Dementia Pathology Flashcards
(42 cards)
Where do dementias typically affect?
Anatomically and functionally related groups of neurons
Define dementia
Acquired and persistent generalised disturbance of higher mental functions in an otherwise fully alert person - always pathological
What are the two classifications of dementia?
Primary
Secondary
Name primary dementias
- Alzheimer’s
- Lewy body dementia
- Pick’s disease (fronto-temporal)
- Huntington’s
Name secondary dementias
- Vascular dementia
- Infection (HIV)
- Trauma
- Drugs/alcohol
- Metabolic
- SOL/increased ICP
- Paraneoplastic syndrome
What is the most common type of dementia?
Alzheimers
When does Alzheimer’s usually present?
After 60 years old - the later the onset the more severe the disease
What percentage of alzheimers are familial?
1%
What syndrome increases your risk of alzheimer’s?
Down’s
State the symptoms at each stage of Alzheimers
- 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)
Describe the macroscopic brain changes seen in Alzheimers
Decreased brain size and weight
Widening of sulci, thinning of gyri
Ventricular dilatation
Occipital, brainstem and cerebellum preservation
What can compensatory ventricular dilatation lead to?
Secondary hydrocephalus
Describe the microscopic features of alzheimers
- Loss of neurons, astrocyte proliferation
- Neurofibrillary tangles
- Tau protein abnormality
- Neuritic plaques
What are neurofibrillary tangles?
Bundles of insoluble microtubules in the cytoplasm of neurons
What are neuritic plaques?
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
Describe the pathology of alzheimers
Instead of producing alpha secretase APP produces beta and gamma secretases
What does A beta do?
- 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
How does amyloid angiopathy occur?
Abeta oligomerises and accumulates within the wall of arterioles causing thickening and stiffening compromising the BBB
What is the effect of amyloid angiopathy?
Local oedema, hypoxia, exaccerbating exotoxicity and further neuronal injury, vessels are prone to rupture causing intracerebral haemorrhage
What stain is used to identify amyloid angiopathy?
Congo red
What is Lewy Body dementia?
Progressive disease with hallucinations and fluctuating levels of attention and cognition
What is often the first symptom of Lewy body dementia?
REM sleep behaviour disorder - lack of sleep paralysis and acting out of dreams
What is Lewy body dementia associated with?
Motor symptoms of Parkinsons
What are the pathological features of Lewy body dementia?
Degeneration of the substantia nigra, pale due to loss of pigmented dopaminergic neurons, neuronal atrophy and gliosis
