disease causing dementia in younger adults, with onset typically occurring in the 50s or 60s. In FTD, damage to brain cells begins in the frontal and/or temporal lobes of the brain, which often results in personality and behavioural changes or losing the ability to speak or understand language.

When conveying a new diagnosis of frontotemporal dementia the clinician almost invariably encounters the following questions “Why has this happened?” “Is there any treatment?” and “Will our children get it?”.

Recent discoveries of genetic causes in familial FTD have given us a much firmer handle on the last question, and have undoubtedly shed light on the cellular processes leading to the death of brain cells in people with familial FTD. Nonetheless, we still know little about causation in non-familial FTD, which accounts for around 90% of cases. Without a clear understanding of these processes it is hard to visualise the development of an effective treatment for this devastating disease.

One potential avenue of exploration is the role of inflammation and the immune system.(2) Recently, Miller et al (3) reported the prevalence of autoimmune disease in two FTD subtypes in which the underlying pathology is quite predictable. The authors reviewed cases files seeking evidence of autoimmune diseases in these two FTD subtypes. A history of non-thyroid autoimmune disease was roughly 3-4 times more common in the FTD disease groups compared to controls or patients with Alzheimer’s disease. A second aspect of the study involved the measurement of an inflammatory marker in the blood, which was found to be elevated in both groups compared to controls, reinforcing the apparent association of neurodegeneration and immune disease. A wide variety of non-thyroid autoimmune diseases contributed to the elevated prevalence in the two groups. Why were only non-thyroid autoimmune diseases more common in the FTD subtypes? The answer may be found in examining so-called “clusters” of autoimmune disease, which may partly represent the expression of certain genetic factors.(4)

The study offers a tantalising clue but much remains to be understood. Is this apparent increase in autoimmune disease only true for one of the pathological processes that underlie FTD? If so, could measuring inflammatory blood markers help identify individuals with that pathology in other FTD subtypes, where the pathology is more varied? What is main determinant in non-familial disease: autoimmunity or systemic inflammation more generally? What is the relationship between FTD pathology and autoimmunity: which is the chicken and which the egg? Could immune modulation offer a route to disease modification? We hope that this important paper opens the way to a more complete understanding of the processes underlying neurodegeneration in FTD and the development of new therapies, which are needed desperately to halt the progression of this dreadful disease.