Fronto-temporal (Pick's) Dementia

See related articles on Dementia.

This is a progressive dementia, first described by Arnold Pick in 1892, which typically affects the frontal and/or temporal lobes (unlike Alzheimer's disease and other dementias localised to posterior parietal lobes). This is now considered part of an overlapping collection of syndromes which are more common than has been thought in the past.¹ The term Pick Complex now incorporates other frontotemporal dementias. It is a common cause of dementia before age 65.²

Pick's disease is defined by severe atrophy, neuronal loss and gliosis with Pick cells (ballooned neurons) and Pick bodies (argentophilic neuronal inclusions) found disproportionately in the frontal and temporal cortical regions.^3,4

• Pick's disease is, after Alzheimer's disease and diffuse Lewy body disease, one of the most common cortical neurodegenerative dementias. It is the fourth commonest cause of dementia if vascular or non-neurodegenerative dementia is included.
• Clinically 10-15% of patients with dementia may have features suggesting Pick's disease, but only about a third of these meet neuropathological criteria specific for Pick's disease.
• In some series most patients with autopsy confirmed Pick's disease have been diagnosed in life as another neurodegenerative disease (usually Alzheimer's disease).⁵
• It may occur more frequently in Scandinavian countries. Familial forms linked to chromosome 17q are more common in people of Scandinavian origin where it makes up as much as 17% of dementias.
• More men than women may be affected.
• It affects a younger age group than Alzheimer's with peak incidence at age 55-65.⁶

Onset of behavioural and cognitive effects is insidious. In the first 2 years there are:

• Psychiatric problems following a frontal lobe pattern. This may produce aggression, socially inappropriate behaviour,stereotypical behaviour (orbitofrontal area). Lack of concern and apathy can occur (dorsomedial area).
• Depression may occur early on and often starts before amnesia.
• Speech and language problems develop early and deterioration is rapid. Memory problems are less severe than the behavioural and language difficulties early in the disease.
• Incontinence tends to develop early on unlike in Alzheimer's disease
• Parkinsonism may develop but not as prominently as in Lewy body disease.⁶

On examination:

• Patients are often very unkempt and may exhibit inappropriate jocularity ("Witzelsucht") or disinhibition.
• Patients may exhibit echolalia (repeating the examiners words) and echopraxia (copying the examiners gestures).
• Neurological examination may show primitive reflexes (grasp, sucking etc), akinesia with plastic rigidity. Resting tremor suggests parkinsonism.

Mental state examination may reveal:

• Nonfluency of verbal output and difficulty naming objects (anomia).
• Sparse, spontaneous and grammatically correct speech (logopenia).

Visuospatial and visual orientation skills are relatively well preserved.

Clinical diagnostic features of fronto-temporal dementia are listed in annex 6 of the latest sign guidance.⁷

Includes:

• Alzheimer's disease.
• Cerebrovascular disease.
• Conditions affecting the frontal lobes including frontal lobe epilepsy, frontal lobe syndromes, frontal and temporal lobe dementia, frontal lobe tumours, olfactory groove meningiomas etc.
• HIV related disease such as AIDS Dementia Complex.
• Huntington's Disease.
• Hydrocephalus.
• Herpes simplex encephalitis.
• Tertiary neurosyphilis.
• Sequential bilateral thalamic strokes.
• Lyme disease.
• Multiple sclerosis.
• Prion-related diseases.

• Blood for dementia screen (B12, TFTs, TPA, ANF) if encephalopathy suspected (FBC, LFTS, biochemistry, ammonia level, ESR and urine toxicology) if parkinsonism ceruloplasmin and serum copper (to exclude Wilson's disease) with a peripheral blood screen for acanthocytes.
• Genetic tests for Huntington's disease may be indicated.
• Further tests may include CSF examination (for chronic meningitis and HIV related disease) and if inattention is prominent exclusion of Lyme disease (Lyme serology) and metastatic carcinoma may be necessary.
• Brain biopsy in exceptional circumstances may be required (diagnosis in doubt, substantial benefit to patient or family from tissue diagnosis, treatment with adverse effects being considered (eg autoimmune therapy for neurosarcoidosis).

Imaging may be necessary:

• CT scan of the brain if MRI contraindicated.
• MRI is preferred as CT scans can miss relevant pathology, for example metastases and subcortical infarcts.
• Functional scans such as PET scans may be used to demonstrate acquired disease (for example for employment related concerns).

Lumbar puncture with extensive testing of CSF is done routinely by some specialists in the field.

This should incorporate:

• Stopping drugs which may be exacerbating memory problems or confusion (anticholinergics, CNS drugs).
• Treatment of symptoms of depression.
• Consider thiamine/ vitamins.
• Proceed with first and second line investigations as appropriate.
• Help with organisation of social and family care.
• Provide information to the family fully discussing investigations, results, diagnosis and management.

Referrals to other agencies will be required including geriatric medicine, psychiatry, psychology, social work and community nursing.⁸

Subdural haematoma is a greater risk after lumbar puncture in Pick's disease.⁶

Slow progression of symptoms with increased disability both at work and home is usual. Some patients develop creative and artistic interests. It runs a shorter course than Alzheimer's disease with a 6 year median survival after onset. Some forms where speech is predominantly affected may progress more slowly.⁹

Where there is a strong family history of frontotemporal dementia genetic testing should be discussed. Genetic counselling should be undertaken before testing is undertaken.