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Pathology (Guide) > Histopathology - Neurodegenerative Diseases > Flashcards

Histopathology - Neurodegenerative Diseases Flashcards

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1
Q

What are neurodegenerative diseases?

A

Progressive, irreversible conditions leading to neuronal loss

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2
Q

What is the common pathogenic mechanism for neurodegenerative disease?

A

Accumulation of misfolded proteins which may be intra- or extracellular

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3
Q

What is dementia?

A
  • A global impairment of cognitive function + personality withouth impairment of consciousness.
  • Impairment goes beyond what mught be expected from normal ageing.
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4
Q

What are the components of dementia?

A
  • Memory impairment + atleast one cognitive disturbance:
  • Aphasia
  • Apraxia
  • Agnosia
  • Disturbance in executive functioning
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5
Q

What is aphasia?

A

Language disorder

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6
Q

What is apraxia?

A

Loss of ability to carry out learned purposeful tasks

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7
Q

What is anomia?

A

The loss of ability to recall/find words

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8
Q

What is agnosia?

A

Loss of ability to recognise objects, people etc.

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9
Q

What are the 5A’s associated with dementia?

A
  • Amnesia
  • Apraxia
  • Aphasia
  • Agnosia
  • Anomia
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10
Q

What are the most to least common types of dementia?

A
  • Alzheimers
  • Vascular
  • Lewy body
  • Fronto-temporal
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11
Q

What is the onset of Alzheimer’s disease?

A

> 50yrs

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12
Q

How is Alzheimer’s diagnosed?

A

Clinically
- PET/MRI may help

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13
Q

What is the pathophysiology of Alzheimer’s disease?

A
  • Accumulation of β-amyloid deposits outside nerines
  • Leads to senile plaques that interfere with neuronal communication
  • Hyperphosphorylation of Tau protein
  • Leads to dissociation from neurine microfilaments and accumulation into neurofibrillary tangles
  • Causes cerebral atrophy
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14
Q

What are the radiological findings of Alzheimer’s disease?

A
  • General brain atrophy
  • Widened sulci
  • Narrowed gyri + enlarged ventricles: medial temporal lobes + hippocampus = loss of cholinergic neurones
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15
Q

What is seen on histology for Alzheimer’s disease?

A
  • Senile plaques of β-amyloid protein
  • Neurofibrillary tangles of tau protein
  • Cerebral amyloid angiopathy
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16
Q

What is the staging system used for Alzheimer’s?

A

BRAAK Staging

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17
Q

What is the treatment for Alzheimer’s Disease?

A

Symptomatic:
- Anti-cholinesterases
- nAChR agonists
- Glutamate antagonists

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18
Q

What is the pathophysiology of Vascular dementia?

A
  • Neuronal death due to infarcts of small + medium sized vessels
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19
Q

What are the symptoms of Vascular dementia?

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A
  • Step-wise deterioration
  • Sx reflect area of brain affected
20
Q

What are some RFs for Vascular dementia?

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A
  • Atherosclerosis
  • Obesity
  • Smoking
  • Alcohol
  • Diabetes
  • Unhealthy diet
  • Sedentary lifestyle
21
Q

What are the symptoms of Lewy body dementia?

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A
  • Psychological disturbances occur early
  • Day-to-day fluctuations in cognitive performance + alterness
  • Visual hallucinations (little people/animals running around)
  • Spontaneous motor signs of Parkinsonism
  • Recurrent falls + syncope
  • Aggression
22
Q

What is the pathology of Lew body dementia?

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A

Pathologically indistinguishable from Parkinson’s

23
Q

What areas of the brain are affected in fronto-temporal dementia?

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A
  • Only frontal + temporal lobes (Atrophy)
24
Q

What is seen on histology of fronto-temporal dementia?

Study These Flashcards
A

Pick bodies
- Hyperphosphorylated tau

25
What mutations are associated with Lewy body dementia?
Progranulin gene
26
What is the onset of Lewy body dementia?
- Strong FHx - Younger people (40-60yrs)
27
What are some symptoms associated with Lewy body dementia?
- Personality change - Disinhibition - Overeating - Emotional blunting
28
What is Parkinson's disease?
Progressive depletion of dopaminergic neurones in the nigrostriatal pathway from substantia nigra in basal ganglia to striatum - Leads to widespread motor deficits
29
What is the pathophysiology of Parkinson's disease?
- Lewy bodies present in affected neurones - Α-synuclein is main component of Lewy bodies - Mutations in Α-synuclein cause Parkinson's
30
Where are Α-synuclein deposits found?
- Lewy bodies (in neurones) - Peripheral ganglia (motor retardation) - Olfactory bulb (Early loss of smell)
31
What are the cardinal signs of Parkinson's?
TRAP - T: Tremor - R: Rigidity - A: Akinesia - P: Postural instability + Psychiatric features in later disease: - Dementia - Hallucinations - Anxiety
32
What are some Parkinson Plus Syndromes?
- Lewy body dementia - Progressive supranuclear palsy - Corticobasal syndrome - Multiple system atrophy - Vascular parkinsonism - Drug-induced
33
What is Progressive Supranuclear Palsy and its features?
Tauopathy with limited vertical gaze (downgaze) - Early falls - Axial rigidity - Akinesia - Dysarthria - Dysphagia
34
What is Corticobasal Syndrome and its features?
Tauopathy with varied presentation - Unilateral parkinsonism - Dystonia/myoclonus - Apraxia +/- ALIEN LIMBS phenomenon - ?Progressive non-fluent aphasia
35
What is Mutliple System Atrophy and its features?
Synucleinopathy - Early autonomic dysfunction - Cerebellar predominant (MSA-C) - Parkinsonism predominant (MSA-P)
36
What are some features of Drug-induced Parkinsonism?
Bilateral Sx
37
What misfolded pathological proteins are associated with Alzheimer's disease?
- Tau - Β-amyloid
38
What misfolded pathological proteins are associated with Lewy body Dementia?
- Α-synuclein - Ubiquitin
39
What misfolded pathological protein is associated with Corticobasal degeneration?
Tau
40
What misfolded pathological protein is associated with Frontotemporal dementia (linked ot Chr 17)?
Tau
41
What misfolded pathological protein is associated with Pick's disease?
Tau
42
What is Prion Disease?
A series of diseases with common molecular pathology often caused by infection + transfer of proteins from organism to host (rather than RNA/DNA)
43
What are the different types of Prion Diseases and their incidences?
Sporadic (80%): - Creutzfeld-Jakob disease Acquired (<5%): - Kuru - Variant CJD - Iatrogenic CJD Genetic (15%): - Gerstmann-Straussler-Scheinkler Syndrome (GSS) - Fatal Familial Insomnia
44
What is a feature of Creutzfeld-Jakob disease?
Rapid <1yr decline
45
What is a feature of Kuru Disease?
Cannibalism
46
What is a feature of Variant CJD?
Linked ot bovine spongiform encephalopathy (e.g. mad cow disease)
47
What is a feature of Iatrogenic CJD?
Following flood transfusions of surgical procedures

Pathology (Guide) (84 decks)

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