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Neurology > Dementia Pathology > Flashcards

Dementia Pathology Flashcards

1
Q

Where do dementias typically affect?

A

Anatomically and functionally related groups of neurons

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2
Q

Define dementia

A

Acquired and persistent generalised disturbance of higher mental functions in an otherwise fully alert person - always pathological

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3
Q

What are the two classifications of dementia?

A

Primary

Secondary

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4
Q

Name primary dementias

A
  • Alzheimer’s
  • Lewy body dementia
  • Pick’s disease (fronto-temporal)
  • Huntington’s
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5
Q

Name secondary dementias

A
  • Vascular dementia
  • Infection (HIV)
  • Trauma
  • Drugs/alcohol
  • Metabolic
  • SOL/increased ICP
  • Paraneoplastic syndrome
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6
Q

What is the most common type of dementia?

A

Alzheimers

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7
Q

When does Alzheimer’s usually present?

A

After 60 years old - the later the onset the more severe the disease

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8
Q

What percentage of alzheimers are familial?

A

1%

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9
Q

What syndrome increases your risk of alzheimer’s?

A

Down’s

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10
Q

State the symptoms at each stage of Alzheimers

A
  • insidious impairment of higher intellectual function with alterations in mood and behaviour
  • marked disorientation, memory loss and aphasia (cortical dysfunction)
  • profound disability mutness and immobility
  • death due to secondary cause (pneumonia)
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11
Q

Describe the macroscopic brain changes seen in Alzheimers

A

Decreased brain size and weight
Widening of sulci, thinning of gyri
Ventricular dilatation
Occipital, brainstem and cerebellum preservation

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12
Q

What can compensatory ventricular dilatation lead to?

A

Secondary hydrocephalus

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13
Q

Describe the microscopic features of alzheimers

A
  • Loss of neurons, astrocyte proliferation
  • Neurofibrillary tangles
  • Tau protein abnormality
  • Neuritic plaques
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14
Q

What are neurofibrillary tangles?

A

Bundles of insoluble microtubules in the cytoplasm of neurons

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15
Q

What are neuritic plaques?

A

A beta amyloid plaques, they are focal spherical collections of dilated tortuous processes of neurons that surround a central amyloid core with astrocytes and microglia

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16
Q

Describe the pathology of alzheimers

A

Instead of producing alpha secretase APP produces beta and gamma secretases

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17
Q

What does A beta do?

A
  • Oligomerises and froms amyloid fibrils
  • Promote hyperphosphorylation and mislocalisation of TAU to the cell body
  • Indirectly activates NMDA receptors post synpatically
    Overall leading to excitotoxicity
18
Q

How does amyloid angiopathy occur?

A

Abeta oligomerises and accumulates within the wall of arterioles causing thickening and stiffening compromising the BBB

19
Q

What is the effect of amyloid angiopathy?

A

Local oedema, hypoxia, exaccerbating exotoxicity and further neuronal injury, vessels are prone to rupture causing intracerebral haemorrhage

20
Q

What stain is used to identify amyloid angiopathy?

A

Congo red

21
Q

What is Lewy Body dementia?

A

Progressive disease with hallucinations and fluctuating levels of attention and cognition

22
Q

What is often the first symptom of Lewy body dementia?

A

REM sleep behaviour disorder - lack of sleep paralysis and acting out of dreams

23
Q

What is Lewy body dementia associated with?

A

Motor symptoms of Parkinsons

24
Q

What are the pathological features of Lewy body dementia?

A

Degeneration of the substantia nigra, pale due to loss of pigmented dopaminergic neurons, neuronal atrophy and gliosis

25
Q

Define Lewy body

A

Single/multiple intracytoplasmic eosinophilic round to elongated bodies that have a dense core and surrounding pale halo

26
Q

What protein can be found in lewy bodies?

A

Alpha synuclein

27
Q

When does Huntington’s usually present?

A

35-50 years old

28
Q

What are the clinical features of huntington’s?

A
  • emotional
  • cognitive
  • hyperkinetic motor
29
Q

What are the symptoms of huntington’s?

A

Chorea, myoclonus, clumsiness, slurred speech, depression, irritability and apathy
Later onset dementia

30
Q

What is the genetic issue in huntington’s?

A

Trinucleotide repeat disease

31
Q

What is the macroscopic appearance of huntington’s?

A

Atrophy of basal ganglia particularly caudate nucleus and putamen
Later - frontal, parietal and cortical atrophy
Compensatory expansion of third ventricles

32
Q

Describe the microscopic appearance of Huntington’s

A

Degeneration of stiratal neurons, most severely in caudate nucleus, loss of inhibitory regulation of motor activity, pronounced astrocytic gliosis

33
Q

What is another name for fronto-temporal dementia?

A

Pick’s Disease

34
Q

When does pick’s disease usually present?

A

50-60 years old

35
Q

What are the symptoms of pick’s disease?

A

Personality and behavioural change (frontal)
Speech and communication problems (temporal)
Changes to eating habits
Reduced attention span

36
Q

What is the mean length of survival in pick’s?

A

2-10 years mean in 7 years

37
Q

Describe the pathology seen in Pick’s disease

A

Extreme atrophy of the frontal and temporal lobes with sparing of parietal and occipital, brain weighs less than 1kg with marked neuronal loss most severe in outer 3 layers of the cortex

38
Q

What are Pick’s bodies?

A

Intracytoplasmic filamentous inclusions enriched in TAU

39
Q

What is multi-infarct dementia?

A

Disorder involving deterioration in mental functioning due to cumulative damage to the brain through hypoxia or anoxia (lack of oxygen) as a result of multiple blood clots

40
Q

What volume loss leads to dementia?

A

50-100mls

41
Q

What are the risk factors for multi-infarct dementia?

A

Hypertension

Stroke

42
Q

How does multi-infarct dementia progress?

A

Abrupt onset

Stepwise deterioration

Neurology (29 decks)

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