Frontotemporal dementia


Understanding the brain changes involved in frontotemporal dementia


Frontotemporal dementia (FTD) is the second most common degenerative disease causing dementia in younger adults.

The age of onset is typically in the 50s or 60s but can be as young as 30. The disease is sometimes called frontotemporal lobar degeneration and was first described 100 years ago by Arnold Pick and was previously referred to as Pick’s disease.

Damage to brain cells begins in the frontal and/or temporal lobes of the brain. When the initial damage is in the frontal lobe (called behavioural-variant FTD) the main changes are in personality and behaviour. Individuals with damage predominantly in the temporal lobe (either progressive non-fluent aphasia or semantic dementia) lose the ability to speak or understand language.

Our research is investigating the cognitive, behavioural, psychological and physical brain changes associated with frontotemporal dementia, as well as the impact of the disease on the lives of patients and their families. We are also looking at the genetics of frontotemporal dementia, and are currently conducting animal studies and designing a clinical trial of a potential treatment to slow the disease.


Severity rating scales

We have developed a rating scale that will allow professionals to give better advice to families and patients, and will permit patients and families to make adjustments to their living arrangements.

Episodic memory in FTD

Associative memory in frontotemporal dementia
Associative memory processes are crucial to the formation and retrieval of memories. Associative memory deficits in patients with FTD have not been thoroughly investigated. The aim of this project is to assess associative memory abilities in patients with different subtypes of FTD, patients with Alzheimer’s disease and healthy controls. We are utilising a number of novel associative memory tasks in an attempt to identify subtle deficits in associative memory abilities in these groups. Such tasks may be useful clinically and contribute to improving the diagnostic accuracy of patients with dementia in the early stages of the disease.
Episodic future thinking in frontotemporal dementia
Imagine the next time you will take a holiday abroad. What will you do in a few hours? What will you do next week…next month…next year? Thinking about the future, withdrawing from our current tasks to imagine, daydream, and construct possible future scenarios is something we all engage in. Imagining the future depends on the same neural system that is recruited when remembering the past. When dementia patients experience difficulties remembering the past, is their ability to imagine the future also affected? This study investigates episodic future thinking in frontotemporal dementia, to explore the impact of damage to the episodic memory system and how this affects the ability to conceive of oneself in the future.

Emotion processing in frontotemporal dementia

Emotional memory in frontotemporal dementia
All memories are not created equal. Emotion has a powerful impact on memory with highly emotional events generally remembered with greater detail and vividness than events that lack emotion. The brain regions necessary for both emotion and memory are affected in frontotemporal dementia. Although disturbance of emotion has been reported in frontotemporal dementia, whether it also impacts on memory has not been investigated. This project aims to determine how these emotion and memory interact in FTD, and how they differ across subtypes.
Emotion processes in FTD subtypes
How people interpret and recognize emotions in others is critical for everyday social interactions and the formation and maintenance of interpersonal relationships. Evidence now suggests that the ability to recognise emotions in others is disturbed in frontotemporal dementia. This project aims to investigate how emotion processing is disturbed across subtypes of frontotemporal dementia and determine whether there are ways to improve emotion recognition in these groups. This will help us to understand the mechanisms important for emotion processing, and help to find ways for patients and their families to overcome these difficulties

Eating disturbance in FTD

Marked eating disturbances (e.g., overeating) are common in a subset of patients diagnosed with FTD. Such behaviours have a major impact on patient management and health but their biological causes are poorly understood. Whether the hypothalamus, a structure critical for the regulation of eating behaviours, is affected in FTD is unknown. This project will investigate biological markers of eating disturbance in FTD using blood tests and high resolution neuroimaging.

Brain imaging

Patterns of white matter changes in frontotemporal dementia subtypes

Brain atrophy is found in specific cortical and subcortical regions in frontotemporal dementia. The pattern of atrophy is specific to each subtype. Although changes in the brain grey matter are well documented, changes in the white matter are not as well understood. This study investigates changes in white matter in FTD subtypes using diffusion tensor imaging, and how these changes are related to those found in the grey matter. This project will also map the evolution of these changes with disease progression.
In vivo and postmortem relations of white matter changes in frontotemporal dementia

Changes in white matter integrity have been reported in FTD on neuroimaging investigations such as MRI, with a particular interest on diffusion tensor imaging (DTI) in recent years. DTI provides a measure of tissue organisation. However, the nature of these changes of the white matter ultrastructure in FTD is unknown. This project will determine the changes in the brain white matter at postmortem in FTD patients for whom DTI was acquired in life. Relations between these changes in the different FTD subtypes will be established.

Biological basis of episodic memory

Functional and biological correlates of associative memory

Our ability to create and retrieve specific memories is dependent upon a number of discrete cognitive processes allowing us to create associations between different types of information. These processes are collectively called associative memory. Recent evidence suggests that brain structures within the medial temporal lobe are crucial for different types of associative memory. This project utilises different tasks of associative memory in combination with structural and functional magnetic resonance imaging techniques to investigate the neural correlates of associative memory processes. The goal of this research is to increase our understanding of the contributions of the medial temporal lobe contribute to these processes.

Contributions of prefrontal cortices to episodic memory

Episodic memory refers to our ability to remember events that are located in a particular time and place, for example where you left your car keys, or recalling your first day at school. The importance of the medial temporal lobes (MTL) for forming and retrieving episodic memories is well established, however, less is known regarding the role of the prefrontal cortex (PFC) or the possible interaction between these brain regions. This project investigates episodic memory disruption in frontotemporal dementia, a neurodegenerative disorder affecting both temporal and prefrontal brain regions selectively, providing us with a unique model to investigate the specialised roles of the MTL and PFC in episodic memory and how these systems interact.

Causes, consequences and costs of injury-related hospitalisations for people with dementia: identify

This research program explores the influence of dementia on the pattern of hospital admissions, clinical care, health outcomes and economic costs of older people with an injury-related hospitalisation. It provides data on the impact of injury on a person with dementia and the health system more generally.

Preventing Falls in Older Adults with Cognitive Impairment or Dementia (IFOCIS)

The IFOCIS study aims to determine the ability of an individualised exercise and home hazard reduction program to reduce the rates of falls in older people living in the community with cognitive impairment or dementia. To do this, we have two groups– an ‘intervention’ group and a ‘control’ group. The Intervention program involves: an exercise program and a home hazard reduction program delivered by experienced therapists tailored to the participant’s cognitive and physical abilities. Carers are an integral part of the intervention team, as some participants require supervision for exercise sessions. We work with carers to help them understand how to get the best from the participant they are caring for, in terms of their ‘functional cognition’, completing the exercises and preventing falls.

Taking this individual approach means that participants can have very different cognitive abilities and still be included in our study. No other study has done this to date.

All participants will undergo an assessment at baseline with re tests at 6 and 12 months to compare each of these groups on things like strength & balance. The primary outcome is the rate of falls during the 12 month study period which is collected using falls diaries on a monthly basis.

Recruitment for this project is now complete. We are in the process of analysing the data and submitting this work for publication. We hope to have results available soon, please visit again for an update.

Statistical Analysis Plan

Frontotemporal dementia and motor neurone disease

This project’s objective is to develop cell culture and mouse models to study underlying pathomechanisms and develop/test new treatments.

Positional cloning of a chromosome 16 dementia / motor neurone disease gene

The aims of this project are to undertake the biological characterisation of this novel neurodegeneration gene. We are also examining a panel of commercially available and clinically relevant agonists and antagonists to modulate key pathways involved in Alzheimer’s disease and other neurodegenerative disorders.

Eating and metabolic changes in FTD and MND

We have looked at the impact of overeating on body weight, cholesterol and insulin levels and relating all of these changes to regions of brain pathology as demonstrated by MRI imaging. We are now extending these studies to investigate patients with motor neurone disease and with Alzheimer’s as well as those at risk of genetic FTD.

Neuropathology of frontotemporal dementia

Unlike other neurodegenerative conditions, people with FTD may have one of a number different underlying cellular brain changes. Patients followed longitudinally in life are enrolled into the brain bank so that we can gain insights into the pathological processes in FTD.

Identifying biomarkers in frontotemporal dementia

In order to develop treatments and effective interventions for patients with FTD, the underlying process of brain degeneration needs to be identified early in the disease course. We are investigating protein changes in blood specimens that may tell us about the underlying brain pathology in FTD.

Genetics of frontotemporal dementia

The laboratory at the NeuRA are conducting longitudinal studies of the first degree relatives of people with these known mutations who are at risk of developing the disease to find the earliest brain changes. We are also looking for new genes responsible for families with FTD & MND. We hope these genetic studies will open doors to a better understanding of the biology of FTD, and eventually treatment.

Deficits in emotion processing and autobiographical memory and their impact on carers

How is the processing of emotion impaired in FTD? How does it affect the ability to remember meaningful and important information from one’s life? How does it affect interpersonal relationships? How do these deficits evolve with time? These are some of the questions Professor Hodges and his team are trying to answer in this research project.

Coping with everyday life disabilities

We are interested in understanding the difficulties patients face in their everyday routines, and why these difficulties occur. Our aim is to develop strategies to overcome these difficulties impacting on everyday life and limit the impact of this disease in both patients’ and families’ lives.

Advancing knowledge on FTD by using a range of research methods

Professor Hodges and his team of researchers aim to advance knowledge on a broad front by using a range of research methods (neuropsychology, behavioural measures, brain imaging, etc) to improve the care, management, and treatment of FTD.

What else is happening in Frontotemporal dementia research at NeuRA?