Clinical syndromes

Clinical Syndromes

For a brief up to date review of the clinical syndromes of FTD read this paper by Rhian Convery from our team. For a more detailed review, read this paper by Ione Woollacott from our team.

In this section we will look at the following clinical syndromes:

Behavioural variant FTD

BvFTD is the most common variant of FTD.

The 2010 criteria for diagnosis of bvFTD require 3 out of the following 6 symptoms to be present:

  • disinhibition
  • apathy
  • lack of empathy
  • obsessiveness
  • altered food preferences
  • executive dysfunction

Importantly, these changes in behaviour and personality must progress over time in order to make a diagnosis.

Looking at each of these in more detail:

  • Disinhibited behaviour includes embarrassing social interactions, impulsivity, excessive spending, and gambling.
  • Apathy describes a decreased interest in engaging in social situations or activities that one previously found enjoyable.
  • Individuals that lack empathy are unable to read the emotions of others or understand their experiences.
  • Obsessive behaviours that arise can be simple repetitive movements such as tapping, scratching, and rubbing, whilst more complex ritualistic behaviours include hoarding, cleaning rituals, and fixed walking routines.
  • Dietary changes can range from binge eating to odd food preferences and are frequently associated with cravings for sweet foods.
  • Executive dysfunction includes difficulty planning, problem solving, being flexible in thought, and making decisions.

Almost all people with bvFTD also develop difficulties with social cognition, which includes problems with understanding the thoughts and feelings of others.

Although executive dysfunction and impaired social cognition are the main forms of thinking problems in bvFTD, some people develop difficulties with:

  • semantic memory – knowledge of words and concepts
  • language – often decreased speech output or difficulties communicating
  • episodic memory – forgetting recent events or difficulties with maps and directions
  • face recognition – known as prosopagnosia

A lack of insight is a common feature in bvFTD, as people fail to recognise the changes in their behaviour, personality and thinking. Consequently, they rarely seek medical advice, and are often diagnosed due to a relative or colleague suggesting an appointment. People can become annoyed or agitated when questioned about their symptoms as they feel there is nothing wrong with them.

In addition to altered behaviour, psychiatric symptoms can present in a minority of people with bvFTD. These include:

  • anxiety
  • delusions
  • visual hallucinations

More recently it has been recognised that other symptoms can be seen in people with bvFTD including:

  • a change in response to pain
  • an impaired ability to regulate temperature – this can lead to people wearing inappropriate clothes for the weather such as coats in summer or short-sleeve shirts in winter
  • sleep disturbance and excessive daytime sleepiness

BvFTD can be difficult to diagnose for numerous reasons. Changes in behaviour can be very subtle initially, and therefore considered ‘normal’, particularly when they seem like an exaggeration of a previous personality trait. Other symptoms of bvFTD overlap with psychiatric disorders or those seen in Alzheimer’s disease and can therefore lead people to make the wrong diagnosis.

Lastly, it is important to note that there are some people (commonly men in their 60’s or 70’s) who present with behavioural symptoms similar to bvFTD but without any cognitive deficits and lacking any changes on brain imaging. Whilst partners and family members may feel that symptoms are progressive over time, there are commonly few abnormalities found when assessed by a clinician. These patients are often described as having a bvFTD ‘phenocopy’ syndrome – in other words a disorder presenting very similarly to bvFTD. The majority of people fitting into this group do not have a degenerative illness. Exactly what condition people do have remains unclear but it may represent worsening of a previous longstanding neuropsychiatric illness such as an autistic spectrum or personality disorder.

Primary progressive aphasia

The term PPA describes a group of disorders in which language impairment is the main symptom at the start of the illness.

There are three criteria that should be fulfilled for all PPA disorders:

  • the insidious onset and gradual progression of aphasia affecting at least one of: speech production, the ability to name things, understanding of words, and grammar.
  • language difficulties must be the only thing that affects people’s daily living activities
  • the disorder can only be explained by a neurodegenerative process and not by any other medical condition

It is essential to meet all of these criteria to make a diagnosis of PPA as speech and language disorders can also arise due to cerebrovascular conditions or other neurodegenerative disorders.

Individuals with PPA can also have behavioural deficits that are similar to bvFTD, however, these tend to develop later on in the disease.

Once these criteria have been satisfied, people can then be diagnosed with one of the three PPA variants:

  • semantic variant (svPPA), or semantic dementia
  • nonfluent variant (nfvPPA), or progressive nonfluent aphasia
  • logopenic variant (lvPPA), or logopenic aphasia

A subset of patients with PPA do not fulfil the criteria for any of these three variants, and have been classified as PPA – not otherwise specified, or PPA-NOS. They have also been called a ‘mixed’ PPA. For these people, the clinical syndrome may become clearer throughout the disease course, where they can then be sub-diagnosed, or in many cases it may remain unclassifiable.

Each of the main PPA subtypes presents with specific language problems and is associated with involvement of distinct parts of the brain:

The main problem in svPPA is loss of semantic knowledge or semantic memory. This describes our ability to understand ideas and concepts.

The first symptoms usually arise because of problems with verbal semantic memory – our knowledge of words and their meanings. This can lead people to develop difficulty finding the right words when they are speaking.

When tested in a clinic there may be difficulties with:

  • describing pictures – speech may be fluent but vague and lacking in words that describe the picture.
  • naming of pictures or objects – called anomia, people may initially lose uncommon or less familiar words before losing more common words e.g. being unable to name ‘labrador’ and only later on losing the word ‘dog’.
  • using the correct word – people may use semantic paraphasias, saying a related word with a different meaning e.g. saying ‘fork’ instead of ‘spoon’.
  • understanding the meaning of words
  • reading – people develop a surface dyslexia, being unable to read irregularly spelt words e.g. saying ‘sew’ as ‘soo’

Later on, people develop difficulties with visual semantic knowledge, called an associative agnosia. This leads to people being unable to recognise objects. Some people may develop difficulty recognising faces, called prosopagnosia.

More recently, we have recognised that people also have difficulties with their auditory (hearing), gustatory (taste), and olfactory (smell) semantic knowledge. People may describe problems with being confused about what they have heard, or not knowing whether something is edible or not.

Behavioural changes can also be a prominent feature of svPPA, with a range of behaviours similar to those seen in bvFTD. In particular, people may become obsessive over things such as daily routines, and may develop eating problems such as developing a sweet tooth.

The main problem in nfvPPA is nonfluent speech due to one or both of agrammatism or a form of effortful speech production called apraxia of speech.

Agrammatism describes a number of incorrect ways in which people may speak or write:

  • missing out words within sentences, often the small ‘function’ words like ‘of’, ‘and’, ‘the’.
  • inappropriate ordering of words within sentences.
  • putting the wrong endings on words e.g. using a plural rather than a singular word, such as ‘men’ for ‘man’
  • using the wrong tense, e.g. ‘went’ rather than ‘go’.

These problems can lead people to use short, simple phrases, often called ‘telegraphic’ speech. Agrammatism can also lead to people having difficulties in understanding complex sentences. If agrammatism is the main or only symptom, some people call this form of PPA, agrammatic variant PPA, or agrammatic aphasia.

Apraxia of speech describes the inability to coordinate the motor aspects of speech production. Speech becomes hesitant and effortful, and people may struggle to articulate the correct sounds. Speech may be slower and words may sound distorted or contain the wrong sounds, called phonemic paraphasias, e.g. ‘aminal’ instead of ‘animal’. People may also develop problems with co-ordinating movements of the mouth, called orofacial apraxia. If apraxia of speech is the main or only symptom, some people call this condition, progressive apraxia of speech.

However, most people tend to develop both agrammatism and apraxia of speech over time.

Some people with nfvPPA can develop binary word reversals, where they say the opposite word from what they intend to e.g. ‘yes’ instead of ‘no’ (or vice versa). We often call this the ‘Dibley’ phenomenon after the character in the UK television sitcom ‘The Vicar of Dibley’ who does something similar.

People may respond to questions with ‘stock phrases’ such as ‘I don’t know’. Speech can also sometimes be replaced by non-verbal vocalisation such as laughter. Over time, speech can deteriorate to the point where there is no speech present, called mutism.

People may develop problems with reading and writing, and later on develop problems with executive function e.g. difficulties with planning and problem solving.

Behavioural changes tend not to be very prominent in the majority of people with nfvPPA. However, there are a minority of people where the range of behaviours seen in bvFTD are present. In the majority, there are often mild behavioural symptoms as the disorder progresses.

The main problem in lvPPA is the presence of long word-finding pauses in speech. Unlike nfvPPA, articulation and grammar are normal.

When tested in a clinic there may be difficulties with:

  • naming of words, although not as severely as in svPPA
  • repetition of sentences more than individual words, particularly longer sentences
  • comprehension of sentences, particularly longer sentences
  • digit span, the ability to hold a string of numbers in mind and then repeat them back
  • reading, particularly new words, called a phonological dyslexia

As lvPPA progresses, people develop problems with:

  • calculation, or dyscalculia
  • co-ordination of movements of the arms, called limb apraxia
  • episodic memory
  • spatial awareness

Although this disorder is part of the PPA spectrum, it is usually described as an atypical presentation of AD, rather than a subtype of FTD. Some people call it the language variant of Alzheimer’s disease.

Atypical parkinsonian disorders

‘Parkinsonism’, or a ‘parkinsonian disorder’, or an ‘akinetic-rigid syndrome’ all describe a set of symptoms similar to those seen in Parkinson’s disease. The key symptoms are those of slowness or lack of movement (bradykinesia or akinesia) and stiffness (rigidity).

Around a third of people with FTD develop parkinsonism, particularly those with bvFTD and nfvPPA. However, parkinsonism is rare in people with svPPA or lvPPA, and almost never occurs in those with associated MND.

Some people with FTD develop parkinsonism that does not fit neatly into a diagnostic category. Other people may develop symptoms that fit into one of two particular ‘atypical’ parkinsonian disorders called corticobasal syndrome, CBS, and progressive supranuclear palsy, PSP.

Each of these forms of parkinsonism responds less well to levodopa therapy than Parkinson’s disease itself. For a review of drug therapies that are given in CBS and PSP read this paper.

This condition used to be called corticobasal degeneration or CBD, but nowadays the term CBS is more commonly used to distinguish it from a particular form of tau pathology that is also called CBD.

The diagnostic criteria for CBS describe an asymmetric disorder of movement combined with other symptoms. As well as stiffness (rigidity) and slowness (akinesia) the core features are the following:

  • holding the limbs in an abnormal posture – dystonia
  • sudden jerking movements of the limbs – myoclonus
  • inability to do complex actions with the limbs – limb apraxia
  • inability to do complex actions with the mouth and face – orofacial apraxia
  • difficulty discriminating certain sensations – cortical sensory deficit
  • the limb seeming to move on its own – alien limb phenomena

The current diagnostic criteria recognise that CBS overlaps with:

  • bvFTD
  • nfvPPA
  • PSP

Each of these clinical syndromes may occur either before or after the onset of symptoms of CBS.

PSP is a condition with four core features:

  • poor balance, resulting in backwards falls – postural instability
  • impairment of looking up and down – vertical gaze palsy, or ocular motor dysfunction
  • slowness, including difficulty walking with freezing of gait – akinesia
  • cognitive impairment, with usually either speech and language difficulties or executive dysfunction

Other features include:

  • articulation problems – dysarthria
  • swallowing difficulties – dysphagia
  • intolerance to light – photophobia

This collection of symptoms is the most common presentation of PSP, and is also sometimes known as Richardson’s syndrome, or PSP-RS.

However, the recent diagnostic criteria have established a number of variants of PSP including:

  • people that present with symptoms similarly to Parkinson’s disease (PSP-P)
  • people who have mainly difficulty walking, called gait freezing (PSP-PGF)
  • people with predominantly eye movement problems, called ocular motor dysfunction (PSP-OM).

The new criteria also recognise the overlap with FTD. If the first presentation is bvFTD or PPA with only later development of PSP symptoms then the new criteria call the syndrome:

  • PSP-F, for a frontal or behavioural presentation
  • PSP-SL, for a speech and language presentation, usually similar to nfvPPA

Helpful clinical resources for both CBS and PSP include:

FTD with motor neurone disease

Motor neurone disease or MND is a disorder of the nerves that control the body’s motor function. It affects the nerves that go to the muscles in the arms and legs, and that allow people to speak and swallow. It is also known as amyotrophic lateral sclerosis or ALS.

MND may present either before or after the symptoms of FTD. In other words, some people who have MND as their first symptom may go on to develop FTD. Similarly, some people who have FTD as their first symptom may go on to develop MND.

Around 10-20% of people with FTD develop MND: this is known as FTD-MND or FTD-ALS. It occurs usually in people who have behavioural variant FTD and is less common in people with nfvPPA. It is very rare in people with svPPA.

Around 15% of people with MND develop FTD: this may be known as MND-FTD or ALS-FTD when it occurs this way round. Milder cognitive and behavioural abnormalities not meeting the criteria for FTD are also reported in 50-70% of people with MND – the revised Strong criteria describe people with:

  • MNDci or ALSci – people with cognitive impairment
  • MNDbi or ALSbi – people with behavioural impairment
  • MNDcbi or ALScbi – people with cognitive and behavioural impairment

The overlap of FTD and MND occurs more commonly in people who have a mutation in the C9orf72 gene.

In people who have FTD-MND, symptoms may progress more rapidly than in those people with FTD alone, although this is not the case for every person.

Symptoms vary from person to person, but can include:

    • Wasting and weakness of muscles
    • Twitching of muscles – called fasciculations
    • Stiffness of muscles
    • Problems with articulation such that the speech may sound slurred
    • Problems with swallowing
    • Impairment of breathing

Helpful clinical resources which we were involved in developing can be found at the MND Association website.

The MGH FTD Unit in Boston, USA, have a YouTube channel which often has helpful videos about the FTD clinical syndromes.

We helped to develop an online learning course which has one module about bvFTD: The Many Faces of Dementia.

The Eastern Cognitive Disorders Clinic in Melbourne, Australia has an ‘FTD Toolkit‘ which has some useful modules about FTD.

A list of webinars and books about FTD can be found on the AFTD website.