Frontotemporal Dementia and Primary Progressive Aphasia

What Frontotemporal Dementia is

Frontotemporal Dementia (FTD) is a group of neurodegenerative disorders that selectively affect the frontal and temporal lobes of the brain. The pathology underlying FTD is heterogeneous and includes tau-related, TDP-43 related, and FUS-related conditions. Genetic mutations account for a substantial minority of cases, particularly in those with a strong family history.

FTD is the second most common dementia of working age. Onset is most commonly in the fifth or sixth decade, although later-onset cases are increasingly recognised.

The three main syndromes

Behavioural Variant Frontotemporal Dementia

Behavioural Variant Frontotemporal Dementia is characterised by a relatively gradual change in personality, social conduct and judgment, with relatively preserved memory in the early stages. Six core diagnostic features (the Rascovsky 2011 criteria) are:

• Early behavioural disinhibition (impulsive, socially inappropriate behaviour);
• Early apathy or inertia;
• Early loss of sympathy or empathy;
• Perseverative, stereotyped or compulsive behaviours;
• Hyperorality and dietary changes (sweet preference, overeating, unusual food choices);
• Executive dysfunction with relative sparing of memory and visuospatial skills.

Primary Progressive Aphasia (PPA)

Primary Progressive Aphasia is dominated by progressive language difficulty. Three variants are recognised (Gorno-Tempini 2011 criteria):

• Non-fluent Variant Primary Progressive Aphasia, with effortful, halting speech, agrammatism and apraxia of speech;
• Semantic Variant Primary Progressive Aphasia, with loss of word meaning, single-word comprehension difficulty and naming impairment, alongside fluent but empty speech;
• Logopenic Variant Primary Progressive Aphasia, with word-finding pauses, impaired repetition of sentences and phonological errors. Logopenic PPA is often an atypical Alzheimer's Disease presentation rather than a Frontotemporal pathology.

Frontotemporal Dementia with Motor Neuron Disease

A subset of Frontotemporal Dementia cases develop features of Motor Neuron Disease (Amyotrophic Lateral Sclerosis), with muscle wasting, weakness and fasciculation. Around 15 to 20 per cent of Behavioural Variant Frontotemporal Dementia cases have, or will develop, Motor Neuron Disease features. This combination has a more rapid course.

Movement-predominant variants

Progressive Supranuclear Palsy and Corticobasal Syndrome are Frontotemporal-spectrum disorders with prominent motor features, including falls, abnormal eye movements, rigidity, and asymmetric limb apraxia.

How it is diagnosed

The diagnostic process emphasises history (often from a close family member, who frequently notices the change earlier than the person themselves), cognitive testing, structural and where needed functional imaging, and genetic testing when appropriate.

• Addenbrooke's Cognitive Examination (ACE-III) with attention to verbal fluency (often markedly reduced) and the language and behavioural domains;
• A structural Magnetic Resonance Imaging brain scan, looking for asymmetric or lobar (frontal or temporal) atrophy. Magnetic Resonance Imaging may be normal in early disease;
• FDG-PET or perfusion SPECT when structural Magnetic Resonance Imaging is non-contributory. NICE NG97 1.2.23 supports their use;
• Genetic testing where there is a clear family history or young-onset features.

How it is treated

There is no licensed medication that slows or reverses Frontotemporal Dementia. Treatment is symptomatic, supportive, and centred on the family.

Behavioural symptoms

Non-pharmacological approaches are first line: routine, structured environment, removing triggers, redirecting rather than confronting, and engagement in meaningful activity. Where pharmacological treatment is needed, Selective Serotonin Reuptake Inhibitors (SSRIs) such as Sertraline or Citalopram may reduce disinhibition, compulsive behaviour and overeating. Antipsychotic medicines should be used cautiously and only when necessary.

Language symptoms

Speech and Language Therapy is the mainstay of support for Primary Progressive Aphasia. Therapy is tailored to the variant and includes word-retrieval strategies, communication aids, and family training.

Motor symptoms

Physiotherapy, occupational therapy and, in some cases, neurology input for Parkinsonian features.

Cholinesterase Inhibitors

Cholinesterase Inhibitors are not recommended for Frontotemporal Dementia. They may worsen behavioural symptoms.

Genetic considerations

Around 10 to 30 per cent of Frontotemporal Dementia cases have a strong family history. The commonest disease genes are C9orf72 (which can also cause Motor Neuron Disease), GRN (progranulin), and MAPT (microtubule-associated protein tau). Genetic counselling and, where appropriate, testing should be considered when there is a strong family history. Predictive testing in asymptomatic relatives is a complex decision and should be made with specialist input.

What course it takes

Mean life expectancy from diagnosis is around 7 to 10 years for Behavioural Variant Frontotemporal Dementia, and somewhat longer for Semantic Variant Primary Progressive Aphasia. The course is shorter, often 3 to 4 years, when Motor Neuron Disease develops alongside.

Where to get assessed

Frontotemporal Dementia and Primary Progressive Aphasia are commonly under-recognised in general memory clinics. If you suspect Frontotemporal Dementia in yourself or a family member, particularly with behavioural change without major memory loss or with a predominantly language-led decline, a specialist memory assessment is valuable. The Dementia Service is the leading UK Private Memory Clinic and can arrange MRI, FDG-PET and genetic onward referral where indicated.