Frontotemporal Dementia (FTD)

Last edited on April 30, 2020

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Frontotemporal dementia (FTD), also known as lobar degeneration (FTLD), or less commonly, Pick's disease, is the most common causes of dementia in adults younger than 60 years. It is characterized by uninhibited behavior, hyperorality, lack of empathy, impaired executive function, and lack of sympathy. Loss of insight is one of the core features of the frontal/behavioural variant frontotemporal dementia (FTD).

Prevalence

Approximately 2-10 per 100,000 people. Approximately 20%-25% of cases of frontotemporal NCD occur in individuals older than 65 years. Frontotemporal NCD accounts for approximately 5% of all cases of dementia. The behavioral variants and semantic language variant are higher in males, and and nonfluent language variant are higher among females.

Disease Course

The disease is gradually progressive, with a median survival of 5-10 years after symptom onset and 4 years after diagnosis.

Frontotemporal dementia can be classified into four clinical variants:^[1]

Behavioral (or frontal) Variant (BV-FTD) - there is relative preservation of recall, and behaviour is usually the first change
Semantic Variant Primary Progressive Aphasia (SV-PPA)
Logopenic Variant
Non-fluent (agrammatic) Variant Primary Progressive Aphasia (NFV-PPA) - patients are often stumbling for words, and grammar is very poor

See main article: ppa

ALS (Amyotrophic Lateral Sclerosis) and FTD have a considerable clinical and pathological overlap. A pathogenic hexanucleotide repeat expansion within the C9ORF72 gene is thought to be a major cause of both disorders.^[2] Indeed, a proportion of patients with FTD also develop ALS.^[3]

Individuals with behavioral-variant frontotemporal dementia may present with apathy or disinhibition. Patients typically lose interest in socialization, self care, and personal responsibilities, or display socially inappropriate behaviours, such as sexual disinhibition. Insight is usually impaired as well. Cognitive impairment is much less prominent during the early stages, and few deficits are found on cognitive testing.

Criterion A

The criteria are met for major or mild neurocognitive disorder.

Criterion B

The disturbance has insidious onset and gradual progression.

Criterion C

Either (1) or (2);

Behavioural variant
- a. 3 or more of the following behavioural symptoms:
  - Behavioural disinhibition
  - Apathy or inertia
  - Loss of sympathy or empathy
  - Perseverative, stereotyped or compulsive/ritualistic behaviour
  - Hyperorality and dietary changes
- b. Prominent decline in social cognition and/or executive abilities
Language variant
- a. Prominent decline in language ability, in the form of speech production, word finding, object naming, grammar, or word comprehension.

Criterion D

Relative sparing of learning and memory and perceptual-motor function.

Criterion E

The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Probable frontotemporal neurocognitive disorder is diagnosed if either of the following is present; otherwise, possible frontotemporal neurocognitive disorder should be diagnosed:

Evidence of a causative frontotemporal neurocognitive disorder genetic mutation, from either family history or genetic testing.
Evidence of disproportionate frontal and/or temporal lobe involvement from neuroimaging.

Possible frontotemporal neurocognitive disorder is diagnosed if there is no evidence of a genetic mutation, and neuroimaging has not been performed.

Genetic mutations associated with FTD include the encoding of microtubule-associated protein tau (MAPT) and granulin (GRN), C90RF72,^[4] transactive response DNA-binding protein of 43 kDa (TDP-43, or TARDBP), valosin-containing protein (VCP), chromatin modifying protein 2B (CHMP2B), and fused in sarcoma protein (PUS). The majority of FTD cases remain sporadic.

A CT head or MRI head can show patterns of atrophy of the frontal lobes that can aid in the clinical diagnosis. Neuroimaging is also helpful to exclude other differential diagnoses such as mass lesions and hydrocephalus.

Neuroimaging Findings

Variant	Neuroimaging Findings
Behavioral variant	Both frontal lobes (in particular the medial frontal lobes) and anterior temporal lobes have atrophy
Semantic variant	Middle, inferior, and anterior temporal lobes are atrophic bilaterally but asymmetrically, with the left side usually being more affected
Logopenic variant	Associated with predominantly left posterior perisylvian or parietal atrophy
Nonfluent variant	Associated with predominantly left posterior frontal-insular atrophy

The Frontal Assessment Battery (FAB) is commonly used as a screening test. The Montreal Cognitive Assessment (MoCA) can also be used to screen for early mild cognitive changes. Since the Mini-Mental Status Exam (MMSE) does not include an assessment for impaired executive function, it may not detect changes indicative of FTD.

Alzheimer's Disease (AD) - about 10%-30% of patients presenting symptoms suggestive of FTD are found at autopsy to have Alzheimer's disease pathology.
progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) - FTD overlaps with on brain pathology
Creutzfeldt-Jakob Disease (CJD) - usually has a much more progressive onset, compared to FTD, which is slowly progressive

There are no approved treatments for FTD. All current treatments are thus off-label and used to manage symptoms of the disease.^[5] In fact, the evidence suggests cholinesterase inhibitors may exacerbate behavioural symptoms. Antidepressants as a class have been shown to lead to some behavioural improvement.^[6]

Behavioural Symptoms

For behavioural symptoms, SSRIs may be effective, including: citalopram, fluoxetine, and sertraline. Trazodone similarly has evidence for the treatment of behavioural symptoms related to FTD^[7] Antipsychotics and anti-epileptics have also been shown to be effective in the management of behavioural symptoms, but are limited in use due to their side effect profile. Like with managing all forms of behavioural symptoms of dementia it is very important to rule out potential triggers for behavioural disturbances such as infections, electrolyte changes, medical issues, and environmental stressors prior to initiating psychotropic medications.