Key Facts

FTD is frequently misdiagnosed as psychiatric illness (especially bvFTD) due to prominent behavioural and personality changes with preserved memory. Early diagnosis is important for family support, genetic counselling, and future planning.

Epidemiology

Prevalence ~15-22 per 100,000 in 45-65 age group. Equal M:F. Mean age of onset 55-65 years (but range 40-75). Accounts for ~5% of all dementia but ~20% of young-onset dementia.

Aetiology

• Sporadic (~60%)
• Familial (~40%): C9orf72 hexanucleotide repeat expansion (commonest — also causes ALS), GRN (progranulin — haploinsufficiency), MAPT (tau mutations)
• Overlap with MND: ~15% of FTD patients develop MND; ~15% of MND patients develop FTD

Pathophysiology

Selective neurodegeneration of frontal and anterior temporal lobes. Two main protein aggregates: tau (FTLD-tau — Pick disease, PSP, CBD) and TDP-43 (FTLD-TDP — including C9orf72, GRN). Less common: FUS protein. bvFTD: orbitofrontal and anterior cingulate cortex → disinhibition, apathy. svPPA: anterior temporal lobe (left dominant) → loss of semantic knowledge. nfvPPA: left posterior frontal/insular cortex → effortful, agrammatic speech.

Behavioural Variant FTD (bvFTD — 60%)

• Disinhibition: socially inappropriate behaviour, loss of manners, impulsivity
• Apathy/inertia: loss of interest, reduced motivation (most common symptom)
• Loss of empathy/sympathy: cold, detached, disregarding others' feelings
• Compulsive/ritualistic behaviours: hoarding, rigid routines, clock-watching
• Dietary changes: sweet food craving, overeating, putting inedible objects in mouth
• Executive dysfunction: poor planning, but memory and visuospatial skills relatively preserved early

Semantic Variant PPA (svPPA)

• Progressive loss of word meaning (semantic memory)
• Fluent but 'empty' speech; word comprehension impaired
• Single-word naming difficulty
• Surface dyslexia/dysgraphia
• Left anterior temporal lobe atrophy ('knife-edge')

Non-Fluent Variant PPA (nfvPPA)

• Effortful, halting, agrammatic speech
• Speech sound errors (apraxia of speech)
• Comprehension of single words preserved (unlike svPPA)
• Left posterior frontal/insular atrophy

Red Flags

• Young-onset behavioural/personality change with preserved memory → FTD not AD
• FTD + motor neurone disease features → C9orf72 or MAPT
• Misdiagnosis as psychiatric disorder is common (especially bvFTD)

Imaging

• MRI brain: frontal and/or anterior temporal lobe atrophy (may be asymmetric); relatively preserved hippocampi (vs AD)
  • bvFTD: frontal (orbitofrontal, medial frontal) ± anterior temporal atrophy
  • svPPA: left anterior temporal lobe atrophy (knife-edge)
  • nfvPPA: left posterior frontal/insular atrophy
• FDG-PET: frontal/temporal hypometabolism (more sensitive than MRI early)

Cognitive Testing

• ACE-III: low fluency subscores; relatively preserved memory/visuospatial (early bvFTD)
• Formal neuropsychology: executive dysfunction, social cognition deficits

Bloods

• Exclude reversible causes: B12, TFTs, syphilis, HIV
• Serum progranulin level: screening for GRN mutations (low level)

Genetic Testing

• C9orf72, GRN, MAPT: offered if familial or MND overlap; genetic counselling essential

CSF

• AD biomarkers (Aβ42, tau): to exclude AD (normal in FTD)
• Neurofilament light chain (NfL): raised in FTD (non-specific marker of neurodegeneration)

Other

• EMG: if MND features suspected

Pharmacological

• No effective disease-modifying treatment
• ChEIs NOT effective in FTD (may worsen behavioural symptoms)
• SSRIs (sertraline, citalopram, fluoxetine): for disinhibition, compulsive behaviours, dietary changes, irritability — moderate evidence
• Trazodone 50-300mg: for agitation, aggression, sleep disturbance
• Antipsychotics: AVOID if possible (risk of EPS, poor evidence); low-dose risperidone or quetiapine only if severe aggression/risk

Non-Pharmacological

• MDT: neurology, psychiatry, SALT, OT, PT, neuropsychology, social work
• Structured routines, environmental modification
• Behavioural management strategies (carer education)
• SALT: communication strategies for PPA variants
• Nutrition: dietary management for overeating/sweet craving

Carer Support

• FTD is especially challenging for carers due to behavioural symptoms
• Alzheimer's Society, FTD-specific support groups (Rare Dementia Support)
• Respite care
• Safeguarding: may engage in risky/illegal behaviour (disinhibition)

Legal/Ethical

• Capacity assessment (may lack insight into own behaviour)
• Lasting power of attorney (arrange early while capacity retained)
• Driving: usually must cease early (DVLA notification)

Genetic Counselling

• Offered to all patients and at-risk family members

Referral Criteria

• Specialist memory/cognitive neurology service: all suspected FTD
• Genetics: if familial pattern or MND overlap
• Old age psychiatry: behavioural management

Mean survival from symptom onset: ~6-8 years (range 2-20). bvFTD: ~8 years. svPPA: ~12 years (slowest progression). nfvPPA: ~7 years. FTD-MND: worst prognosis (~3-5 years due to MND). Progression to severe disability: loss of speech (PPA), severe behavioural disturbance, dependence for all ADLs. Death usually from pneumonia, cachexia, or MND complications. No disease-modifying treatment available.

FTD Variants Comparison

FTD Genetics