Dementia Pathology Flashcards
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
Define Lewy body
Single/multiple intracytoplasmic eosinophilic round to elongated bodies that have a dense core and surrounding pale halo
What protein can be found in lewy bodies?
Alpha synuclein
When does Huntington’s usually present?
35-50 years old
What are the clinical features of huntington’s?
- emotional
- cognitive
- hyperkinetic motor
What are the symptoms of huntington’s?
Chorea, myoclonus, clumsiness, slurred speech, depression, irritability and apathy
Later onset dementia
What is the genetic issue in huntington’s?
Trinucleotide repeat disease
What is the macroscopic appearance of huntington’s?
Atrophy of basal ganglia particularly caudate nucleus and putamen
Later - frontal, parietal and cortical atrophy
Compensatory expansion of third ventricles
Describe the microscopic appearance of Huntington’s
Degeneration of stiratal neurons, most severely in caudate nucleus, loss of inhibitory regulation of motor activity, pronounced astrocytic gliosis
What is another name for fronto-temporal dementia?
Pick’s Disease
When does pick’s disease usually present?
50-60 years old
What are the symptoms of pick’s disease?
Personality and behavioural change (frontal)
Speech and communication problems (temporal)
Changes to eating habits
Reduced attention span
What is the mean length of survival in pick’s?
2-10 years mean in 7 years
Describe the pathology seen in Pick’s disease
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
What are Pick’s bodies?
Intracytoplasmic filamentous inclusions enriched in TAU
What is multi-infarct dementia?
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
What volume loss leads to dementia?
50-100mls
What are the risk factors for multi-infarct dementia?
Hypertension
Stroke
How does multi-infarct dementia progress?
Abrupt onset
Stepwise deterioration
