LC 3.5 Ageing Brain Flashcards

1
Q

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

A

It doubles

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2
Q

What makes up the majority of this increase in volume?

A

Grey matter proliferation

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3
Q

What happens to the white matter during this time?

A

Similar complexity

Myelination of axons occurs

Only a small increase in volume

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4
Q

In which direction does brain maturation occur in?

A

Posterior -> anterior

Central -> peripheral parts

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5
Q

Which processes is myelination essential for?

A

Higher brain processes

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6
Q

When does myelination occur?

A

From well before birth into adulthood (middle age)

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7
Q

What can stimulate myelination?

A

Learning a new skill

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8
Q

What happens to the brain volume with ageing?

A

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

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9
Q

What causes the shrinking of the brain with age?

A
  • 10% neuronal loss in cortex

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

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10
Q

Where other than the cortex are neurones lost with age?

A
  • Substantia nigra
    • Hippocampus
    • Amygdala
    • Cerebellar purkinje cells
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11
Q

What synaptic changes occur with age?

A

Regression of dendrites

Reduction in synaptic density

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12
Q

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

A

Dentate gyrus

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13
Q

How does the brain respond to regression of dendrites?

A

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

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14
Q

What cerebrovascular changes occur with ageing?

A
  • Decreased blood flow
    • Decreased cerebral blood volume
    • Blood vessels become less distensible
    • Blood vessels increase in thickness, reducing lumen
    • Increased blood brain barrier permeability
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15
Q

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

A
  • Reduced glucose oxidation

* NO CHANGE in ability for brain cells to extract oxygen

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16
Q

What changes occur to myelin with age?

A

Myelin pallor

Malformation of sheaths

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

17
Q

What intracellular damage accumulates in neurones of the brain?

A

Damaged proteins

Dysfunctional mitochondria

Lipofuscin accumulation

Reduction in AMPA and NMDA

18
Q

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

A

Amyloid proteins

Tau

19
Q

What causes lipofuscin accumulation?

A

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

20
Q

What cognitive changes are seen with age and why?

A

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

21
Q

What is the most common age-related neurodegenerative disease?

A

Alzheimer’s disease

22
Q

How do Alzheimer’s Disease patients typically present?

A

Disturbances of recent memory for over a year

Attention, language and visuospatial deficits

23
Q

What is the survival for Alzheimer’s dementia?

A

3-10 years depending on age of onset

24
Q

What are the risk factors for Alzheimer’s?

A

Age

APOe3 allele

Low educational attainment

CVD

Diabetes

25
Why is high educational attainment protective of Alzheimer's?
Those who learned more have myelination, and so it takes longer for this to degenerate to beyond the Alzheimer's threshold
26
What neuromorphological changes occur with Alzheimer's?
Severe increase in size of ventricles and gyri, shrinking of sulci In particular parahippocampal gyrus is reduced.
27
How is Alzheimer's definitively diagnosed?
presence of plaques and tangles upon post mortem examination
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?
Amyloid-Beta 40-42 (normal is 39 long) Amyloid precursor protein (from Chromosome 21)
29
How do senile plaques cause the symptoms of Alzheimer's?
Overproduction or reduced clearance causes accumulation and then synaptic and metabolic damage
30
What is the main protein component of neurofibrillary tangles and what shape are they on a slide?
Tau protein They 'fill' the neuronal cell body and proximal dendrite/axon causeing a 'flame like' shape
31
What causes Tau protein buildup?
Hypoactivity of kinases hyperactivity of phosphatases
32
What condition are survivors of stroke likely to suffer from in the future? What is the mechanism for this?
Dementia Caused by: • Blood brain barrier leakage • Stroke initiates amyloid deposition • Chronic hypoperfusion
33
The process by which amyloid-beta causes dementia is what'?
Amyloid cascade
34
What are the motor symptoms of Parkinson's?
Resting tremor Rigidity Bradykinesia postural instability
35
What is the pathology of Parkinson's?
Lewy bodies of alpha-synuclein accumulate