Memory Disorders Part 2

Question 1

Alzheimer’s disease

Answer 1

• Progressive disorder that results in dementia and death
• Early symptoms: selective declines in memory (mild cognitive impairment)
• Later symptoms: confusion, irritability, anxiety, and deterioration of speech
• Advanced stages: difficulties with even simple responses (eg. Swallowing, bladder control)
• Strong genetic component – if your parents have it, you have a 50% chance

Question 2

3 defining characteristics of Alzheimer’s

Answer 2

• neurofibrillary tangles
• amyloid plaques
• decrease in brain volume

Question 3

defining characteristics: neurofibrillary tangles

Answer 3

Microtubules become hyperphosphorylated (more phosphate), breaking them down and leading to tau tangles

Question 4

defining characteristics: amyloid plaques

Answer 4

• Scar tissue; first signs of Alzheimer’s
• Amyloid normally involved in plasticity
• First seen in temporal lobe (in parts involving memory, ie. Hippocampus)

Question 5

defining characteristics: decrease in brain volume

Answer 5

Substantial decrease in brain volume due mainly to loss/shrinkage of neuronal processes (synapse loss), but also due to loss of neurons

Question 6

Alzheimer’s biomarkers

Answer 6

• Low beta-amyloid levels in cerebrospinal fluid
• High tau levels in cerebrospinal fluid
• PET imaging of beta-amyloid levels
• PET imaging of tau and hyperphosphorylated tau
• Decrease in hippocampal volume (MRI)
• Decreases in brain metabolism – becomes hypoactive; uses less glucose (FDG-PET)

Question 7

2 theories of pathogenesis

Answer 7

• neurofibrillary/tau hypothesis

- amyloid cascade hypothesis

Question 8

theories: neurofibrillary/tau hypothesis

Answer 8

• Tau is causing degeneration & Alzheimer’s

- However, when testing this in animal models, it doesn’t cause amyloid plaques, so it might not be legit

Question 9

theories: amyloid cascade hypothesis

Answer 9

• amyloid plaques causing Alzheimer’s
• Most widely-accepted hypothesis
• Brains of people with Downs Syndrome produce more plaques, and those people have much higher rates of Alzheimer’s than the rest of the population
• Issue: amount of plaques doesn’t always correlate with degeneration

Question 10

treatment

Answer 10

• Cholinergic (ACh) agonists – eg. Acetylcholinesterase inhibitors
• NMDAR (glutamate) antagonist (memantine)
• Lithium
• Physical exercise, environmental enrichment -> slows down deterioration