Dementia Flashcards
1
Q
Give four main types of Dementia disorders
A
- Alzheimer’s disease
- Dementia with Lewy bodies
- Frontotemporal dementia
- Vascular dementia
2
Q
What are the two ways to look at the Neuropathlogically presentations of dementia
A
- Microscopically
- Intra neuronal inclusion bodies
- Extra neuronal changes (plaques)
- Macroscopically
- Generalised brain atrophy
- Region specific atrophy depending on dementia disorder
- Enlarged ventricles
3
Q
Give some microscopic causes of Dementia
A
- Misfolding of proteins
- Abnormal accumulation
- Neuroinflammatory environment
- Damaged neurons
- Cell death
- Damaged neurons
- Proteins involved:
- Amyloid
- Tau
- Synuclein
4
Q
What dementia disease is caused by Tau abnormalities?
A
- Alzheimer’s disease
- can also be caused by Amyloid abnormalities
- Frontotemporal dementia
5
Q
What is Tau?
A
- a highly soluble protein found mostly in the brain
- it is mostly present in axons
- it has 6 isoforms and disease process lead to hyperphosphorylated forms of the protein
Functions
- modulate the stability of axonal microtubules
- transport
6
Q
Abnormalities in Tau
A
Hyperphosphorylated forms of Tau
- Paired helical filaments (PHF)
- Neurofibrillary tangles (NFTs)
- PHFs –> NFTs –> Neurodegeneration
- Phosphorylation of tau is regulated by activated kinases
- Hyperphosphorylation of tau can result in the self-assembly of tangles of paired helical filaments (PHF).
7
Q
Explain Neurofibrillary tangles
A
Described by Alois Alzheimer: consist of paired 10-nanometer diameter filaments twisted around each other in a helical manner (paired helical filaments HF)
- Seen in neurons after staining
- Hematoxylin
- Eosin
- Bielschowsky
- Bodian
- Congo red
- Most commonly found in temporal lobe structures
- Hippocampus
- Amygdala
8
Q
Amyloid Precursor Protein (APP) in normal and diseased brains
A
- APP is a transmembrane glycoprotein which is broken down and eliminated in normal brain
- APP is split by enzymes ß-secretase then y-secretase.
- ß-amyloid is a peptide of 39–43 amino acids
- Most common isoforms are Aβ40 and Aβ42
- Aβ40 is more common of the two, but Aβ42 is the more fibrillogenic and is thus associated with disease states.
- Fragments accumulate to form plaques, the build-up of ß-amyloid plaques cause neuronal damage
9
Q
Frontotemporal Dementia (FTD)
A
- Tau pathology, Pick’s disease described by Arnold Pick 1892
- Pick bodies
- rounded, microscopic structures found within neurons
- Aggregates of tau
- Hirano bodies
- Neurons swell, taking on a “ballooned” appearance. Hence, called balloon cells.
- Plaques and tangles are not found in Pick’s disease.
- FTD is present in frontal and anterior temporal lobes.
10
Q
What are Synuclein abnormalities?
A
- Parkinson disease
- Dementia with Lewy bodies
- Fibrillary aggregates of alpha-synuclein protein
11
Q
What are Synuclein?
A
- Small, presynaptic neuronal proteins comprised of α-, β-, γ-synucleins of which only α-synuclein aggregates
- Proteins of 140 amino acids, that is expressed predominantly in neurons
- Found in neurons and glial cells
- Function as lipid vesicle binding, inhibition of phospholipase D2 and protein kinase C, dopamine uptake and as a chaperone have been ascribed to α-synuclein.
- Predominantly expressed in neocortex, hippocampus, substantia nigra and cerebellum.
- Can aggregate to form intracytoplasmic inclusions in neurons (Lewy bodies).
12
Q
What are Lewy bodies?
A
- Spherical, intranuclear, cytoplasmic eosinophilic inclusions
- Abnormally truncated and phosphorylated neurofilament proteins
- Contain:
- Alpha-synuclein
- Ubiquitin
- Associated enzymes.
13
Q
Vascular dementia
A
- Can result from ischemic or hemorrhagic brain damage.
- The three most common mechanisms causing disease
- Single, strategically placed infarcts
- multiple cortical infarcts
- subcortical small-vessel disease.
- Clinical deficits are determined by the size, location, and type of cerebral damage.
- Because of the variety of pathogenic mechanisms involved in vascular dementia, clinical manifestations can vary.
14
Q
What steps need to be taking to reach a diagnostic conclusion of a Dementia disease?
A
- History
- Examination
- Bloods/ECG
- Neuropsychological
- Behavioural/Activities of Daily Living
- Neuroimaging
15
Q
What examinations are done when Dementia is a differential diagnosis?
A
- General examination
- Neurological examination
- Mental State Examination
