Introduction
Behavioural variant fronto-temporal dementia
Case 1: Probable early onset bv-FTD
Language variant fronto-temporal dementia
Case two: semantic dementia
Case 3: Progressive non-fluent aphasia
Discussion
References

Introduction

Fronto-temporal lobe dementia (FTLD) refers to a rather diverse group of neurodegenerative disorders that primarily affect the frontal and anterior temporal lobes of the brain. The onset is typically in the sixth decade of life, although significant variation in the age of onset exists. It is a common cause of early onset dementia with its associated socioeconomic and human cost.1

Three distinct clinical presentations of FTLD have been described – behavioural variant fronto-temporal dementia (bvFTD), progressive non-fluent aphasia (PNFA), and semantic dementia (SD). The latter two are sometimes grouped together and referred to as language variant fronto-temporal dementia.2

Each clinical syndrome has a distinct initial pattern of atrophy on structural neuroimaging, and distinct histopathological and genetic features also have been identified to some extent. Even though the clinical syndromes have distinct initial presentations, significant symptomatic overlap develops as these disorders progress and the underlying neurodegenerative process spreads.3

Behavioural variant fronto-temporal dementia

Behavioural variant fronto-temporal dementia (bv-FTD) presents with progressive and enduring changes to behaviour and personality, as well as apathy and disinhibition. This may manifest as socially and morally inappropriate behaviours such as inappropriate comments, increasing irritability and conflict, sexually inappropriate behaviours, and rarely physical aggression and gross criminal offences.4 Repetitive motor behaviours, hyperorality, and changes to dietary habits are also common in bv-FTD.5

Cognitive deficits are often subtle, and certain widely-used cognitive screening tools such as the Mini-Mental State Examination and the Addenbrooke’s Cognitive Examination (ACE) may fail to identify significant abnormality in cases of bv-FTD. A Frontal Assessment Battery is generally regarded to be more sensitive at identifying such cases, and patients with bv-FTD often demonstrate difficulty with set shifting, response inhibition, abstract reasoning, and executive tasks.6  Episodic memory, orientation, and praxis and more likely to be spared than in Alzheimer’s type dementia.7

Structural neuroimaging in bv-FTD shows bilateral frontal lobe atrophy, particularly in the dorsomedial and orbitofrontal regions. Functional neuroimaging shows hypometabolism and hypoperfusion in the same regions.8

Case 1: Probable early onset bv-FTD

A 37-year-old gentleman was referred to mental health services in 2016 with symptoms of low mood and increasing irritability. During his triage assessment the client described his mood as “not good” and he told the assessor that he gets angry and shouts at his friends and he cannot control it. This led to considerable interpersonal difficulties. The client also mentioned that he started having difficulty with certain activities of daily living, such as using the washing machine, filling in application forms, and holding conversations with people. The assessor remarked that he was unable to give details when asked open questions and that he “took his time to respond.” The client was an otherwise fit and healthy 37 year old who had only recently stopped working as a travel agent. He had no medical history of note.

The client was hence referred for a neurology review at a local hospital, and an MRI brain scan was requested. The scan showed significant left sided fronto-temporal atrophy, illustrated in Figure 1.

Whilst the neurology assessment was ongoing the client’s mood deteriorated further and he reported having intrusive thoughts of harming himself and his family members. He was therefore detained under the Mental Health Act to a local psychiatric hospital. He was treated with escitalopram and olanzapine and an improvement in his mental state was observed.

 

 

 

 

Figure 1: (a) Axial FLAIR slice illustrates bilateral frontal lobe atrophy, most marked on the left side.  (b) Sagittal T1 slice illustrates left sided frontotemporal atrophy.  Given that the patient is 37 years of age, this atrophy is considered severe.

 

Afew months lat er the client was assessed at a regional clinical neuroscience centre. He was described as being rather “child-like” during the assessment and made inappropriate comments. He had developed polydipsia and a preference for sweet foods, and had started to repeatedly and obsessively wash his hands. There were also reports of inappropriate sexual behaviour. His cognitive impairment also appeared to progress, and he dropped from 67/100 to 51/100 on the Addenbrooke’s cognitive examination in a few weeks. Performance on a Frontal Assessment Battery was described as “extremely poor,” with failure to identify similarities, failure to follow tapping commands, and unquestionably taking the examiner’s hands. A diagnosis of behavioural variant fronto-temporal dementia was made based on the neuroimaging findings and clinical presentation. No additional pharmacological treatment was prescribed.

The client has a possible family history of fronto-temporal dementia. His cousin on the maternal side of the family died aged 52 years old on a psychiatric ward from choking on food. The cousin had been diagnosed with bipolar disorder at the age of 40 years and continued to progressively decline since then. A post-mortem examination found a pathological degree of cerebral atrophy, most pronounced in the frontal lobes. C9ORF72 was postulated as a possible genetic link between the cases due to its incomplete penetrance, but the client tested negative for this genetic abnormality. He also tested negative for abnormal levels of very long chain fatty acids.

In late 2017, the client was placed in a care home but within a few weeks his behaviour became increasingly challenging and there were reports of him pushing people and spitting in their faces, as well going into other residents’ rooms seeking out food. He was subsequently admitted to an inpatient dementia care unit. Whilst an inpatient he continued to deteriorate and eventually became almost completely mute and dependent on staff for all activities of daily living including personal care. He also developed generalised epilepsy around this time. In 2018, he was discharged to a more specialised community placement. As of April 2019, he remains under the care of a community old age psychiatric team. He is currently immobile, has a significant degree of muscle stiffness, and is developing increasing swallowing difficulties. All psychotropic medication has been discontinued.

This case is noteworthy because the age of onset of symptoms of bv-FTD was significantly earlier than usual. The symptoms displayed by this client and their progression are otherwise quite typical of bv-FTD. Another interesting feature of this case is the positive family history but lack of a specific inheritance pattern, which poses difficulties in assessing whether other members of the family are at risk of developing this disorder.

Language variant fronto-temporal dementia

Semantic dementia and progressive non-fluent aphasia are two clinical sub-types of fronto-temporal lobe dementia that present with a decline in language abilities. Together, they account for around half of all cases of FTLD.1

Semantic dementia (SD) is a disorder characterised by the loss of semantic memory, which refers to general knowledge that a person accumulates over their lifetime. This includes knowledge of the meaning of words. Semantic memory is usually differentiated from episodic memory, the latter being memory for events that a person has experienced.1

Patients with semantic dementia usually present with a fluent type of aphasia, where syntax is preserved but the actual content of speech is rambling, circumlocutory, and often lacks the use of accurate words. The ability to understand spoken language is often impaired. Some patients display a more visual rather than verbal loss of semantic memory, and this manifests as difficulty recognising visual objects (visual agnosia) or faces (prosopagnosia).9

Semantic dementia has a consistent and characteristic pattern of features on neuroimaging. There is usually an asymmetric pattern of atrophy or hypometabolism affecting the antero-inferior temporal lobes. Predominantly left sided atrophy usually produces a clinical syndrome of verbal semantic memory loss, whereas predominantly right sided atrophy usually produces a clinical syndrome of non-verbal (visual) semantic memory loss.10

Progressive non-fluent aphasia (PNFA) is a clinical syndrome characterised by progressively worsening non-fluent speech, loss of syntax and grammar, and word finding difficulties. Speech often sounds telegraphic and the use of single word answers is common. The speech disorder may be associated with more general incoordination of orofacial muscles.11

Neuroimaging in cases of PNFA typically shows atrophy or hypometabolism in the perisylvian cortices on the dominant hemisphere.12

Case two: semantic dementia

A 68-year-old lady was referred by her GP for a specialist memory assessment after her daughter reported that she was having difficulty remembering information. She was also noted to be very anxious on interaction, and appeared to find it hard to follow a conversation. Her past medical history was quite unremarkable, with only a diagnosis of psoriasis and psoriatic arthropathy for which she takes sulfasalazine.

The client was initially seen by a psychiatrist in late 2017. During assessment she was found to have a profound difficulty understanding spoken language, however she remained quite functional within her daily life and could still adequately manage her finances, look after herself and her property, and drive without any mishaps. A significant mood or anxiety disorder was ruled out as part of the assessment. Cognitive examination was very limited by the patient’s inability to comprehend instructions, although she could demonstrate that she was still oriented to time and place. The client was subsequently referred on to neurology.

In the meantime, an MRI brain scan was requested. It was reported as showing asymmetric temporal lobe atrophy that is more severe on the left. On both sides, atrophy was more marked anteriorly with relative preservation of the posterior temporal lobes, as shown in Figure 2.

 

Figure 2:  (a) Coronal T1 slice indicates marked asymmetrical temporal lobe atrophy, most severe on the left side. (b) Axial T2 slice shows that the atrophy is most marked in the anterior temporal lobes with relative preservation of volume posteriorly. There is secondary compensatory enlargement of the temporal horns of the lateral ventricles.  These features are typical of semantic type of frontotemporal dementia.

 

When she was reviewed by a neurologist she once again presented as having severe difficulties with understanding language and also found it difficult to name objects. Her speech was fluent but she often used inappropriate words and was almost invariably out of point. A diagnosis of semantic dementia was therefore made. No pharmacological treatment was prescribed.

The client remained under psychiatric follow-up and during a review in early 2019 she was found to have developed delusions that she is pregnant, even though this was ruled out through physical investigation. Her speech was also noted to have deteriorated further, and she sounded more disjointed and incoherent than previously documented. Her mood was becoming more labile, with episodes of explosive laughter or crying. She was commenced on treatment with olanzapine due to her delusional beliefs.

This case is noteworthy because the client presented at a later age than expected in classical semantic dementia. Even though she was initially suspected of having memory problems, it subsequently became apparent that her difficulties are due to language impairments, highlighting the need of a careful cognitive examination even in patients of an older age group. The neuroimaging findings were typical of semantic dementia, and the predominance of left-sided atrophy correlates with the clinical picture of a predominantly verbal semantic deficit. The emergence of emotional lability, a sign of frontal lobe dysfunction, a few months later highlights how with fronto-temporal lobe dementias it is usual to develop overlapping symptoms as the neurodegenerative process spreads.

Case 3: Progressive non-fluent aphasia

A 78-year-old lady presented with progressive difficulty in word finding, slow and effortful speech and loss of her interests and energy. Her son felt that she was also finding it difficult to multi-task and was socially slightly withdrawn. There was also a suggestion that she may be depressed but her cognitive impairment seems more severe than expected of a mood disorder.

She scored 68/100 on ACE loosing points on verbal fluency and attention. Object naming was only slightly impaired. Short term memory was good but she did badly on visuospatial tasks. MRI scan of the brain showed prominent left perisylvian atrophy (Figure 3). 

FTD scan

 

 

3: Axial T2 slice shows that the atrophy is most marked in the left peri-sylvian region. This feature is suggestive of progressive non-fluent aphasia.

 

 

 

The diagnosis of progressive non-fluent aphasia was made but the differential includes “logopenic” variant of Alzheimer’s disease. A review by a speech and language therapist was arranged. The client was explained that gradually more difficulties such as social difficulties are likely to develop and speech would become progressively more difficult.

Discussion

The cases described in this article varied significantly in their age of onset of symptoms, and one was as young as 37 years when referred for a memory assessment. Even though the sixth decade is regarded as the age of peak incidence for frontotemporal dementia, epidemiological studied have identified a very wide range in age of onset.13

All cases, including the one diagnosed with behavioural-variant frontotemporal dementia, eventually developed severe language impairments. This highlights the degree of symptomatic overlap seen between clinical sub-types of frontotemporal dementia, a phenomenon already well described in the literature.1

A significant degree of mood disturbance was also seen in all cases, indicating that mood abnormalities are often co-morbid with frontotemporal dementia. The case of semantic dementia also developed a delusional disorder. The development of psychiatric symptoms in the early stages of frontotemporal dementia is well documented in the literature, and this often leads to a primary psychiatric diagnosis, commonly bipolar disorder, before the possibility of a dementing illness is considered.14

In all cases, a structural brain scan was enough to provide sufficient evidence to corroborate the clinical diagnosis. None of the cases were referred for PET or SPECT scans.

Finally, the progression of symptoms in all cases was steady and progressive, and this pattern is well recognised in the literature. The case of behavioural variant frontotemporal dementia deteriorated more rapidly than the two cases of language variant frontotemporal dementia. Prognosis of the different clinical sub-types of FTD is generally regarded in the literature to be comparable, except when there is the development of motor neurone disease which significantly worsens the prognosis.15  Although the described case of behavioural variant frontotemporal dementia was not formally diagnosed with motor neurone disease, he is currently immobile and has difficulty swallowing, suggesting that he may have developed some features of this disorder.


Dr Chris Barbara, Specialist Trainee in Old Age Psychiatry, Dr Ramona Rita Barbara, Specialist Trainee in Radiology and Dr Muhammad Rafiq, Consultant Neurologist, Norfolk and  Norwich University Hospital


References

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