3.5 Brain ageing

Question 1

How does the brain grow?

Answer 1

Myelination occurs into adulthood and new myelin can be continually generated.
White matter volume can increase after a few weeks practising a new skill.
white matter can continue to increase till age of 50

Question 2

When can age related brain reductions begin to show up?

Answer 2

Age 20

Whole brain volume declines by ~5% per decade after the age of 40

Question 3

What is the most consistently declining part of the brain?

Answer 3

The most consistent change is a decrease in GM volume which declines linearly across the life span.

Question 4

What happens to the gyro and sulci with age?

Answer 4

Gyri are shrinking and sulci are widening - shrinking of brain with advancing age

Question 5

What percentage of neurons in the cortex are lost?

Answer 5

10% loss of neurons in the cortex.

Question 6

Where can cell body shrinkage be seen in the brain?

Answer 6

Other brain regions show a shrinkage of cell bodies without loss. - loss of neurons in substantia nigra, hippocampus, cerebellum and amygdala

Question 7

What are the synaptic changes of the brain?

Answer 7

Changes in dendritic branching and arbour have been reported
Dendritic sprouting as a compensatory mechanism
A loss of white matter and synaptic spines

Question 8

What happens to layer 5 of the cortex?

Answer 8

Layer 5 of cortex - regression of dendrites - in dentate gyrus the abror can increase in complexity till mid 80s
A reduction in synpatic density and synpatic spines in excitatory neurons. If one dendrite is lost or retrsacted - synpatic cell will lose transmission - neighbouring dendrite will sprout - continue neuronal transmission

Question 9

What are the vascular changes seen in the brain?

Answer 9

Decreased…
Cerebral blood flow
Cerebral metabolic rate for oxygen
Cerebral blood volume without significant change in oxygen extraction
Glucose Oxidation
Changes within the blood vessels. - less elastic - blood vessels are more stresse - exacerbated by atherosclerosis and hypertension
Increased permeability of the blood brain barrier

Question 10

What are the myelin changes seen in the brain?

Answer 10

White matter loss is not linear, accelerates after the age of 50.
Histopathology reveals:
• Myelin pallor
• Loss of myelinated fibres
• Malformation of myelin sheaths
Total length of myelinated axons is reduced by 27- 45% in old age.

Question 11

What is the accumulation of damage found in the brain?

Answer 11

Accumulation of damaged proteins – Amyloid Accumulation of dysfunctional mitochondria
Accumulation of Lipofuscin - gets rid of damaged proteins - lysosomal digestion
Reduction in key gene transcripts – AMPAR, NMDAR - glutamate
Substantia nigra, hippocampus and choroid plexus damage

Question 12

What are the cognitive changes seen?

Answer 12

Slowly progressive decline in cognitive ability.
• Difficulty separating mild cognitive decline associated with ageing from early stages of AD - alzeighmers
Age-associated cognitive decline (AACD), cognitive test scores 1SD below age matched mean, not sufficient for dementia diagnosis.
AACD due to changes in connectivity.
Reduciton in cognitive speed and ability as well as memory - primarily due to changes in synpatic density and dendrites and white matter

Question 13

What are the symptoms of Alzheimers?

Answer 13

• Presentation with disturbances of recent memory for 1-3 years.
• Problems with visuospatial function, language and attention.
• Progressive decline in function and increasing frailty.
• 2-4years residential care, survival 3-10years.
• Progressive cognitive decline
• Psychiatric features
Loss of memory
Delusions

Question 14

What are the risk factor’s of Alzheimers?

Answer 14

• Age
• Family History
• APOɛ4 - allele
• Low educational attainment - having a cognitive reserve - increase thickness of grey matter ribbon - as it starts to shrink - take a lot more loss to go through the grey matter
• Cardiovascular disease
• Diabetes Mellitus
• High Serum homocysteine
• Head Injury

Question 15

What is the appearance of the brain of someone with Alzheimer’s?

Answer 15

Reduction of weight
Shriveled and shrunken appearance
Parahippocampal gyrus is dramatically shruneken
Dramatic increase of ventricles
Grey matter ribbon has lost some of its thicknes
senile plaques and neurofibrillary tangles

Question 16

What are senile plaques?

Answer 16

Alzheimer’s
Senile plaques - extracellular - 10% of cortex contains these plaques - 20% of grey matter
Made up of Amyloid beta

Question 17

What is amyloid beta?

Answer 17

40, 42 amino acid protein
Amyloid precursor protein
Chromosome 21 - down’s syndrome
hypothesis cascade?

Question 18

What are neurofibrillary tangles?

Answer 18

Within neurones - fill cell body - extend on apical dendrite
Shape is determined with the cell it is found in
Hypoacitivity of kinases and phosphotases
Tau aggregates in an insoluble form

Question 19

What are the risk factors of stroke?

Answer 19

• Age
• Male gender (MIs)
• Race background (e.g. Asian Indian, African American)
• Family history of stroke
• Prior stroke/ Transient ischaemic attacks
• Vascular disease: hypertension, diabetes, dyslipidaemia
• Asymptomatic carotid atheroma; Atrial Fibrillation
• Alcohol abuse
• Cigarette smoking
• Poor diet
• Physical inactivity

Question 20

What are the symptoms of stroke?

Answer 20

• Paralysis (focal signs) 
• Unilateral disturbance of autonomic 
function (tachycardia, arrhythmia) 
• Aphasia 
• Dizziness or vertigo 
Impairment of vision and balance

Question 21

What are the various causes of intracranial stroke?

Answer 21

• Atherosclerosis (thromboembolic) of arteries (50%) –majority extracranial; few intracranial
• Emboli from circulation (heart) (20%)
• Lacunar infarcts- large or small CNS arteries (~25%)
• Rare causes- vasculitides, bacterial, arterial dissection, etc (5%)

Question 22

What are the causes of hemorrhagic stroke?

Answer 22

20% of all strokes

Causes include hypertension, aneurysms, angiopathy

Question 23

What can cause vascular dementia?

Answer 23

Amyloid deposition
Blood brain barrier leakage
Chronic hyperfusion

Question 24

What are some of the non motor symptoms of Parkinson’s?

Answer 24

Early features - loss of sense of smell, REM sleep behaviour disorder; constipation, depression and anxiety
Late complications - autonomic failure, psychosis and dementia

Question 25

What are the risk factors of Parkinson’s?

Answer 25

• Age
• Family History
• Environmental toxins – E.g. MPTP
• Occupational exposure
• Male gender
• Infection/Inflammation
• Head trauma
• Head Injury
• Patients suffer from resting tremor, rigidity, bradykinesia and postural instability
• Degeneration of dopaminergic neurons in the substantia nigra

Question 26

What are Lewy Bodies?

Answer 26

Within neurons in the cytoplasms,
Alpha synucleun - gradual accumulation - condenses down to form lewy body
look at stages of alzheimers?

Question 27

How can we protect our brains?

Answer 27

• Exercise - increased fitness, increased executive function, reduced GM/WM decline.
• Diet – increased consumption of fish reduced stroke risk (He 2004).
• Antioxidants – protection against cognitive decline.
• Alcohol – some alcohol reduces WML and infarcts (Ruitenbery 2002, Mukamal 2003, Heijer 2004)
‘Cognitive reserve’