Introduction

Overview of frontotemporal dementia

Dementia is a syndrome, or collection of similar symptoms, linked to a progressive impairment in brain function. This includes memory loss, personality changes, and difficulties in social interactions and daily activities. It has many distinct causes and types – including frontotemporal dementia (FTD). FTD, formerly known as Pick’s disease, is a type of dementia that impacts the nerve cells (known as neurons) in the frontal and temporal lobes of the brain.¹ Whilst the frontal lobe is responsible for higher functioning processes (i.e. expression of language, problem-solving, and critical thinking) and is localised at the front of your brain, the temporal lobe resides behind your ears, and thus processes any auditory information and is accountable for memory and language.² Dysfunction or deterioration in these areas results in changes to personality and behaviour, difficulties in speech and language learning, problems with mental abilities, and physical health issues.³

Anatomical structure of the brain. Source: National Institute of Ageing.

It is estimated that FTD accounts for less than 1 in 30 dementia cases, which equals approximately 31,000 people affected by FTD in the UK. While there are variations in the age at onset, symptoms often present between the ages of 45 to 64 – although individuals who are younger or older than this range can still be affected. 

There are 3 main types of FTD: behavioural variant frontotemporal dementia, primary progressive aphasia, and frontotemporal dementia with motor neurone disease.⁴

Behavioural variant frontotemporal dementia (bvFTD)

Alters behaviour, judgement, and personality. Some specific examples include:

• Acting impulsively or inappropriately
• Losing motivation 
• Exhibiting obsessive behaviour such as repeating the same word or activity

Primary progressive aphasia (svPPA)

Aphasia refers to having difficulty in communicating. It has 2 subtypes: 

• Nonfluent variant primary progressive aphasia (nfvPPA): Results in a person having difficulty finding the right expression or maintaining a conversation
• Semantic Aphasia: Affects how an individual understands language i.e. loss of vocabulary

Frontotemporal dementia with motor neurone disease (FTD-MND)

Motor neurone disease is a neurological disorder that causes the deterioration of the motor system, which controls movement. FTD-MND patients experience muscle weakness and eventually paralysis. This may cause difficulties in everyday functioning, such as eating and using their hands. For some individuals, the physical changes (MND) occur first, whereas for others, the mental alterations (FTD) occur first.

Importance of early detection and diagnosis

There are no treatments to delay or cure FTD or the progression of the disease. As a result, it is important to detect FTD as early as possible to ensure that the symptoms of whichever FTD variant can be easily managed. Unfortunately, the diagnosis of FTD is quite challenging due to its similarity in symptoms to other conditions. To elaborate, FTD is a rare form of dementia; this means that patients who suffer from this are more likely to be misdiagnosed as having other neurological diseases such as Parkinson's disease, vascular dementia, or Alzheimer's disease. Those who suffer from early bvFTD may be subjected to a mood disorder diagnosis, such as depression. Therefore, it is important to have extensive examinations of the brain to ensure that misdiagnosis can be avoided. 

Neuroimaging in FTD

Research, care, and diagnosis of FTD all heavily rely on neuroimaging. Neuroimaging is a non-invasive method which captures detailed images of the brain. This can be split across broad categories, including structural and functional imaging. Whilst structural imaging such as magnetic resonance imaging (MRI) allows the visualisation of the brain structures, functional imaging such as positron emission tomography (PET) measures a range of parameters when the patient is at rest or undertaking a specific task; this includes metabolic activity, blood flow, or haemodynamic changes. Both imaging modalities are used to safely understand the progress of FTD in the brain, and monitor it to ensure that the best treatment plan to treat symptoms can be followed.⁵  

MRI 

Magnetic Resonance Imaging (MRI) produces three-dimensional analytical images of the brain tissues using a magnetic field and radio waves. One way that MRI helps in the diagnosis of FTD is through observing brain atrophy patterns. Brain atrophy refers to the loss of neurons and/or the loss of the electrochemical connections between these (known as synapses). These are prevalent in the brain’s right hemisphere, which often displays more extensive atrophy than the left hemisphere.⁶

In addition, the brain atrophy patterns allow the differentiation between the subtypes of FTD, and the characterisation of the distinct types of dementia and other neurodegenerative disorders based on the regions that the atrophy patterns are more prominent in. To elaborate, previous research has demonstrated that high atrophy was found in the anterior cingulate cortex (involved in emotional regulation) in patients with bvFTD; whereas this was prevalent in the left posterior frontal lobe (crucial for the production of speech) in patients with nfvPPA.⁷ Similarly, scientists compared MRI scans of patients suffering from Alzheimer’s disease with patients that have bvFTD; they have found that there is an increase of atrophy in the thalamus and the striatum in the bvFTD group, as well as enlargement of the ventricles.⁸ These specific anatomical details enable healthcare experts to identify differences between the two neurodegenerative diseases, leading to a better diagnosis. 

Benefits and considerations

• Helpful for early and accurate diagnosis, and excluding other possible neurological diseases
• Excellent soft tissue contrast resolution
• Does not use radiation, which allows multiple scans to follow up on the progression of FTD
• Limitations in accessibility and slower scanning speed.¹ 

PET scans 

When structural imaging is inconclusive or not visible yet, positron emission tomography (PET) scans enable a clearer distinction. Similarly to MRI, PET scans can be utilised to differentiate between the subtypes of FTD by measuring the metabolic activity in the brain. Hypometabolism refers to a decrease of metabolic activity and intake of blood glucose in the brain. This is commonly linked to memory loss in many neurological diseases. Research indicates that hypometabolism is commonly associated with the perirolandic region, superior frontal gyrus, and precuneus.⁶ As the condition worsens, prefrontal areas, anterior temporal regions,  subcortical structures, and thalamic regions show extensive regions of decreased metabolism.⁹

Benefits and considerations

• Detect functional abnormalities before structural changes become visible
• Provides functional information about FTD and its subtypes
• Assists in treatment planning and response evaluation
• Limited spatial resolution and potential false-positive findings¹⁰ 

Future directions

Current research is being conducted in extensive longitudinal cohorts across distinct centres to test the advancement of multimodal MRI and PET imaging with specific molecules linked to the development of the disease. This will enable the research to be translated into clinical settings, where practitioners may be able to use a combination of these imaging modalities to treat patients. With the development of newer technologies and biomarkers (an objective measurement that records the state of a cell or an organism at a specific time/location), our understanding of FTD and its subtypes will eventually increase to accommodate and be able to recognise early signs of FTD, allowing the preparation of appropriate treatment strategies.^10,11

Summary

Frontotemporal dementia is an uncommon type of dementia which impacts an individual’s personality or behaviour. Neuroimaging modalities, such as MRI and PET scanners, play a significant role in the diagnosis of FTD, monitoring of the disease progression, and guidance of treatment plans. Both scans provide excellent functional information about the development of FTD. Whilst MRI provides insight into the anatomical structures of the brain, PET scans provide information about the metabolic activity of the frontal and temporal lobes. Integrating multiple imaging modalities allows for a more comprehensive evaluation, and as research is advancing with the development of suitable biomarkers and other imaging techniques, it is important to combine these together to ensure optimal management of FTD.