Frontotemporal Dementia
Summary
Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders characterised by progressive atrophy of the frontal and temporal lobes. It is the second most common cause of dementia in those under 65 years. Unlike Alzheimer's disease, FTD typically presents with early changes in personality, behaviour, and language, with relative preservation of memory in early stages. There are three main clinical variants: behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA), and non-fluent variant PPA (nfvPPA). Underlying pathology involves abnormal accumulation of tau protein or TDP-43. There is no disease-modifying treatment; management is supportive. FTD may overlap with motor neurone disease (FTD-MND).
Key Facts
- Definition: Progressive dementia due to frontal and temporal lobe degeneration
- Age at Onset: Typically 45-65 years (early-onset dementia)
- Variants: Behavioural (bvFTD), Semantic PPA, Non-fluent PPA
- Pathology: Tau or TDP-43 protein inclusions
- Key Feature: Personality/behaviour change (bvFTD) or language problems (PPA)
- Memory: Often PRESERVED early (unlike Alzheimer's)
- Treatment: No disease-modifying therapy; SSRIs for behaviour
Clinical Pearls
"Personality Before Memory": In FTD, personality and behaviour change BEFORE memory loss. This is the opposite of Alzheimer's disease.
"Think FTD if Under 65": FTD is the most common cause of dementia in those under 65. Always consider it in younger patients with behavioural or language decline.
"Donepezil Doesn't Work": Unlike Alzheimer's, FTD is not primarily a cholinergic disorder. Acetylcholinesterase inhibitors are generally NOT effective.
"FTD-MND Overlap": 15% of FTD patients develop motor neurone disease features. Look for bulbar signs, weakness, and fasciculations.
Incidence
- 2-5 per 100,000 per year
- Second most common early-onset dementia (after Alzheimer's)
Demographics
- Peak onset: 55-65 years (range 21-80)
- Equal M:F (slight male predominance in bvFTD)
- 40% have positive family history
Genetics
- Autosomal dominant in 10-25%
- Key genes: MAPT (tau), GRN (progranulin), C9orf72 (hexanucleotide repeat)
- C9orf72 expansion also linked to ALS/MND
Neuropathology
- Selective atrophy of frontal and anterior temporal lobes
- Neuronal loss and gliosis
- Protein inclusions: Tau or TDP-43 (or FUS rarely)
Classification by Pathology
| Pathology | Protein | Subtypes |
|---|---|---|
| FTLD-Tau | Tau | Pick's disease, PSP, CBD |
| FTLD-TDP | TDP-43 | Types A-E |
| FTLD-FUS | FUS | Rare |
Why Behaviour/Language Affected?
- Frontal lobe: Executive function, personality, social behaviour
- Temporal lobe: Language, semantic memory
Clinical Variants
| Variant | Key Features |
|---|---|
| Behavioural (bvFTD) | Personality change, disinhibition, apathy, loss of empathy, hyperorality |
| Semantic Variant PPA | Loss of word and object meaning, fluent but empty speech |
| Non-fluent Variant PPA | Effortful, non-fluent speech, agrammatism |
Behavioural Variant FTD (bvFTD) - Most Common
Core Features:
Preserved Early:
Semantic Variant PPA
Non-Fluent Variant PPA
Mental State Examination
- Behaviour: Disinhibition, apathy, socially inappropriate
- Speech: Fluent but empty (svPPA) or non-fluent (nfvPPA)
- Affect: Blunted, reduced empathy
Cognition
- Memory: Relatively preserved early (vs Alzheimer's)
- Executive function: Impaired (frontal tests)
- Language: Depending on variant
Neurological Examination
- Primitive reflexes: Grasp reflex, palmomental reflex (frontal release signs)
- Motor signs: If FTD-MND overlap - weakness, wasting, fasciculations, bulbar signs
- Parkinsonism: May be present (overlap with PSP, CBD)
First-Line
| Test | Purpose |
|---|---|
| Cognitive testing | ACE-III, MMSE; pattern of deficits |
| Blood tests | Exclude reversible causes (B12, TSH, syphilis, HIV) |
| MRI Brain | Frontal and/or temporal atrophy (asymmetric) |
Imaging Findings
| Variant | MRI Atrophy Pattern |
|---|---|
| bvFTD | Frontal > temporal (often asymmetric) |
| svPPA | Anterior temporal (left > right) |
| nfvPPA | Left posterior frontal/insular |
Additional
- FDG-PET: Hypometabolism in frontal/temporal lobes
- Genetic testing: If family history (MAPT, GRN, C9orf72)
- CSF: May exclude Alzheimer's (normal amyloid/tau ratio in FTD)
General Principles
┌──────────────────────────────────────────────────────────┐
│ FRONTOTEMPORAL DEMENTIA - MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ NO DISEASE-MODIFYING TREATMENT │
│ │
│ SYMPTOMATIC MANAGEMENT: │
│ │
│ BEHAVIOURAL SYMPTOMS: │
│ • SSRIs (e.g., Sertraline, Citalopram) │
│ - For impulsivity, disinhibition, compulsive behaviours│
│ • Trazodone │
│ - For agitation, sleep disturbance │
│ • Avoid antipsychotics if possible (risk of worsening) │
│ │
│ COGNITIVE: │
│ • Acetylcholinesterase inhibitors NOT recommended │
│ (not a cholinergic disorder; may worsen behaviour) │
│ • Memantine - limited evidence │
│ │
│ SUPPORTIVE: │
│ • Speech and language therapy (PPA variants) │
│ • Occupational therapy │
│ • Carer support and education │
│ • Advance care planning (early in disease) │
│ • Social services / respite │
│ │
│ IF FTD-MND OVERLAP: │
│ • Multidisciplinary MND team involvement │
│ • Consider riluzole │
│ │
└──────────────────────────────────────────────────────────┘
Non-Pharmacological
- Structured routines
- Environmental modifications
- Carer education and support
- Behavioural strategies
Disease-Related
- Progressive cognitive and functional decline
- Loss of independence
- Behavioural challenges (aggression, disinhibition, wandering)
- Language loss
- Swallowing difficulties (late stage)
Associations
- FTD-MND (15%): Motor neurone disease features
- Parkinsonism (PSP, CBD overlap)
Impact on Carers
- High carer burden
- Behavioural changes particularly distressing
- Early loss of employment and driving
Natural History
- Median survival: 6-8 years from symptom onset
- Range: 2-20 years depending on variant and presence of MND
Prognostic Factors
| Better | Worse |
|---|---|
| PPA variants (often slower) | bvFTD |
| No MND features | FTD-MND (survival 2-3 years) |
| Preserved function at diagnosis | Severe behavioural symptoms |
End-of-Life
- Progressive decline to dependence
- Dysphagia, aspiration pneumonia
- Advance care planning essential
Key Guidelines
- NICE NG97: Dementia: Assessment, Management and Support
- International Consensus Criteria for bvFTD (Rascovsky et al., 2011)
Key Evidence
Diagnosis
- Rascovsky Criteria for bvFTD: High sensitivity and specificity
- MRI showing frontal/temporal atrophy supports diagnosis
Treatment
- SSRIs: Limited RCT evidence but widely used for behavioural symptoms
- AChE inhibitors: NOT recommended (no benefit; may worsen)
What is Frontotemporal Dementia?
Frontotemporal dementia (FTD) is a type of dementia that affects the front and sides of the brain (the frontal and temporal lobes). These parts of the brain control personality, behaviour, and language.
How is it Different from Alzheimer's?
In Alzheimer's disease, memory is usually the first thing affected. In FTD, it's often personality and behaviour that change first, or language abilities. Memory may remain quite good for several years.
What Are the Symptoms?
Depending on the type, a person with FTD may:
- Act inappropriately in social situations
- Lose interest in things they used to enjoy
- Become apathetic or withdrawn
- Develop food cravings (especially for sweet foods)
- Have difficulty finding words or understanding speech
- Speak less or with difficulty
Why Does it Happen?
The brain cells in the frontal and temporal lobes gradually die. This is caused by abnormal proteins building up inside the cells. In some families, it is inherited.
Is There a Treatment?
Unfortunately, there is no cure or treatment that can slow the disease down. Medicines can help manage some symptoms, especially mood and behaviour problems. Support from therapists, dementia services, and carer groups is very important.
Who Can Help?
- Neurologist or psychiatrist
- Memory clinic
- Speech and language therapist
- Dementia support services (e.g., Alzheimer's Society, AFTD)
Primary Guidelines
- NICE. Dementia: assessment, management and support (NG97). 2018, updated 2023. nice.org.uk/guidance/ng97
- Rascovsky K, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456-2477. PMID: 21810890
Key Studies
- Gorno-Tempini ML, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014. PMID: 21325651
- Rohrer JD, et al. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain. 2011;134(Pt 9):2565-2581. PMID: 21908872