Neurodegeneration & cognitive disorders Flashcards
(37 cards)
What is a neurodegenerative disorder?
Give three examples
A progressive CNS disease (but not all progressive diseases are NDD)
e.g. Alzheimer’s, Parkinson’s, Dementia with Lewy bodies, MND
What do the following conditions have in common?
- Batten’s
- Niemann-Pick
- Tay-Sachs
- very rare
- recessive
- result: mutant protein
- occur in childhood
What do the following conditions have in common?
- Huntington’s
- Myotonic dystrophy
- fairly rare
- dominant (repeats)
- results: mutant protein
- any age
What do the following conditions have in common?
- Alzheimer’s
- Parkinsons
- MLD
- common
- polygenic
- result: misfolded protein
- middle age onset
Which protein goes wrong in the following diseases?
- Alzheimer’s
- Parkinsons
- MLD
Alzheimers: tau (+ amyloid)
Parkinsons: aSyn
MLD: TDP-43
What happens before neurones die in NDD?
Give an example of this pathognomonic finding
Before neurones die the proteins within them aggregate forming what is known as an inclusion body
- these can be seen on microscopy
e.g. neurofibrillary tangles in Alzheimers
What happens in rapid neuronal loss?
Give an example of a condition where this happens?
Spongiosis: fluid-filled holes
e.g. in CJD, FTLD
Outline the central dogma of NDD
Native protein becomes misfolded
(this is usually corrected by chaperone proteins, but this failed in NDD, protein degradation also occurs)
Misfolded protein undergoes oligomerization which results in oligers, protofibrils and other intermediates
(these can damage the cells and cause a loss of function as less native protein)
These undergo fibril formation –> fibrils
The issue is in there tertiary structure which causes misfolding and/- hyperphosphorylation
Using the region-cell-type-pathology structure, describe two NDDs
PARKINSONS DISEASE
Region: substantia nigra
Cell type: dopaminergic nigrostriatal neurones
Pathology: lewy bodies, neuronal loss
MND
Region: Primary motor cortex
Cell type: layer 5 pyramidal neurones
Pathology: neuronal loss, TDP-43 inclusions
State the cognitive functional domains
For each give an example of what it controls
MEMORY
- recent events, facts, encoding vs retrieval
LANGUAGE
- syntax, word-finding/naming, meaning
SOCIAL-BEHAVIOURAL
- disinhibition, apathy, loss of empathy
PSYCHIATRIC
- depression, hallucination, paranoia
VISUOSPATIAL
- wayfinding, arranging objects, copying a drawing
EXECUTIVE FUNCTION
- working memory, structured tasks
Give an example of a cognitive syndrome that can cause a deficit in the following cognitive domains:
a) memory
b) language
c) social-behavioral
d) visuospatial
a) Alzheimer’s
b) Primary progressive dysphasia
c) Frontal-temporal dementia (+ executive function loss)
d) Posterior cortical atrophy, Alzheimer’s
Give 3 examples of motor negative syndromes/symptoms
- UMN lesions
- LMN lesions
- Parkinsonism
- Apraxia
- Ataxia
Give 3 examples of motor positive syndromes/symptoms
- Tremor
- Dystonia
- Myoclonus
- Chorea
- Seizures
Give 3 examples of sleep syndromes/symptoms
- insomnia
- Decreased REM sleep
- REM sleep behavioral disinhibition
- periodic limb movements
Give 3 examples of autonomic syndromes/symptoms
- sialorrhoea
- constipation
- postural HTN
- Erectile dysfunction
- Detrusor-sphincter dyssnergia
Give 3 examples of sensory syndromes/symptoms
- insensitivity to pain
- agraphasthesia
- astereognosis
Give 5 symptoms of Parkinsons
- Parkinsonism
- Apathy
- Memory impairment
- Dystonia (cog-wheel)
- Resting tremor
- Sleep dysfunctions
- Autonomic dysfunctions
- Psychiatric dysfunctions
- Visuospatial dysfunction
- Executive function
How does MND present?
MND= UMN + LMN (corticospinal tract) damage
- Language, executive, social, depression, paranoia, behavioral dysfunctions, sialorrhoea
What information can imaging give us about NDD?
- The cortex is small (due to neuronal loss)
- However symptoms will start when neurones start to work less well: this may be before neurones die and so imaging wont always coincide –> less sensitive
This is why Alzheimers cannot be ruled out by MRI in the context of cognitive impairment
What information can a PET scan give us in NDD?
In NDD, there is neuronal loss. This means the cellular demand for glucose decreases as neurones stop working. This will proceed any MRI changes
A PET scan uses radio-labelled glucose injected into peripheral NS and its uptake in the brain is monitored
- in cancer this appears as hot spots
- in NDD this appears as cold spots
What might the PET scan of a patient with Alzheimers look like?
Cold spots affecting parietal and occipital lobes with frontal lobe sparing
What information can a DAT scan give us in NDD?
Uses radioactive tracer to visualise dopamine transporter levels
Used as diagnostic tool for Parkinsons
Describe the progression of NDD and symptoms onset
Think about specific diseases such as AD and PD
When pathology begins its asymptomatic
During the prodromal phase there is a large increase in the severity of the pathology
Once there is severe pathology this is usually when symptoms begin (in Alzheimer’s this is 10-15 years after onset)
- coupled with time between symptom onset and presentation to doctor, patients are usually late into disease by time of diagnosis
In PD, 80% of neuronal loss in substantial nigra before symptoms
What is the gene mutation responsible for Tau-related NDDs?
MAPT
