Neurodegenerative Disorders Flashcards
Give examples of neurodegenerative disorders
Alzheimer's Parkinson's Huntington's Frontal temporal dementia/picks CBGD Motor neuron disease PSP - progressive supra palsy
What are the main indications of neurodegenerative disorders ?
Loss of neurons in brain and spinal cord
Progressive symptoms
Irreversible symptoms
What is the most common neurodegenerative disorder ?
Alzheimer’s
Define dementia:
An acquired, persistent intellectual impairment involving at least 3 of these domains:
- language
- visuospatial skills
- emotion/personality
- memory
- cognitive/executive function s
It is a failure of higher brain functions
Why are the pathological markers of AD?
Cortical extracellular senile plaques and neurofibrillary tangles
What are the pathological markers of PD?
Lewy bodies- intracellular
What are the pathological markers of PSP?
Subcortical neurofibrillary tangles
What are the pathological markers of CBGD?
Cortical and subcortical achromatic inclusion bodies
What are the pathological markers of Huntingtons disease ?
Selective loss or neurons and gliosis
What are the pathological markers of picks disease ?
Selective temporal lobe atrophy and picks bodies
What was PD first described as ?
Shaking palsy in 1817
What does PD cause ?
A kinetic rigid syndrome
- loss of movement
- increased muscle tone
Do patients normally die form PD and what are their life expectancies ?
No they normally die of a complication of the disease such as bronchopneumonia or bed sores
10-15 years but some people survive decades - the drug treat,net significantly prolongs life
What are the main symptoms of Parkinson disease ?
Tremor Rigidity Speech difficulty Postural changes Akinesia
What do Parkinson’s patients do to try and help initiate movements ?
Use visual cues such as a time on a clock
What are the pathological effects of Parkinson’s disease ?
Loss of neurons in substantia nigra
Lewy bodies - spherical eosinophilic inclusion bodies
It is the dopaminergic neurones that are affected
Loss of the excitatory and inhibitory nigro-striatal pathways
Affects midbrain nuclei
What are the causes of Parkinson’s disease ?
Unknown - idiopathic
What things have caused associated disorders of Parkinson’s disease ?
Drug induced - iatrogenic- dopamine antagonist
MPTP induced - contaminated amphetamines which kills off dopamine neurons in substantia nigra causing rapid onset of Parkinson’s disease
Post encephalitic- viral illness that triggers degeneration of nerve cells in substantia nigra
What happens to the pathways in Parkinson’s disease ?
Lose indirect and direct pathways so it reduces thalamic output causing a reduction in motor output
Describe huntingtons disease
Gradual onset Normal onset is 30-50 years - younger means it's more sever Progressive Inherited Death within 10-20 years Main symptoms are chores and dementia
What are the symptoms that lead to dementia in huntingtons disease ?
Irritability
Moodiness
Antisocial behaviour- aggressive, angry and unpleasant
What are th symptoms that lead to gross chore inform movements of huntingtons disease ?
Fidgeting
Restlessness
Gross choreiform movements cause over reaching and grasping things too tightly
Where are neurons lost in huntingtons disease?
Cerebral cortex
Corpus striatum
Which neurons are the first to be affected in huntingtons disease ?
Medium sized spiny neurons containing GABA and enkephalins
What happens to neurotransmitters in huntingtons disease ?
Decrease in GABA and its enzyme GAD
Decrease in ACh and its enzyme choline acetyl transferase
Either no change to dopamine or a slight increase
What happens to the pathway in huntingtons disease ?
Lose some of the negative feedback control on dopamine causing increased dopamine output
What are the causes of huntingtons disease?
Autosomal dominant disorder
Affects shorts arm of chromosome 4
Locus 4p16.3 codes for protein Huntingtin - gives rise to poly glutamine repeat - CAG
More than 36 repeats means you have the disease
Describe progressive supranuclear palsy
Idiopathic Death within 2-12 years Affects subcortical grey matter- loss of neurons 2x more prevalent in men Causes aspiration and inanition Starts 45-75 years
What are the main symptoms of PSP?
Progressive dementia causing exaggerated emotional response
Motor disorders
- opthalmoplegia, pseudobulbar palsy and balance/posture impaired
Sometimes causes limb rigidity, bradykinesia and hyperreflexia
What is opthalmoplegia ?
Loss of eye movements
First the vertical gaze and then horizontal
What balance/postural impairments occur in PSP?
Unexplained falls
Neck extended and rigid to flexion so it’s difficult to move
What are he pseudobulbar palsy symptoms of PSP?
Facial weakness
Dysarthria
Dysphagia
Exaggerated gag reflex
What are the pathologies of PSP?
Neurodegeneration
Neurofibrillary tangles in midbrain, pons, basal ganglia, dentate nuclei of cerebellum - in all motor control areas
Decrease in da in cerebellum and caudate nucleus
What are neurofibrillary tangles ?
Aggregates of tau protein in micro tubules
Describe cortical basal ganglionic degeneration
Rare
Non inherited
Onset is Middle age/elderly
What are the symptoms of CBGD??
Bradykinesia/rigidity Clumsiness Speech- apraxia, asphasia and dysarthria Myoclonus Postural instability
What is dysarthia?
Inability to vocalise
What are the pathologies of CBGD ?
Atrophy of frontal and parietal cortex
Cell loss and gliosis in cortex, thalamus, red nucleus, lentiform nucleus, substantia nigra and locus coerulus
What are the different disorders in motor neurons disease ?
Amyotrophic lateral sclerosis - ALS- loss of both upper and lower
Primary lateral sclerosis - PLS - loss of upper
Progressive muscular atrophy - PMA - loss of lower
Pseudobulbar palsy -PBP- loss of lower
Preogressive bulbar palsy -PrBP- loss of upper
Describe ALS
Begins 30-60 years old Degen of both upper and lower( anterior horn cells) Muscle denervation 90-95% sporadic and 5-10% familial Fatal in 3-5 years
What are the symptoms on motor neurons disease ?
Bulbar 20% - chewing, swallowing, breathing and speaking
Upper extremities and lower extremities 40%
Muscle wasting and weakness
Affected muscles are easily tired, stiff and twitch
What is ALS-PDC?
Occured in chaumoro people of Guam
They ate flying foxes which act cycads that contain toxic amino acid beta-methylamino l-Alanine
What is picks disease ?
It’s the most common frontotemporal dementia - 20-25%
Onset 56-58 years
Duration 8-11 years
No known genetic factor but 45% have first degree relatives with the disorder
What are the symptoms of picks disease ?
Personality changes - inappropriate social behaviours, impulsive, neglect of hygiene
Emotional changes- apathy, depression, mania, anger and irritability
Speech- no fluency, echolalia, dysarthia, palilalia
Fm develop voracious appetites
What are the pathologies of picks disease ?
Neuronal cell loss causing astrogliosis
Swollen ballooned neurons - picks cells
What is the cause of picks disease ?
Unknown
- decrease in serotonin receptors and serotonin
Decrease in somatostatin in brain and CSF
Describe Alzheimer’s disease
Most common form of dementia Sporadic - 90% Familial - 10% Onset is usually > 60 Death within 5-10 years - due to infection, inanition or haemorrhagic stroke
What are the pathologies of ad ?
Atrophy of cortex- gyri shrink and sulci eidden and lose grey matter
Plaques and neurofibrillary tangles - start in enorhinal cortex-hippocampus-parahippocampus-cingulate gyrus- cortex
What are the plaques in ad ?
Proteinacious structure Made up of amyloid beta protein Surround by dystrophic neurites- neuronal processes that show kinking and strange structure around plaques Extracellular Reactive gliosis around them
What are neurofibrillary tangles in ad ?
Flame like
Intracellular inclusions of hyperphosphorylated tau protein
What neurons are lost in ad ?
Cholinergic neurons
Lose nAChR and ChAT
What are the earliest symptoms of ad ?
Short term memory loss Disorientation- time then place Visuospatial orientation Apraxia Aphasia, anomia acalculia
What are the later symptoms of ad ?
Loss of social skills
Psychosis and paranoia/hallucinations/delusions
Bradykinesia/rigidity
What are the latest symptoms of ad ?
Mutism
Bedridden
Incontinence
How is ad assessed ?
Mini mental state examination
What is mild cognitive impairment ?
Can precede ad
Complaint of memory loss
Have intact activities of daily living
What is mild ad ?
Forgetfulness Short term memory loss Impaired daily actives Loss of hobbies and interests Repetitive questions
What is moderate ad ?
Progression do cognitive deficits
Dysexecutive syndrome
Further impaired daily activities
Emergence of behavioural and psychological symptoms
What is severe ad ?
Agitation
Altered sleep pattern
Assistance required for feeding, dressing and bathing
Established behavioural and psychological symptoms
What is very severe ad ?
Bed bound
No speech
Incontinent
Basic psychomotor skills lost
What are the causes of ad ?
Genetic
-trisomy 21- beta amyloid protein resides on this
- familial - ApoE4
Amyloid
- forms plaques Nd it’s thought the build up of these causes death of neurons
Trauma
- risk with head injury or with hypoxia/anoxic episodes
What pathway forms amyloid beta proteins ?
The beta pathway not the alpha
What is the amyloid hypothesis ?
States that amyloid beta protein is overproduced in ad and will give rise to aggregates of the protein binding to itself and forming plaques which give rise to the excitotoxcity that causes the symptoms of ad
