11 - Frontotemporal dementia

Question 1

What is the most common age range for frontotemporal dementia?

Answer 1

→ between 45 - 64 (60%)
→ can get it as early as 21, and as late as 80, but these are less likely
→ because FTD can develop much earlier than alzheimers, it can have a bigger impact on your life

Question 2

What brain regions are involved in FTD? And what types of cognitive functions?

Answer 2

→ frontal and temporal lobes; behaviour, movement, language and emotion

Question 3

True or false: Symptoms of FTD are the same throughout all people.

Answer 3

False: varies between people; changes in personality and behaviour, difficulty moving, etc.
→ depends on the area that is affected, which determines what symptoms people will have

Question 4

Behavioural variant-FTD causes problems in what?

Answer 4

→ changes in personality, behaviour and judgment, problems doing tasks with multiple steps and become frustrated, act inappropriately or become disinterested

Question 5

What is PPA?

Answer 5

→ primary progressive aphasia; frontotemporal disorder that makes it difficult to use language
→ may lose their ability to speak, read, write or understand what others are saying

Question 6

What causes FTD?

Answer 6

• abnormal amounts of tau and TDP-43 proteins inside nerve cells in brain
  → tau protein in frontotemporal dementia is not the same as tau protein in the dementia we’ve seen – this is why the 2 disorders aren’t confused
• most cases, the cause is unknown, but changes in genes are an influence

Question 7

FTD is a group of disorders characterized by… (in terms of the brain)

Answer 7

FTD is a group of disorders characterized by progressive loss of cells in the frontal and temporal lobes

Question 8

FTD causes deterioration in…

Answer 8

deterioration in behavior, personality and/or difficulty producing or comprehending language

Question 9

True or false: FTD is a leading type of early-onset dementia.

Answer 9

True

Question 10

Why is diagnosis of FTD difficult?

Answer 10

• Diagnosis is difficult due to similarity in behavioral changes between FTD and psychiatric disorders
  → behavioural changes are often the first thing doctors or people close might look at
  → symptoms typically depend on which part of the brain is affected
  → p.ex: FTD can be clearly visible in someone when noticing changes in personality, in others it could be movement, and in others it could be language
  → those with changes in personality may have inappropriate behavior
  → is often misdiagnosed as alzheimers, depression or parkinsons because a lot of the symptoms overlap between all three of them (in behaviour)
  → it takes about 3.6 years typically to get an accurate diagnosis of FTD

Question 11

Generally speaking, what is FTD?

Answer 11

• FTD (aka frontotemporal lobar degeneration) is in fact a group of disorders, including a behavioral variant, progressive language impairment, or, rarely, movement disorders
• The frontal and temporal lobes shrink with symptoms varying depending on the area affected
  → frontal: personality, behaviour, judgment, impulse control and motor functions
  → temporal: memory, language and speech
• 1/3rd of cases are associated with genetics but there are no known risk factors for FTD
  → increased risk of getting it
  → theory rn that FTD is inherited, but with the people who are diagnosed with FTD, no one else developed it

Question 12

True or false: There are specific treatments for FTD.

Answer 12

False: No treatments exist, although medications can reduce behavioral symptoms

Question 13

What are the primary symptoms affected in FTD progression?

Answer 13

• Primary symptoms are often speech and movement
  → there are a lot of other diseases that impact these 2, so doctors will often jump to those first and look at it in that specific sense
  → but if it gets worse, that’s when the doctor will send for an MRI

Question 14

How does FTD typically progress in symptoms?

Answer 14

• Continually progresses, however, rate of decline varies between people
  → at earlier stages, people might just have 1 symptom, but as the disease progresses, other symptoms appear as more parts of the brain become affected; at this point it becomes more difficult to manage and control it
• People often show progressive muscle weakness and coordination problems
  → need of wheelchair, getting to a point where unable to leave beds
  → can cause problems; swallowing, chewing, controlling bladder
  → eventually die because of the physical changes that causes their skin and urinary tracts to decline and for lung infections to occur

Question 15

What is the average life expectancy of someone with FTD after the start of symptoms?

Answer 15

Average life expectancy is 7-13 years after the start of symptoms
- predisposed to physical illnesses (pneumonia, infections…) and injuries because of changes to their physical and movement
- but because FTD is so variable, it’s difficult to guess the timeline
→ this is an important note for this disease, it’s very variable between people, which makes it different to nail down
- if you go in early though and get a diagnosis, they can predict a timeline and help life expectancy to be longer (better lifestyle); if lifestyle is bad, life expectancy diminishes
→ the earlier you know, the earlier you can make changes to lifestyle that’ll help you live longer

Question 16

What are the risk factors of FTD?

Answer 16

• The only known risk factor for FTD is family history
• At least 8 genes - including some with very rare mutations
  → are known to cause FTD
• The behavioral variant of FTD is most often inherited; semantic FTD is only rarely inherited
• combo of genetic and environmental factors impact the risk of the disease; multifactorial inheritance
• 60-70% of the genetics of FTD are sporadic, 20-25% are familial, and 10-15% are inherited
• autosomal dominant inheritance

Question 17

What are the causes of FTD?

Answer 17

• Loss of neurons and abnormal amounts of proteins called tau and TDP-43
  → this is what makes it a conclusive diagnosis of FTD
• Tau: protein that is normally present and stabilizes neurons
  → although they look different, they function in a similar sense
  → Forms tangles inside neurons and leads to destruction of brain cells
  → tangles disrupt normal cell function and lead to the death of the neurons, particularly in the frontal and temporal lobes
• TDP-43: involved with gene expression and RNA/DNA processing and metabolism
  → Become mislocated from nucleus to cytoplasm and forms inclusions interfering with cell functions
  → affects the language and behavioural changes

Question 18

What is the behavioural variant FTD? what is it characterized by?

Answer 18

• The most common variant of FTD and includes changes in personality, behavior, and judgment
  Characterized by:
• Lack of motivation
• Disinterested in activities / people
• Disinhibition (apathy) / impulsivity
  → need extra prompts to initiate or even continue basic activities
  → socially inappropriate behaviour; act impulsively without considering how other people may feel
  → might even take part of criminal activities
  → make embarrassing personal remarks
• Problems planning
  → difficulty prioritizing what needs to be done first

Question 19

What happens in the brain with BV-FTD?

Answer 19

• Typical changes include atrophy of frontal lobes and anterior temporal (although temporal tends to be a to a lesser degree)
• Degree can be asymmetric (typically worse on right)
• progression in time
• progressive atrophy and cell loss in the frontal and specifically the anterior temporal regions of the brain which affects complex thinking, personality and behaviours
• Problems with cognition may present but memory stays intact
• Over time language and or movement problems may occur

Question 20

What is language variant FTD? (primary progression aphasia or PPA)

Answer 20

• Changes in ability to communicate (speak, read, write, and understand)
  → difficulties using and understanding words; difficulties speaking properly (slurred speech); may become mute or even unable to speak on top of the symptoms
• Language dysfunction is the main symptom for the first 2 years of the illness
  → many develop symptoms of dementia: problems with memory, reasoning and judgment; might not be evident at first, but can develop over time
• Deficits include language production, object naming, syntax, or word comprehension

Question 21

PPA or language variant FTD takes 2 forms, what are they?

Answer 21

1) Non-fluent PPA - speaking is hesitant, labored, or ungrammatical
2) Semantic variant – lose ability to understand or formulate words; recognize familiar faces or objects

Question 22

What are brain changes seen in non-fluent PPA?

Answer 22

• Atrophy is more variable (not consistent), typically in posterior frontal, and temporal lobe
• Generally left hemisphere is thought to be most affected but not universal
• this is where the broca’s area is (language central in the brain)

Question 23

What are brain changes seen in semantic variant PPA?

Answer 23

• Left hemisphere (anterior) temporal lobe atrophy
  → More anterior than posterior
  → Includes many areas including, amygdala, hippocampus, fusiform gyrus
• frontal atrophy is not a notable feature here, at least not in the early form of the disease
• decline in the corpus callosum
• dysgraphia: unclear, irregular or inconsistent handwriting (becomes more slanted)
  → also writing things down more slowly

Question 24

About __ in __ people with FTD will also develop a motor neuron disease.

Answer 24

1 in 10

Question 25

What are the 3 main movement/muscle function disorders in both types of FTD?

Answer 25

1) Amyotrophic lateral sclerosis (ALS): muscle weakness/wasting
2) Corticobasal syndrome: arms and legs become uncoordinated and/or stiff
3) Palsy (PSP): muscle stiffness, difficulty walking, changes in posture, with changes in eye movements also observed

Question 26

What is Amyotrophic lateral sclerosis (ALS): muscle weakness/wasting?

Answer 26

• One of the 3 main movement/muscle function disorders in FTD
  → These changes are the same observed in people with ALS
  → Muscle weakness and atrophy
  → Muscle jerks / wiggling in muscles
  → Difficulty grasping a pen or cup
  → Difficulty lifting arms above the head
  → Clumsiness when completing find motor movements with hands or fingers

Question 27

What is Corticobasal syndrome: arms and legs become uncoordinated and/or stiff?

Answer 27

• One of the 3 main movement/muscle function disorders in FTD
  → Most common symptom is apraxia – inability to use hands or arms to perform movements
  → Muscle rigidity and difficulty swallowing are also common
  → Symptoms often appear on one side of the body then progress to the other side
  → Can develop the motor symptoms after language difficulties and orientation objects in space
  → Not everyone with corticobasal syndrome has problems with memory, cognition, language, or behavior

Question 28

What is Palsy (PSP): muscle stiffness, difficulty walking, changes in posture, with changes in eye movements also observed?

Answer 28

• One of the 3 main movement/muscle function disorders in FTD
  → resembles what we see in parkinson; tremor is less common and language and speech symptoms tend to develop earlier
  → Typically move more slowly
  → Experience unexplained falls
  → Lose facial expression
  → Body stiffness observed particularly in the next and upper body
  → Eye movement tend to involved difficulty looking down

Question 29

What is the diagnostic criteria of FTD?

Answer 29

• Insidious onset
• Gradual progression
• Exclusion criteria:
  → Deficits better explained by other medical disorders
  → Deficits better explained by a psychiatric disorder
  → Biomarkers strongly suggest other neurodegenerative process

Question 30

What is the diagnostic criteria of behavioural variant FTD?

Answer 30

At least three:
- Behavioural disinhibition
- Apathy or inertia
- Loss of sympathy or empathy
- Stereotypical, compulsive, or perseverative behaviour
- Hyperorality or dietary changes
- Executive deficits with relative sparing of visuospatial skills and memory

Question 31

What is the diagnostic criteria of language variant PPA?

Answer 31

• Prominent language impairment
• Language deficits impair daily functioning
• Aphasia is the most prominent initial-phase deficit
  Exclusion criteria:
• Prominent early deficits in episodic memory, visual memory, or visuoperceptual skills
• Prominent early behaviour disturbances

Question 32

What is the diagnostic criteria of semantic variant PPA?

Answer 32

• Impaired confrontation naming
• Impaired single-word comprehension
  At least three:
• Impaired object knowledge
• Surface dyslexia or dysgraphia
• Spared repetition
• Spared speech production

Question 33

Rank BV-FTD, SV-PPA, NFV-PPA in terms of their frequency of social symptoms.

Answer 33

1. BV-FTD
2. SV-PPA
3. NFV-PPA

Question 34

Rank BV-FTD, SV-PPA, NFV-PPA in terms of their frequency of emotional symptoms.

Answer 34

1. SV-PPA
2. BV-FTD
3. NFV-PPA

Question 35

Rank BV-FTD, SV-PPA, NFV-PPA in terms of their frequency of eating and oral behaviours.

Answer 35

1. BV-FTD
2. SV-PPA
3. NFV-PPA

Question 36

Rank BV-FTD, SV-PPA, NFV-PPA in terms of their frequency of repetitive/compulsive and sensory symptoms.

Answer 36

1. BV-FTD
2. SV-PPA
3. NFV-PPA

Question 37

Rank BV-FTD, SV-PPA, NFV-PPA in terms of their frequency of language symptoms.

Answer 37

1. NFV-PPA
2. SV-PPA
3. BV-FTD

Question 38

Rank BV-FTD, SV-PPA, NFV-PPA in terms of their frequency of neuropsychiatric/other symptoms.

Answer 38

1. SV-PPA
2. BV-FTD
3. NFV-PPA