1. Cellular Degeneration and Dementia
By Joshua Bower Easter Revision Questions?

2. Degeneration Describe the process of normal cellular aging
Explain the changes in function associated with cellular aging
Use first principles to explain the changes you would see with defects in cell aging
Use the neurodegenerative diseases to explain how cellular stress can lead to accelerated degeneration of cells
Outline the microscopic and ultrastructural changes you would see in degenerating cells

3. Give TWO examples of cellular processes which can lead to cellular aging [2]
Reduced ATP
Mitochondrial damage
Ca2+ entry
Membrane damage
Protein misfolding
Reactive oxygen species

4. List THREE outcomes of cellular ageing [3]
Reduced capacity to function
Reduced capacity to respond to injury
Cell death
Apoptosis vs necrosis

5. List THREE changes leading to cellular ageing [3]
Decreased cellular replication
E.g. by p16INK4a, DNA damage
Accumulation of genetic and metabolic changes
E.g. balance between metabolic damage and repair
Reactive oxygen species-induced damage

6. Reactive oxygen species injury cells by what THREE mechanisms? [3]
Membrane lipid peroxidation
Interaction with proteins
DNA damage

7. What is Werner syndrome?
Rare, autosomal recessive disorder causing premature ageing (progeria)
Causes decreased cellular replication

8. What is Friedreich’s ataxia?
Autosomal recessive disorder leading to spinocerebellar degeneration
Leads to axon loss and gliosis
Mitochondrial dysfunction
Decreased ATP
Reactive oxygen species
DNA damage
Reduced frataxin protein
Where are the spinocerebellar tracts?

9. Neuro Flashback – Name FIVE types of glial cells [5]
Astrocytes
Oligodendrocytes
Schwann cells
Ependymal cells
Microglia
Where is this?

10. What is ALS? Amylotrophic lateral sclerosis 1 of 5 MND subtypes
Reduced capacity to detoxify cells OR misfolded proteins causes ER stress >> cell injury
Affects the myelinated fibres of the corticospinal tracts

11. Motor Neurone Disease Subtypes

12. Dementia
Explain the scientific basis for neurological and psychiatric presentations
Explain the causes and investigation of neurological and psychiatric problems
Describe how to do cognitive assessment in the context of undertaking a psychiatric mental state examination
Distinguish delirium from dementia

13. A 75 year old man is found wandering in the streets in his dressing gown in the middle of winter. He tells you he got a bit lost on the way to the shops. Differential diagnosis?
Dementia
Delirium
Substance misuse
Hypoxia
Head injury
Electrolyte imbalance
Pseudodementia

14. Distinguish delirium from dementia [5]
Onset
Rapid
Gradual
Course
Fluctuating
Progressive
Consciousness
Impaired
Clear
Speech
Dysarthria
Normal
Memory and attention
STM affected (recent change)
Fluctuating attention
Poor memory (gradual loss)
Inattention
Important to obtain a collateral history

15. List FOUR possible causes of delirium [4]
Drugs
Electrolyte/fluid imbalance
Lack of drugs (withdrawal, delirium tremens)
Infection
Reduced sensory input (vision/hearing loss)
Intracranial (post-stroke)
Urinary difficulties (UTI, catheter) MI

16. What are the clinical features of dementia?
Cognitive impairment associated with a decline in self-care and an inability to perform ADLs
Issues with:
Memory
Problem-solving
Judgement
Attention
Orientation
Language

17. How can dementia be investigated clinically?
History
Mini-mental state exam (MMSE)
Score out of 30
<27 means cognitive impairment
Bad for fronto-temporal dementia
Addenbrooke’s cognitive assessment
Incorporates MMSE and frontal lobe assessment
GPCOG – GP cognitive assessment
CT scan

18. What is pseudodementia?
Dementia caused by depression
Not caused by brain damage
Treated with anti-depressants

19. What is the commonest form of dementia?
Alzheimer’s

20. What TWO pathological findings would confirm Alzheimer’s disease, and what is the protein involved in each? [2+2]
Plaques – beta-amyloid
Amyloid precursor proteins are directly neurotoxic and cause inflammation
Tangles – tau-protein
Involved with microtubule stabilisation. When hyperphosphorylated, prevent binding so microtubules degenerate affecting cellular function

21. What CT findings are suggestive of Alzheimer’s? [3]
Shrinkage of cerebral hemispheres
Widened sulci
Enlarged ventricles

22. What class of drugs can be used to treat Alzheimer’s
What class of drugs can be used to treat Alzheimer’s? Give an example [1+1]
Acetylcholinesterase inhibitors
Donepezil
Rivastigmine
Neostigmine
Galantamine
These stabilise the condition, slow decline and postpone onset of severe dementia
Or NMDA-R antagonists if MMSE <12 e.g. memantine

23. Give TWO side effects of AChesterase inhibitors [2]
Think dryness
Dry mouth
Blurred vision
Urinary retention
Constipation
Tachycardia
Confusion
N&V
Dizziness

24. What is vascular dementia?
Aka multi-infarct dementia
Dementia following cerebral infarction – patients can experience sudden decline, then plateau (step-wise deterioration)
Emboli can cause sudden decline, with subsequent improvements in specific areas over time (e.g. speech)
Treatment? Reduce risk factors!

25. What is mixed dementia?
Alzheimer’s + vascular dementia

26. What are Lewy bodies? What THREE diseases are they associated with?
Abnormal protein aggregates of alpha-synuclein which can form in neurones in the cerebral cortex
Associated with Lewy Body Dementia, Alzheimer’s and Parkinson’s disease dementia

27. How can Lewy body dementia and Parkinson’s disease be distinguished?
In PD dementia, motor symptoms present for ~1yr prior to dementia onset
In LBD, memory symptoms occur first, or both occur together

28. Give an example of a frontotemporal dementia
Give an example of a frontotemporal dementia. How can it be distinguished from Alzheimer’s?
Pick’s disease
Build up of tau-protein into Pick bodies
In Pick’s disease, character and behaviour changes develop before memory loss. May also have speech problems
There are 3 broad types of FTD for you to look up

29. Give an example of an organic dementia
Creutzfeld-Jakob disease
Prion disease where abnormal folding of prions leads to gliosis, synaptic and neuronal loss
Can be transmissible person-to-person
Sporadic (idiopathic), variant (bovine spongiform encephalopathy) or familial (inherited)
HIV/AIDS–associated dementia
Can occur in up to 40%
Neurosyphilis (Treponema pallidum)
Viral encephalitis (often HSV)

30. Thank you