Frontotemporal Dementia

Question 1

Frontotemporal dementia

Answer 1

Frontotemporal dementia is a neurodegenerative disorder characterised by focal degeneration of the frontal & temporal lobes.

Question 2

Frontotemporal dementia (FTD) is a type of dementia that is characterised by predominant disturbances in …

Answer 2

Frontotemporal dementia (FTD) is a type of dementia that is characterised by predominant disturbances in social behaviour, personality and language (e.g. aphasia). This is accompanied by preferential degeneration of frontal and temporal lobes.

Question 3

FTD is a heterogeneous condition with various subtypes. It is an uncommon cause of dementia, but typically affects patients at …

Answer 3

FTD is a heterogeneous condition with various subtypes. It is an uncommon cause of dementia, but typically affects patients at a younger age (< 65 years). =

Question 4

Dementia describes a clinical syndrome that is characterised by a significant deterioration in mental function that leads impairment of normal function.

In healthcare, we measure ‘normal function’ by activities of daily living (ADLs). These are a series of routine activities that people should be able to do without assistance. They can be broadly divided into personal tasks and domestic tasks.

Answer 4

Personal: washing, dressing, toileting, continence, transferring (e.g. bed to chair)
Domestic: cooking, cleaning, shopping, managing finances, taking medication

Question 5

Early onset dementia is usually

Answer 5

FTD

FTD is overall uncommon compared to other forms of dementia. It is more commonly seen in patients with early onset dementia with a similar frequency to AD. The mean age of onset is 58 years old. The onset before 40 years old and after 75 years old is uncommon.

The sex prevalence is generally equal with some reporting a slight male predominance.

Question 6

Pick disease is an old clinical term that now refers to a pathological finding of Pick bodies, which contain tau protein inclusions. These may be seen in certain subtypes of FTD.

Answer 6

Pick disease is an old clinical term that now refers to a pathological finding of Pick bodies, which contain tau protein inclusions. These may be seen in certain subtypes of FTD.

Question 7

FTD is an umbrella term that refers to three clinical disease subtypes:

Answer 7

Behavioural variant (bvFTD): most common. Occurs in 50%. Characterised by progressive personality and behaviour change.
Primary progressive aphasia (PPA): characterised by insidious onset of progressive language defects (e.g. word finding, aphasia). There are two different types of PPA.
Non-fluent PPA: characterised by articulatory difficulty
Semantic PPA: characterised by impaired single-word comprehension

Question 8

FTD Aetiology

Answer 8

The exact cause of FTD is unknown, but is characterised by tissue deposition of aggregated proteins including phosphorylated tau or transactive response DNA-binding protein 43 (TDP-43). Tau is the major protein of ‘Pick bodies’ that may be seen in certain pathological subtypes. Tau is seen in other neurodegenerative diseases including motor neuron disease (MND) and corticobasal syndrome (CBS).

Question 9

Commonly implicated genes include (FTD)

Answer 9

Microtubule associated protein tau (MAPT): found on chromosome 17. Multiple identified mutations. Leads to a propensity of tau to form neurotoxic aggregates.
Granulin precursor (GRN): found on chromosome 17. Multiple identified mutations. Role in FTD is unclear.
C9ORF72 gene: found on chromosome 9. Most common genetic cause of inherited FTD. Also implicated in hereditary motor neuron disease. Usually results in bvFTD with or without MND.

Question 10

Pathophysiology - FTD

Answer 10

FTD is characterised by degeneration of frontal and/or temporal lobes.

Question 11

The pathological subtypes of FTLD include:

Answer 11

FTLD-Tau: characterised by hyperphosphorylated tau protein inclusions
FTLD-TDP: characterised by inclusions of abnormal phosphorylated and ubiquitinated TDP-43 proteins. Differentiated into subtypes A-D.
FTLD-ALS/DPR
FTLD-FUS

Question 12

The behavioural variant of FTD is most commonly seen (~ 50%). It is characterised by progressive change to personality and behaviour.

Typical features:

Answer 12

Disinhibition (e.g. socially inappropriate behaviour)
Loss of empathy
Apathy (losing interest and/or motivation)
Hyperorality (e.g. dietary changes, attempt to consume non-edible products, eat beyond satiety)
Compulsive behaviour (e.g. cleaning, checking, hoarding)

Question 13

PPA subtypes are less common and characterised by insidious changes to language. In the early stages of the disease, defects in language are typically isolated. The presentation varies depending on the subtype.

Typical language features:

Answer 13

Effortful speech
Halting speech
Speech-sound errors
Speech apraxia (i.e. difficulty in articulation)
Word-finding difficulty
Surface dyslexia or dysgraphia: mispronouncing difficult words (e.g. yacht)

Question 14

FTD with motor neuron disease: diagnosis of MND may precede or follow diagnosis of FTD. Behavioural and cognitive features consistent with bvFTD seen in 15-20% of the amyotrophic lateral sclerosis subtype. Causes upper and lower motor neuron symptoms (e.g. spasticity, weakness, atrophy, fasciculations).

Answer 14

FTD with motor neuron disease: diagnosis of MND may precede or follow diagnosis of FTD. Behavioural and cognitive features consistent with bvFTD seen in 15-20% of the amyotrophic lateral sclerosis subtype. Causes upper and lower motor neuron symptoms (e.g. spasticity, weakness, atrophy, fasciculations).

Question 15

… syndrome: a rare neurodegenerative disorder with significant overlap with FTD. Characterised by abnormal tau deposition (i.e. taupathy). Usually begins with cognitive or behavioural disturbance with development of characteristic motor features. Classical motor features include asymmetrical akinesia, dystonia, ideomotor apraxia or alien-limb phenomenon.

Answer 15

Corticobasal syndrome: a rare neurodegenerative disorder with significant overlap with FTD. Characterised by abnormal tau deposition (i.e. taupathy). Usually begins with cognitive or behavioural disturbance with development of characteristic motor features. Classical motor features include asymmetrical akinesia, dystonia, ideomotor apraxia or alien-limb phenomenon.

Question 16

Progressive … palsy: a rare neurogenerative disorder characterised by supranuclear gaze palsy (i.e. difficulty looking up). Clinical features cross over with FTD (cognitive and behavioural) and parkinson’s (bradykinesia, rigidity).

Answer 16

Progressive supranuclear palsy: a rare neurogenerative disorder characterised by supranuclear gaze palsy (i.e. difficulty looking up). Clinical features cross over with FTD (cognitive and behavioural) and parkinson’s (bradykinesia, rigidity).
Progressive supranuclear palsy: a rare neurogenerative disorder characterised by supranuclear gaze palsy (i.e. difficulty looking up). Clinical features cross over with FTD (cognitive and behavioural) and parkinson’s (bradykinesia, rigidity).

Question 17

Cognitive domains: FTD

Answer 17

Attention and concentration
Recent and remote memory
Language
Praxis: planned motor movement (e.g. perform a task)
Executive function
Visuospatial function

Question 18

Clinical assessment

FTD

Answer 18

Essential to determine characteristic clinical features. Patients may have poor insight so interviewing family members is important, especially for altered behaviour and personality. Cognitive tests are completed as part of the assessment.

The presence of typical features (e.g. abnormal social behaviour, eating disorder, stereotyped behaviour, apathy) in the absence of significant memory impairment is very specific to bvFTD. In the PPA subtype, it is characterised by progressive language defects with relative sparing of other cognitive domains during the early disease course.

Question 19

Imaging of the brain with MRI is useful to exclude an alternative diagnosis and to look at the pattern of involvement (e.g. frontal and/or temporal atrophy). Whilst imaging is supportive, it cannot be used solely to determine the diagnosis.

Typical features on neuroimaging:

Answer 19

bvFTD: frontal and temporal atrophy in up to 65%. Particularly anterior insula, anterior cingulate cortex, and amygdala. May be asymmetrical.
Nonfluent PPA: early atrophy and hypoperfusion in the left posterior fronto-insular cortex.
Semantic PPA: significant anterior temporal atrophy. Often asymmetric.

Question 20

Diagnostic criteria of FTD

Answer 20

There are different diagnostic criteria for each clinical subtype of FTD.

Diagnosis of bvFTD is based on the International Behavioral Variant FTD Criteria Consortium (FTDC) that uses clinical features, neuroimaging, neuropathology and genetic testing. Diagnosis of PPA is based on clinical criteria developed in 2011. These include clinical, neuroimaging and biomarker data to help diagnosis PPA and then determine the subtype.

Question 21

Management of FTD

Answer 21

There are no specific treatments for FTD and management is aimed at improving activities of daily living.

Question 22

Non-pharmacological interventions - FTD

Answer 22

Financial advice: particularly important due to behaviour and personality changes leading to impaired judgement. May need simple financial supervision initially but often a lasting power of attorney for finances once they lose capacity.
Physical supervision: particularly if behaviour is problematic
Exercise: regular exercise and cardiovascular fitness encouraged
Mobility: assessment by a physiotherapy and providing aids (e.g. walking stick, frame) as needed. May require occupational therapy assessment with adaptation of home environment
Speech and language: assessment by a speech and language therapist is important with communication aids and swallow assessment in later stages of disease
Behavioural modification: variety of methods effective, keeping a behaviour chart can be useful and ensuring carers get respite.

Question 23

What advice is particularly important in FTD?

Answer 23

Financial advice: particularly important due to behaviour and personality changes leading to impaired judgement. May need simple financial supervision initially but often a lasting power of attorney for finances once they lose capacity.

Question 24

FTD

Pharmacological treatments may be needed to help with behaviour and cognitive dysfunction. It is important to recognise these help control symptoms and are not disease modifying.

Usually need a specialist in old age psychiatry or neurology to initiate because medications can also exaggerate symptoms, cause motor symptoms and lead to deterioration in cognition.

Example options:

Answer 24

Serotonin reuptake inhibitors (SSRI): used for difficult behavioural symptoms. Have been shown to decrease disinhibition, anxiety, impulsivity and repetitive behaviours.
Atypical anti-psychotics: can help with agitation and behavioural symptoms. Due to side-effect profile, should be trialled after SSRIs.

Question 25

FTD Overall survival is …-… years from symptoms onset.

Answer 25

Overall survival is 8-10 years from symptoms onset.

Question 26

Prognosis - FTD

Answer 26

Survival is often shorter in patents with bvFTD compared to PPA. Patients usually have increasing dependancy for activities of daily living requiring carers and eventually permanent nursing home residence if care needs cannot be met in their own home.

It is critical that family and close friends are involved in the patients care to help with care needs, treatment decisions and appropriate advanced care planning.