Lecture 3 Neurology Theme - Dementia

Question 1

Name the 4 types of dementia.

Answer 1

Alzheimer’s (62%)
Vascular (17%)
Levy Body (4%)
Frontotemporal (2%)

Question 2

Describe the main features of Alzheimer’s.

Answer 2

Hippocampus atrophy
Enlargement of ventricles
Neurofibrillary tangles (tau)
Amyloid plaques (amyloid-beta)

Question 3

What 3 genetic mutations can cause early onset AD?

Answer 3

APP, PSEN-1, PSEN-2

Question 4

What gene is involved with late onset AD?

Answer 4

Apolipoprotein E

Question 5

Describe the main features of vascular dementia.

Answer 5

Problems with the blood supply to the brain.
Small stroke in the cortex = multi-infarct
Damage to small vessels = Binswanger’s

Question 6

What increases the risk of vascular dementia?

Answer 6

Lifestyle factors - smoking, high fat diet.
Diabetes
Hypertension
Atrial fibrillation

Question 7

Describe the main features of Lewy body dementia.

Answer 7

Visual hallucinations
Parkinsonism
Cognitive dysfunction presents within 2 years.

Question 8

What are Lewy-Bodies?

Answer 8

Abnormal protein structures in the cortex and basal ganglia that disrupt neurotransmitter function.

Question 9

Describe the main features of frontotemporal dementia.

Answer 9

Changes in behaviour and language.

Question 10

Describe Creutzfeldt-Jakob disease.

Answer 10

Subtle changes in memory followed by rapid dementia.
Mainly a prion disease where protein aggregates spread from one cell to another and cause abnormal folding.
Shown by spongiform transformation in cerebral cortex, caudate nucleus and putamen.

Question 11

What are the other sub-types of dementia?

Answer 11

Huntington’s
Alcohol related dementia
Progressive supranuclear palsy.

Question 12

What are modifiable risk factors for dementia?

Answer 12

Smoking
Atherosclerosis
Alcohol
Low education

Question 13

What are non-modifiable risk factors for dementia?

Answer 13

Genetics
Age
MCI

Question 14

What can cognitive symptoms be medicated with?

Answer 14

AcH inhibitors
NMDA
Antagonists slow progression of decline.

Question 15

What are some ACE inhibitor side effects?

Answer 15

Incontinence
Nausea
Anorexia
Insomnia

Question 16

What are some NMDA antagonist side effects?

Answer 16

Dizziness
Confusion
Constipation
Hypertension

Question 17

What are some cognitive assessments for dementia?

Answer 17

MMSE - <23 = mild, <18 = severe
MoCA - assess attention, concentration memory and language.

Question 18

What types of imaging can be done to identify dementia?

Answer 18

CT, MRI and SPECT

Question 19

What is the assessment for vascular dementia?

Answer 19

Hachinski Ischaemia Score = 13/18 or 5 items from abrupt onset, stepwise deterioration, emotional incontinence, depression, hypertension and atherosclerosis.

Question 20

What causes frontotemporal lobe degeneration?

Answer 20

Tau forms neurofibrillary tangles.
Tau moves down microtubule, becomes hyperphosphorylated and loses ability to bind to microtubules.
Promotes aggregation through microtubule binding domains.

Question 21

What is amyloid-beta pathology?

Answer 21

In senile plaques it is 40-42 aa long.
Cleavage of APP by beta and gamma secretes releases amyloid beta 42 which aggregates into small oligomers then fibrils.

Question 22

What is cholinergic monotherapy?

Answer 22

Decreased Ach leads to reduced attention and cognition, especially loss of cholinergic neurons in the basal forebrain.
Aim is to decrease choline acetyltransferase and alter the patterns of acetylcholinesterase.

Question 23

What are some names of drugs that are good for cholinergic monotherapy?

Answer 23

Donepezil
Rivastigmine
Galanthamine

Question 24

What are the side effects of cholinergic monotherapy?

Answer 24

Turns on all taps so incontinence, oral, nasal and gastrointestinal secretions.

Question 25

Describe NMDA receptor antagonists and name an example.

Answer 25

Memantine.
Excess calcium in nerve cells causes apoptosis so memantine slows calcium influx by glutamate receptor activation to slow neuron loss and decline.