25.3 Cognitive Disorders of old age

Question 1

What are some causes of dementia mentioned in the spec and how common are they?

[IMPORTANT]

Answer 1

• Alzheimer’s disease -> 60-80%
• Fronto-temporal dementia -> 5-20%
• Vascular dementia -> 5-15%
• Lewy body disease -> 2-8%
• Creutzfeldt–Jakob disease (prion disease) -> Rare

Question 2

For dementia caused by Alzheimer’s disease, describe the prevalence, pathology and the primary site/features.

Answer 2

• Prevalence: 60-80%
• Pathology: Amyloid plaques and tau tangles
• Site/Features: Medial temporal lobe and parietal lobe -> Then progresses to frontal areas

Question 3

For fronto-temporal dementia, describe the prevalence, pathology and the primary site/features.

Answer 3

• Prevalence: 5-20%
• Pathology: Several subtypes involving the aggregation of proteins such as tau, TDP43 or FUS
• Site/Features: Frontal lobe (behavioural symptoms) or temporal lobe (semantic/aphasia symptoms)

Question 4

For vascular dementia, describe the prevalence, pathology and the primary site/features.

Answer 4

• Prevalence: 5-15%
• Pathology: Vascular pathology (e.g stroke)
• Site/Features: Can be anywhere, Sudden changes, Step-wise progression

Question 5

For dementia with Lewy bodies, describe the prevalence, pathology and the primary site/features.

Answer 5

• Prevalence: 2-8%
• Pathology: Lewy bodies (also seen in Parkinson’s disease)
• Site/Features: Motor symptoms, Sleep disturbance (similar to in Parkinson’s disease), Visual hallucinations, Fluctuating deficits

Question 6

For dementia due to Creutzfeldt–Jakob disease, describe the prevalence, pathology and the primary site/features.

Answer 6

• Prevalence: Rare
• Pathology: Prion protein deposition
• Site/Features: ADD

Question 7

What is the pathology of AD characterised by?

Answer 7

AD characterised by 2 imp microscopic features: EC amyloid plaques + IC tau tangles.

Question 9

How do the plaques form in AD?

Answer 9

APP (amyloid precursor protein) –abnormal processing→ Aβ
*Aβ fragments aggregate → oligomers → long insoluble fibril.
*Imbalance between Aβ production + clearance → accumulation of plaques

Question 10

What is the amyloid cascade hypothesis?

Answer 10

Amyloid cascade hypothesis → suggests Aβ = causative agent of AD pathology, directly → other elements of disease. (e.g. neurofibrillary tangles/ toxicity/ memory impairment)

Question 11

What counteracts the amyloid cascade hypothesis?

Answer 11

No all amyloidogenesis show AD pathology, some studies indicate tau required for Aβ toxicity.
*Tau (microtubule associated protein) –hyperphosphorylation → IC tau deposits
*Proteins aggregate into NFTs.

Question 12

What parts of the brain are involved in Alzheimer’s disease according to the spec?

Answer 12

Basal forebrain cholinergic systems

Question 13

What treatments are there currently available for AD?

Answer 13

*Anti-cholinesterases
*NMDA antagonists
*ABs against Aβ

Question 14

What is the rational behind the use of anti-cholinesterases to treat AD?

Answer 14

Cholinesterase inhibitors (e.g. tacrine/ donepezil) → ↑ level of ACh in brain, compensating for cholinergic neuronal loss.
*Only ↓ symptoms, not progression.

Question 15

What is the rational behind the use of NMDA antagonists to treat AD?

Answer 15

NMDA antagonist (Memantine) → blocks excessive glutamatergic neurotransmission.
*For moderate - severe confusion (dementia) related to AD.
*Symptomatic relief.