LC 3.5 Ageing Brain

Question 1

By how much does the volume of the brain increase in the first year of life?

Answer 1

It doubles

Question 2

What makes up the majority of this increase in volume?

Answer 2

Grey matter proliferation

Question 3

What happens to the white matter during this time?

Answer 3

Similar complexity

Myelination of axons occurs

Only a small increase in volume

Question 4

In which direction does brain maturation occur in?

Answer 4

Posterior -> anterior

Central -> peripheral parts

Question 5

Which processes is myelination essential for?

Answer 5

Higher brain processes

Question 6

When does myelination occur?

Answer 6

From well before birth into adulthood (middle age)

Question 7

What can stimulate myelination?

Answer 7

Learning a new skill

Question 8

What happens to the brain volume with ageing?

Answer 8

Reduces in size from age 20

After 40, brain volume decreases by 5% per decade
• Increase in ventricular size
• Gyri shrink
• Sulci widen

Reduction in size of subcortical structures

White matter increases in volume until middle age then declines exponentially

Question 9

What causes the shrinking of the brain with age?

Answer 9

• 10% neuronal loss in cortex

* Other brain regions have shrinkage of cell bodies without loss of neurones

Question 10

Where other than the cortex are neurones lost with age?

Answer 10

• Substantia nigra
  
  • Hippocampus
  • Amygdala
  • Cerebellar purkinje cells

Question 11

What synaptic changes occur with age?

Answer 11

Regression of dendrites

Reduction in synaptic density

Question 12

Where is the exception to the rule of reduction of dendrites with age?

Answer 12

Dentate gyrus

Question 13

How does the brain respond to regression of dendrites?

Answer 13

Neighbouring dendrites sprout a new dendritic limb to maintain the neural connection with the regressing cell

Question 14

What cerebrovascular changes occur with ageing?

Answer 14

• Decreased blood flow
  
  • Decreased cerebral blood volume
  • Blood vessels become less distensible
  • Blood vessels increase in thickness, reducing lumen
  • Increased blood brain barrier permeability

Question 15

What changes are caused by reduced blood flow to the brain?

Answer 15

• Reduced glucose oxidation

* NO CHANGE in ability for brain cells to extract oxygen

Question 16

What changes occur to myelin with age?

Answer 16

Myelin pallor

Malformation of sheaths

Reduction in amount (by up to 45% by length)

Question 17

What intracellular damage accumulates in neurones of the brain?

Answer 17

Damaged proteins

Dysfunctional mitochondria

Lipofuscin accumulation

Reduction in AMPA and NMDA

Question 18

What is the main damaged protein which accumulates in the ageing brain?

Answer 18

Amyloid proteins

Tau

Question 19

What causes lipofuscin accumulation?

Answer 19

Post-mitotic neurones dospose of damaged proteins and organelles by sequesting them in a double membrane and transport them to a lysosome for degradation.

Bi-product of this is lipofuscin

Question 20

What cognitive changes are seen with age and why?

Answer 20

Slow cognitive decline due to changes in white matter and dendritic desity

Question 21

What is the most common age-related neurodegenerative disease?

Answer 21

Alzheimer’s disease

Question 22

How do Alzheimer’s Disease patients typically present?

Answer 22

Disturbances of recent memory for over a year

Attention, language and visuospatial deficits

Question 23

What is the survival for Alzheimer’s dementia?

Answer 23

3-10 years depending on age of onset

Question 24

What are the risk factors for Alzheimer’s?

Answer 24

Age

APOe3 allele

Low educational attainment

CVD

Diabetes

Question 25

Why is high educational attainment protective of Alzheimer’s?

Answer 25

Those who learned more have myelination, and so it takes longer for this to degenerate to beyond the Alzheimer’s threshold

Question 26

What neuromorphological changes occur with Alzheimer’s?

Answer 26

Severe increase in size of ventricles and gyri, shrinking of sulci

In particular parahippocampal gyrus is reduced.

Question 27

How is Alzheimer’s definitively diagnosed?

Answer 27

presence of plaques and tangles upon post mortem examination

Question 28

What are senile plaques primarily composed of? How many amino acids does it have?
What is this derived from and on what chromosome is this found?

Answer 28

Amyloid-Beta

40-42 (normal is 39 long)

Amyloid precursor protein (from Chromosome 21)

Question 29

How do senile plaques cause the symptoms of Alzheimer’s?

Answer 29

Overproduction or reduced clearance causes accumulation and then synaptic and metabolic damage

Question 30

What is the main protein component of neurofibrillary tangles and what shape are they on a slide?

Answer 30

Tau protein

They ‘fill’ the neuronal cell body and proximal dendrite/axon causeing a ‘flame like’ shape

Question 31

What causes Tau protein buildup?

Answer 31

Hypoactivity of kinases

hyperactivity of phosphatases

Question 32

What condition are survivors of stroke likely to suffer from in the future? What is the mechanism for this?

Answer 32

Dementia

Caused by:
• Blood brain barrier leakage
• Stroke initiates amyloid deposition
• Chronic hypoperfusion

Question 33

The process by which amyloid-beta causes dementia is what’?

Answer 33

Amyloid cascade

Question 34

What are the motor symptoms of Parkinson’s?

Answer 34

Resting tremor
Rigidity
Bradykinesia
postural instability

Question 35

What is the pathology of Parkinson’s?

Answer 35

Lewy bodies of alpha-synuclein accumulate