AP: Neurodegeneration and Dementia

Question 1

What are the common features shared by Neurodegenerative Diseases?

Answer 1

• Progressive
• Fatal
• Associated with ageing
• Degeneration of neurons (dysfunction and cell death)

Many:

• abnormal accumulation of proteins in CNS

Question 2

What are common pathological factors?

Answer 2

• Commonest in old age
• Each disease affects specific neuronal groups
• Atrophy of affected areas (on imaging or macroscopically)
• Regional pattern of atrophy may give clue to diagnosis

Question 3

Explaint the different neuropathological classifications by protein accumulation

Answer 3

• beta amyloid - Alzheimer’s disease
• Tau - 3R and 4R - Alzheimer’s disease
• α-synuclein - Parkinson’s disease
• TDP-43 - FTLD-TDP
• polyglutamine repeat expansions - Huntington’s, spinal cerebellar ataxia

Question 4

Most NDDs prsent in either of which 2 ways

Answer 4

1. Specific neurological syndromes - e.g. loss of motor neurones -> muscle weakness in MND
2. Dementia - due to widespread neuronal dysfunction or cell death e.g. AD, LBD

Question 5

What is dementia?

Answer 5

An acquired progressive global impairment of intellect, memory and personality, without impairment of consciousness.

Excludes:

• acute confusional state
• impairment of consciousness
• delirium or depression
• mental impairment due to maldevelopment or brain trauma

Question 6

What proportion of dementia is caused by Alzheimer disease? Lewy body Dementia? Frontotemporal lobal degeneration? Vascular pathology?

Answer 6

AD - 70%

FTD - 10%

LBD - 10%

Vascular pathology - 10%

Question 7

What are the histopathological features of Alzheimer’s disease?

Answer 7

• Amyloid B-protein accumulation - neuritic plaques and cerebral amyloid angiopathy
• Tau accumulation - neurofibrillary tangles
• Loss of neurones and synapses

Question 8

What is the difference between Parkinson’s disease and parkinsonism?

Answer 8

Parkinson’s disease is a disease (either sporadic or hereditary)

Parkisonism is a symptom (problem with adrenergic pathways) that occurs in many conditions (toxic parkinsonism, drug-induce, vascular parkinsonism)

Question 9

What are the clinical features of PD?

Answer 9

• Mask-like faces
• Bradykinesia
• Rigidity
• Festinant gait (foot shuffle)
• Pill-rolling tremor

Question 10

What is the second most common dementia?

Answer 10

Dementia with Lewy Bodies - 10-25% cases

Question 11

What are the different cassifications of human prion diseases (spongiform encephalopathies)?

Answer 11

1. Creutzfeld-Jakob disorder

• sporadic
• iatrogenic - didn’t clean equipment properly
• familial - germline mutation
• variant - oral ingestion of BSE contaminated meat

2. Gerstmann-Strussler-Scheinker disease
3. Fatal familial insomnia
4. Kuru
   * oral or parenteral transmission from kuru-infected human tissue (ritualistic cannibalism)

Question 12

What is prion disease?

Answer 12

PrP is a normal cellular transmembrane protein of uncertain function.

Prion disease is due to an abnormally folded form of the protein, which has a tendency to aggregate and cause spongiform change.