Neurodegenerative Disorders Flashcards
Identify examples of Neurodegenerative disorders.
- Parkinson’s disease
- Alzheimer’s disease
- Huntington’s disease
- Motorneurone diseases
- Spinocerebellar degenerations
- Spongiform encephalopathies
- FTD, other dementias
- Progressive MS
- Others
Identify possible factors which contribute to neurodegeneration.
Protein handling disorders Activation of cell death pathways Mitochondrial dysfunction Lack of growth factors Oxidative stress Ionic dysequilibrium Excito- toxicity Immune attack Toxins
Identify genes associated with ALS.
- Superoxide Dismutase 1
- TAR DNA Binding Protein (TDP-43)
- Fused in Sarcoma (FUS)
- C9orf72 (most common)
Identify possible mechanisms of neuronal death in neurodegenerative disorders.
1) Excitotoxicity (through glutamate, and calcium overload)
2) Oxidative Stress (result of excessive production of reactive oxygen species)
3) Apoptosis (Many different signalling pathways can result in apoptosis, but in all cases the final pathway resulting in cell death is the activation of a family of proteases (caspases), which inactivate various intracellular proteins)
Identify the main examples of motorneuron diseases.
- Amyotrophic Lateral Sclerosis
- Progressive Muscular Atrophy (LMN)
- Primary Lateral Sclerosis (UMN)
- Spinal Muscular Atrophy (groups of spinal nerves degenerate at different times, relatively slowly)
- Lou Gehrig’s disease
Does ALS have upper, or lower motor neuron signs ?
Both (brisk reflexes in muscles that are fasciculating)
Identify a treatment used for ALS, describing its mode of action. How long does it prolong life ?
RILUZOLE
- Blocks TTX Na channels
- Reduces Glutamate release (Calcium block)
- Increases astrocyte glutamate uptake
- Enhances GABA activity
- Enhances BDNF action
Prolongs life by about 3 months
Identify the main features of dementia.
1. Neuropsychological deficits Amnesia (memory) Aphasia (speech) Agnosia (recognising things) Apraxia (complex movements)
- Neuropsychiatric features
(Behavioural and psychological symptoms, BPSD)
Psychiatric symptoms
Behavioural disturbances - Activities of daily living
Instrumental
Basic
Describe the cognitive assessment for a patient with possible dementia.
1) Frontal lobes – sequencing and fluency
• Luria hand sequencing task (repeat this sequence of movements)
• Verbal fluency 1 minute words F,A, S, animals
2) Temporal lobes – memory, speech (L)
• Address test
• Object recall
• Serial 7s
3) Parietal lobes – Spatial awareness (R), Language (L) • Clock face (draw clockface) • Naming objects • Drawing cube, interlocking infinity • Agnosia
Identify specific tool for dementia screening.
MMSE
ACE-R Psychometrics (more sensitive, more specific)
Describe diagnosis of dementia.
- Dementia is conventionally diagnosed when progressive cognitive decline has occurred, and this has had noticeable impacts upon a person’s ability to carry out important everyday activities.
- The pathological changes in the brain that will eventually lead to the symptoms of dementia are likely to have commenced well in advance (15-30 years) of the time at which the person’s symptoms would first have been noticed
Define mild cognitive impairment.
• MCI requires subjective memory impairment and cognitive impairment not meeting dementia diagnostic criteria (in particular with no impairment in core ADLs)
Can be reversible (conversion by n omeans inevitable, even for MCI up to 25% in some studies show subsequent recovery of normal cognitive function)
Describe the main presentation of Alzheimer’s disease.
• Presents with early memory disturbance, progressing to dyspraxia and dysphasia, eventually immobile and mute
Identify the main histological processes of AD.
1) Neurofibrillary tangles
• predominantly composed of tau
• normal tau stabilises microtubules
• tau is hyperphosphorylated in NFTs and forms paired helical filaments
2) Amyloid plaques
• Extracellular proteinaceous deposits
• Largely composed of Aβ peptides that aggregate together to form fibrils–either diffuse or neuritic (surrounded by dystrophic neurites)
What are the main CSF markers investigated for the diagnosis and management of AD, almost all immunoassay ?
– amyloid-β42 (Aβ42)
– Total tau (t-tau)
– Phosphorylated tau (p-tau)
(but no CSF marker can reliably predict development of AD in healthy individuals)
Real Time Quake-Induced Conversion (RT QuIC) is a new way of looking for levels of Aβ42, one of the components of APP, in spinal fluid of patient which are going on to develop AD.
Identify neurochemical changes in AD.
- Marked loss of ACh, related to neuronal loss from nucleus basalis of Meynert
- Loss of GABA from cortex secondary to neuronal loss
- Serotonin (5HT) input from dorsal raphe nuclei reduced
- Noradrenaline input from locus ceruleus reduced
