LC 3.5 Ageing Brain Flashcards
By how much does the volume of the brain increase in the first year of life?
It doubles
What makes up the majority of this increase in volume?
Grey matter proliferation
What happens to the white matter during this time?
Similar complexity
Myelination of axons occurs
Only a small increase in volume
In which direction does brain maturation occur in?
Posterior -> anterior
Central -> peripheral parts
Which processes is myelination essential for?
Higher brain processes
When does myelination occur?
From well before birth into adulthood (middle age)
What can stimulate myelination?
Learning a new skill
What happens to the brain volume with ageing?
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
What causes the shrinking of the brain with age?
- 10% neuronal loss in cortex
* Other brain regions have shrinkage of cell bodies without loss of neurones
Where other than the cortex are neurones lost with age?
- Substantia nigra
- Hippocampus
- Amygdala
- Cerebellar purkinje cells
What synaptic changes occur with age?
Regression of dendrites
Reduction in synaptic density
Where is the exception to the rule of reduction of dendrites with age?
Dentate gyrus
How does the brain respond to regression of dendrites?
Neighbouring dendrites sprout a new dendritic limb to maintain the neural connection with the regressing cell
What cerebrovascular changes occur with ageing?
- Decreased blood flow
- Decreased cerebral blood volume
- Blood vessels become less distensible
- Blood vessels increase in thickness, reducing lumen
- Increased blood brain barrier permeability
What changes are caused by reduced blood flow to the brain?
- Reduced glucose oxidation
* NO CHANGE in ability for brain cells to extract oxygen
What changes occur to myelin with age?
Myelin pallor
Malformation of sheaths
Reduction in amount (by up to 45% by length)
What intracellular damage accumulates in neurones of the brain?
Damaged proteins
Dysfunctional mitochondria
Lipofuscin accumulation
Reduction in AMPA and NMDA
What is the main damaged protein which accumulates in the ageing brain?
Amyloid proteins
Tau
What causes lipofuscin accumulation?
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
What cognitive changes are seen with age and why?
Slow cognitive decline due to changes in white matter and dendritic desity
What is the most common age-related neurodegenerative disease?
Alzheimer’s disease
How do Alzheimer’s Disease patients typically present?
Disturbances of recent memory for over a year
Attention, language and visuospatial deficits
What is the survival for Alzheimer’s dementia?
3-10 years depending on age of onset
What are the risk factors for Alzheimer’s?
Age
APOe3 allele
Low educational attainment
CVD
Diabetes
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
What neuromorphological changes occur with Alzheimer’s?
Severe increase in size of ventricles and gyri, shrinking of sulci
In particular parahippocampal gyrus is reduced.
How is Alzheimer’s definitively diagnosed?
presence of plaques and tangles upon post mortem examination
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)
How do senile plaques cause the symptoms of Alzheimer’s?
Overproduction or reduced clearance causes accumulation and then synaptic and metabolic damage
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
What causes Tau protein buildup?
Hypoactivity of kinases
hyperactivity of phosphatases
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
The process by which amyloid-beta causes dementia is what’?
Amyloid cascade
What are the motor symptoms of Parkinson’s?
Resting tremor
Rigidity
Bradykinesia
postural instability
What is the pathology of Parkinson’s?
Lewy bodies of alpha-synuclein accumulate
