Rare and Unusual Dementias

Dementia Aware: what you need to know about other types of dementia

Dementia is a common and growing problem worldwide. Whilst ninety-five per cent of cases are attributable to Alzheimer’s disease, vascular dementia, Lewy body dementia etc., little is known about the remaining five per cent of dementia cases. These types of dementia are extensive, and are known as rare and unusual dementias.

In 2002, a European Union project on rarer forms of dementia estimated a prevalence of five cases per 10,000 people in the community (Alzheimer’s Europe 2002-2003).

Rare and unusual dementias are classified into four groups:

1. Degenerative Causes: Familial Alzheimer’s disease, progressive supranuclear palsy
2. Vascular Causes: CADASIL, normal pressure hydrocephalus
3. Infectious Causes: neurosyphilis, HIV and AIDS dementia complex
4. Human Prion Disease: fatal familial insomnia, Creutzfeldt-Jakob disease

Degenerative Causes of Dementia

Progressive Supranuclear Palsy:

• Also called Steele-Richardson-Olszewsky syndrome
• Occurs around age 60 years
• Characterised by tauopathy (abnormal levels of tau protein) with nigral (eye movement, motor skills) and corticobasal (movement) degeneration which involves the cerebral cortex (outer layer of neural tissue of the cerebrum), plays a key role in memory, awareness, thought, language, attention and perception
• Classic symptoms: supranuclear gaze palsy (inability to look in a direction based on area of brain affected), backwards arching and rigidity of neck with gait problems and imbalance (tend to fall backwards)
• Cognitive symptoms: reduced verbal fluency, inattention and executive dysfunction (planning, abstract thinking, behavioural control)
• Disease progression is slow with initial retention of insight

Vascular Causes of Dementia

Normal Pressure Hydrocephalus:

• Pathophysiology is unclear but there is a possible cerebrovascular role
• Easily mistaken for Alzheimer’s disease or Parkinson’s disease
• A build up of CSF (cerebrospinal fluid) in the brain ventricles (hollow fluid filled chambers)

caused by an obstruction or absorption is impeded

• Can be secondary to other conditions e.g. brain hemorrhage, meningitis
• Alzheimer like symptoms occur because the enlarged brain ventricles press on and damage nearby brain structures that affect memory, walking and bladder control
• Signs and symptoms known as the classic triad: “wet, wacky, wobbly”

1. urinary urgency, frequency and incontinence
2. cognitive impairment, confusion, prominent memory loss, slowness of thought
3. gait disturbance (like walking on a boat), weakness, short, shuffling, wide steps

• Diagnosis: CT Scan/MRI of head, presence of the classic triad, thorough case history
• Treatment: CSF drained by lumbar puncture and/or drain CSF from brain by a shunt
• Prognosis: if effective, gait will improve almost immediately, and the milder the dementia, the more likely it will improve. However, for those with moderate to advanced dementia, there is unlikely to be a significant improvement

Infectious Causes of Dementia

Syphilis is a sexually transmitted disease caused by a bacterial infection. It is treated with Penicillin. Syphilis has been increasing since the advent of the HIV epidemic. Since 1996, rates of syphilis have increased significantly amongst homosexual men and men and women 55 years and older.

Neurosyphilis:

• Neurosyphilis develops in 25 to 40 per cent of untreated people (Mehrabian, et al., 2009)
• Usually presents more than 10 to 25 years after initial infection
• It is a slow, progressive destructive infection of the brain and spinal cord
• Changes in personality, cognition, mood, severe executive dysfunction, can present as a frontal lobe type dementia
• Psychiatric symptoms include mania, grandiose delusions, paranoia
• Neurological signs include ataxia (poor coordination), disturbed speech, abnormal pupils, nerve pain, pain in extremities, seizures, paralysis
• Diagnosis: blood tests – rapid plasma regain (RPR)
• Treatment: IV Penicillin
• Prognosis: symptoms may be ‘potentially reversed’ if person responds to treatment

Human Prion Disease

A prion is an infectious particle. When it enters the body, the prion begins folding into an abnormal almost 3D shape and triggers the existing normal forms of protein to change into the prion shape. In the brain, the prion protein affects the grey matter with subsequent nerve loss, gliosis (scarring) and characteristic spongiform change (small round empty spaces) There are four types of human prion disease that cause dementia:

Sporadic Creutzfeldt-Jakob disease:

• Most common form (85 per cent)
• Occurs after age 50 years
• Early signs: headaches, weight gain, fatigue and depression
• Then rapidly progressing global dementia, myoclonus, ataxia, progressive pyramidal, extrapyramidal and cerebellar dysfunctions with gait, vision (leading to blindness) and speech problems
• Diagnosis: EEG (electroencephalograph) CSF analysis, MRI, tonsil biopsy is negative
• Medications may be given to reduce the severity of movement disorders and for comfort measures
• Prognosis: rapidly progressing disease where the person can neither move nor speak (akinetic mutism), death follows in six months to one year

Iatrogenic Creutzfeldt-Jakob disease:

• Caused by inadvertent transmission of CJD between humans mostly via medical procedures e.g. corneal graft, prion infected surgical instruments
• Symptoms, investigations, treatment as per sporadic CJD, progresses very rapidly

Variant Creutzfeldt-Jakob disease:

• Also known as mad cow disease
• Caused by transmission of prion protein variants via food originating from cattle e.g. beef
• Psychiatric symptoms: depression, personality changes, irritability, aggression, fleeting delusion
• Neurological deficits: chorea, ataxia, myoclonus, dysaesthesias and dementia
• Diagnostic tests: MRI, tonsil biopsy for prion protein is positive
• Life expectancy usually 12 to 14 months

Familial Creutzfeldt-Jakob disease:

• Also called human spongiform encephalopathy
• Accounts for 10 to 15 per cent of all CJD cases
• Age at onset can be as early as age 20, but more common ages 40 to 50 years
• Symptoms and treatment as per sporadic CJD
• As this if familial, genetic testing may identify carriers and early/late onset varieties of this disease, therefore genetic counselling is essential