Frontotemporal dementia

🧠 Pick’s Disease (a form of Frontotemporal Dementia, FTD) is a rare neurodegenerative disorder. Some cases show intracytoplasmic tau-positive inclusion bodies, making it a type of tauopathy (also seen in Alzheimer’s disease).

📖 About

• Rare dementia with frontal and anterior temporal lobe involvement.
• Onset usually age 50–70, mean ~58 years.
• Key features: behavioural changes, disinhibition, loss of empathy.

🧬 Aetiology

• Mutations in microtubule-binding protein tau.
• Right prefrontal/anterior temporal lobe → behavioural syndrome.
• Left prefrontal lobe → primary progressive aphasia.

🔬 Pathology

• Neuronal loss and gliosis.
• Spongiform degeneration in superficial cortical layers.
• Pick bodies – round tau-positive intracytoplasmic inclusions.
• Pick cells – large ballooned neurons in superficial cortex.

🔄 Variants

• Behavioural variant FTD – disinhibition, impulsivity, apathy.
• Primary Progressive Aphasia (PPA):
  • Non-fluent variant (agrammatism, effortful speech).
  • Fluent/semantic variant (loss of word meaning).
• Corticobasal degeneration: alien limb, apraxia, stiff jerky limb.
• FTD-MND overlap: FTD may precede motor neurone disease (usually men <65).

👩‍⚕️ Clinical Features

• Behavioural changes early: apathy, disinhibition, overeating, impulsivity.
• Personality change: inappropriate sexual behaviour, poor hygiene, loss of empathy.
• Cognitive decline: loss of executive functions, poor judgement, later memory loss.
• Speech/language: aphasia, dysarthria, loss of fluency.
• Neurological features: akinetic rigidity, limb apraxia, pseudobulbar palsy, spastic dysarthria.
• Advanced: vertical gaze palsy, alien hand syndrome, MND features.

🧪 Investigations

• Bloods: FBC, U&E, LFT, TFT, B12, folate, syphilis screen (exclude reversible causes).
• MRI: frontal and anterior temporal lobe atrophy (may be asymmetrical).
• SPECT/PET: reduced anterior perfusion.
• EEG: usually normal (helps distinguish from Alzheimer’s).
• EMG: if MND suspected.

💊 Management

• ❌ No disease-modifying treatment.
• ❌ Cholinesterase inhibitors / memantine not effective.
• ✅ SSRIs: can help compulsive behaviour, hyperorality, depression.
• ✅ Quetiapine: may be used for behavioural disturbance (short-term).
• ✅ Supportive: MDT care, OT, social services, caregiver support.
• Advance care planning early due to progressive decline.

🧠 Frontotemporal Dementia – Clinical Cases

• Case 1: Behavioural Variant FTD (bvFTD)
  A 58-year-old accountant is brought by his wife because of marked personality change over 18 months. He has become disinhibited, eating excessively, making inappropriate jokes, and neglecting work. There is no memory loss early on, but planning and empathy have deteriorated. Neurological examination is normal except for mild frontal release signs. MRI shows frontal and anterior temporal lobe atrophy; CSF Alzheimer biomarkers are negative.
  Teaching point: bvFTD is characterised by early behavioural disinhibition, apathy, and loss of executive control with preserved episodic memory initially. Misdiagnosis as a psychiatric disorder is common. SSRIs may help behavioural symptoms, but disease-modifying therapy is not yet available.


• Case 2: Primary Progressive Aphasia – Semantic Variant
  A 64-year-old retired teacher presents with a two-year history of progressive word-finding difficulty. She speaks fluently but uses vague terms (“that thing”, “the animal”) and fails to name common objects. Reading aloud is preserved, but comprehension of single words is impaired. Neuro exam is normal. MRI reveals asymmetric (left > right) anterior temporal lobe atrophy. Diagnosis: semantic-variant primary progressive aphasia, a form of FTD.
  Teaching point: Semantic-variant PPA causes loss of word meaning and object recognition, reflecting anterior temporal degeneration. Contrast with the non-fluent/agrammatic variant (effortful speech) and logopenic variant (word-retrieval pauses, usually Alzheimer-related).

💡 Clinical pearl: Think FTD in any patient < 65 years with progressive personality or language change but relatively preserved memory. MRI pattern of frontal ± temporal atrophy clinches the diagnosis. Genetic forms (MAPT, GRN, C9orf72) account for ~30–40% of cases.