Frontotemporal dementia

Definition

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterised by progressive atrophy of the frontal and/or temporal lobes of the brain, leading to changes in personality, behaviour, language, and executive function. Unlike Alzheimer’s disease, memory impairment is less prominent in the early stages, and onset tends to occur at a younger age (often 45–65 years).

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Epidemiology

• Accounts for ~10–20% of all dementias in people under 65 years

• Mean age of onset: 50–60 years (can occur from 20 to 80 years)

• Men and women affected equally overall, though certain subtypes have slight sex predominance

• Strong genetic component: ~30–50% have a positive family history

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Etiology and Genetics

FTD can be sporadic or familial. Familial cases are often linked to autosomal dominant mutations.

Genetic mutations associated with FTD:

• MAPT (microtubule-associated protein tau) – leads to abnormal tau protein accumulation

• GRN (progranulin gene) – causes reduced progranulin production, leading to neuronal degeneration

• C9orf72 hexanucleotide repeat expansion – also associated with amyotrophic lateral sclerosis (ALS)

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Pathophysiology

• Selective neuronal loss and gliosis in the frontal and temporal lobes

• Abnormal protein accumulation:

  • Tau-positive inclusions

  • TDP-43-positive inclusions

  • FUS-positive inclusions

• Affected areas depend on the clinical subtype (behavioural vs. language variants)

• Early involvement of brain regions regulating behaviour, social cognition, and language

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Clinical Variants

1. Behavioural Variant Frontotemporal Dementia (bvFTD) – most common

• Personality change

• Loss of empathy, social awareness, and inhibition

• Impulsive or socially inappropriate behaviour

• Apathy and reduced motivation

• Changes in eating habits (hyperphagia, preference for sweet foods)

• Impaired executive function (planning, decision-making)

2. Language Variants (Primary Progressive Aphasia, PPA)

• Semantic Variant (svPPA) – progressive loss of word meaning, impaired naming, and single-word comprehension

• Nonfluent/Agrammatic Variant (nfvPPA) – effortful, halting speech with grammar errors and speech apraxia; comprehension relatively preserved early

3. FTD with Motor Neuron Disease (FTD-MND)

• Combination of cognitive/behavioural symptoms with ALS-like motor weakness and fasciculations

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Symptoms Progression

• Early: personality change, language difficulty, behavioural disinhibition

• Middle: severe communication problems, compulsive behaviours, emotional blunting

• Late: global cognitive decline, physical disability, mutism, swallowing problems

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Diagnosis

Clinical Criteria – diagnosis requires progressive deterioration plus specific behavioural/language deficits and supportive neuroimaging findings.

Neuroimaging:

• MRI: atrophy of frontal and/or temporal lobes (often asymmetric)

• FDG-PET: hypometabolism in affected regions

Neuropsychological Testing:

• Executive function deficits

• Language testing abnormalities depending on subtype

Laboratory Tests:

• Rule out reversible causes of dementia (thyroid function, vitamin B12, syphilis serology, HIV)

Genetic Testing:

• Consider in early-onset disease or strong family history

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Differential Diagnosis

• Alzheimer’s disease (AD) – memory decline earlier and more severe in AD

• Psychiatric disorders (major depression, bipolar disorder)

• Vascular dementia

• Dementia with Lewy bodies

• Chronic traumatic encephalopathy

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Management

There is no cure for FTD, and treatment focuses on symptom control, functional support, and caregiver assistance.

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1. Non-pharmacological Management

• Speech and language therapy for PPA

• Occupational therapy for daily living adaptations

• Behavioural strategies to manage disinhibition, compulsions, and apathy

• Caregiver education on disease progression and behavioural management

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2. Pharmacological Management (Symptom-based)

For behavioural symptoms (disinhibition, impulsivity, agitation):

• Selective serotonin reuptake inhibitors (SSRIs) – may reduce compulsive behaviour, overeating, disinhibition

  • Sertraline 50–200 mg orally once daily

  • Fluoxetine 20–60 mg orally once daily

  • Citalopram 10–40 mg orally once daily

For severe behavioural disturbance or agitation (if SSRIs insufficient):

• Atypical antipsychotics (use with caution due to side effects)

  • Quetiapine 12.5–25 mg orally twice daily, titrate as needed

  • Olanzapine 2.5–10 mg orally once daily

For depression or anxiety:

• SSRIs or venlafaxine (37.5–225 mg daily)

For motor symptoms in FTD-MND:

• ALS-specific interventions (riluzole 50 mg orally twice daily)

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3. Supportive Care

• Nutritional management (monitor for overeating and weight gain)

• Fall prevention strategies

• Swallowing assessment (speech therapy) to prevent aspiration

• Social work involvement for care planning and financial/legal issues

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Prognosis

• Gradual progression over 6–8 years from onset (range 2–20 years)

• Death often due to complications such as aspiration pneumonia, infections, or advanced immobility

• Earlier onset generally linked to faster decline

• Familial forms may have predictable patterns based on mutation type