S4: The Ageing Brain

Question 1

What are the 4 anatomical areas the brain is divided into and their function?

Answer 1

• The cerebrum is the largest part of the brain and alongside the cerebellum is responsible for voluntary actions.
• The cerebellum has a role in coordinating motor control.
• The diencephalon is the midbrain and contains structures such as the thalamus and hypothalamus.
• The brain stem is very important core structure, it is involved in conduction of information from spinal cord to brain, it is the origin of cranial nerves and has cardiorespiratory control and control of level of consciousness.

Question 2

What are the 4 lobes the cerebrum is dived into and their function?

Answer 2

Frontal lobe -> Is involved in executing behaviours, impulsivity and emotion. Parietal lobe -> Sensory processing, reading and writing.
Temporal lobe -> Combines auditory and visual information, memory.
Occipital lobe -> Visual
processing.

Question 3

List brain changes with ageing

Answer 3

~Physical and structural changes:
- Atrophy (it shrinks).
- Ventriculomegaly (size of ventricles increase).
- Neuron loss.
- Increased density of neurofibrillary tangles (aggregates of tau protein due to hyperphosphorylation).
- Oxidative stress and increased inflammation.
- Reduced cerebral blood flow.
~Chemical Changes.
~ Psychological changes.

Question 4

Describe atrophy of the brain with age

Answer 4

• Maximum brain mass is reached around the age of 25 and after this there is gradual loss per year over the next few decades (however this is relatively minimal).
• Once a person hits 50yrs, they start losing more brain mass (0.5% a year) and this rate of loss increases after 70yrs.
• This shrinkage of the brain is regional dependent with some areas of the brain shrinking faster than others. The frontal and temporal lobes shrink at a faster rate but not much atrophy seen in occipital lobe.
• The atrophy is not global as the pre-frontal cortex and striatum most affected and temporal lobe, hippocampus and cerebellum relatively affected.
• As a result there is wider sulci and gyri due to less brain.
• There is also ventriculomegaly.
• Average brain weighs 1.4 kg.

Question 5

Describe neurone loss in brain with age

Answer 5

There are also physical changes seen in our grey and white matter. As a recap grey matter consists of cell bodies and dendrites while white matter consists of mainly myelinated neurones.

• Grey matter starts to decrease once you reach adulthood.
• White matter increases until the age of 40 and then starts to decline. At this point the rate of white matter loss is greater than that of grey matter loss.

Question 6

Describe changes in neurofibrillary tangles and plaques in the brain with age

Answer 6

• Tangles are collections of hyperphosphorlyated tau protein.
• Plaques are deposition of beta amyloid.
• Both are present in ‘normal aging’ but present in larger quantities in ‘abnormal aging’ e.g. Alzheimer’s dementia.
• Hypothesis is that in normal ageing these tangles are found in one location like entorhinal cortex but they don’t spread throughout the brain but in Alzheimer’s these are widespread throughout the brain.
• Plaques in alzheimers are denser.

Question 7

Describe cerebral white matter lesions in the brain

Answer 7

• Cerebral white matter lesions is also known as leukoaraiosis.
• Thought to be due to chronic ischaemic changes over a prolonged period of time and it reduces cerebral blood flow. However, no stroke occurs so no fast loss of deficit in function and loss of brain.
• Associated with vascular risk factors (age related, hypotension related SVD are the most common cause).
• · Possibly related to small vessel strokes of episode of hypoperfusion related to loss of autoregulation.

Question 8

Describe oxidative stress changes to the brain with age

Answer 8

• The brain is unusually sensitive to oxidative stress which is when balance of free radicals and antioxidants is not balanced (more free radicals).
• The free-radical theory of ageing is a big one, with increasing evidence suggesting that accumulation of oxidation of DNA, lipid and protein by free radicals is responsible for the functional decrease in the aged brain.
• With increased free radical damage there is a decline in brain function with inflammatory changes and microvascular changes also present.

Question 9

Describe cerebral blood flow changes with age in the brain

Answer 9

There is about a 5-20% reduction in our cerebral blood flow with age, this evidently affects transport of nutrients and removal of waste products. Couple this with a narrowing of arteries due to atherosclerosis and other changes, this can lead to fluctuant BP and a lack of control over homeostasis of the brain.

Question 10

Describe chemical changes in ageing in brain

Answer 10

The brain also undergoes chemical changes with its neurotransmitters, this change is in the form of a decline in their levels. A decline in the availability and production of acetylcholine, dopamine and serotonin. (largely due to reduction in synthesis, binding sites and the no. of receptors).

• A decline in acetylcholine is associated with cognitive impairment.
• A decline in dopamine is associated with Parkinsonian type symptoms (e.g. reduced arm swing when walking, increased rigidity).
• Decreased serotonin is associated with depression and low mood. It is also associated with changes in circadian rhythm.

Question 11

Describe the neuropsychological changes an ageing brain undergoes

Answer 11

Certain lobes shrink and as a result the function of these areas are affected, functions particularly related to the medial temporal lobes are affected due to being vulnerable to age related change.

• Memory is also impacted but procedural (motor skills), primary and semantic memory (general facts) are well preserved.
• However episodic (memory of events) and working memory (holding and processing) and executive function (planning and managing tasks) are most affected and a decline is seen in these.
• Reduced: New memory learning, problem solving, verbal fluency, completion of visuo-spatial tasks.
• Preservation: Remote memory and vocabulary and comprehension.

Question 12

Describe changes seen in BBB with age

Answer 12

We start to see an altered transport of nutrients, metabolites and toxins to the brain. This is due to increased permeability and reduced transport of glucose, proteins and hormones. Thus the elderly are more susceptible to hypoglycaemia.

Question 13

Combined changes to ageing brain (physical, chemical, psychological)

Answer 13

• Difficulty in learning new things.
• Difficulty in retrieving information.
• Slower processing speed.
• Problem solving ability declines.
• Reasoning about things that are unfamiliar decline.
• Attending to and manipulating their own environment can be more difficult (e.g. looking after garden is now harder).

Question 14

What is delirium?

Answer 14

Delirium is NOT dementia, rather it is defined as being an acute confusional state that is characterized by disturbed consciousness, cognitive function or perception that has an acute onset and a fluctuating course.

• ANYONE can get delirium but it is more common with advancing age. Mean age is 75-82 years old.
• Prevalence varies widely and 10-40% among hospitalized older adults.
• Mortality can be as high as 50% in delirium and it is common, half of people with hip fractures will suffer an episode of delirium. However, delirium is treatable.

Question 15

Risk factors for delirium

Answer 15

• They are older than 65.
• Have fractured the neck of the femur (hip).
• Have a severe illness.
• Suffer from dementia.

Question 16

How does cognitive reserve affect dementia?

Answer 16

There is a level we will all get dementia or delirium but higher cognitive reserve protects us from these to some extent (so slower deterioration) e.g. Uni increases cognitive research (start from higher cognitive level). There are ‘hits’ we can take that decrease our cognitive reserve e.g. hip fracture. The cognitive reserve in the brain does not fully recover but it still recovers to some extent,

Question 17

Indicators and practical signs of delirium

Answer 17

Indicators (fluctuations or changes in an individuals):
- Cognitive function.
- Perception.
- Physical function.
- Social behaviour.
- Often worst in the evening (sun-downing).
Practical signs:
- Just “more confused”.
- Poor attention- can’t give a history.
- Looks around the room.
- Agitated, plucking at bed clothes.
- Hallucinating.
- Very quiet or drowsy.
- Reduced ability to care for self.
- Loss of mobility.

Question 18

Types of delirum

Answer 18

1. It can be hyperactive delirium where an individual is moving about interacting and communicating.
2. There is hypoactive delirium where the individual seems depressed and don’t want to engage.
3. There is also a mixed delirium that has components of both.

Question 19

Compare hyperactive delirium and hypoactive delirium

Answer 19

Hyperactive delirium:
- Increased motor activity.
- Loss of control of activity.
- Restlessness.
- Wandering.
Hypoactive delirium:
- Decreased activity.
- Decreased action speed.
- Decreased speed and amount of speech.
- Reduced awareness of surroundings.
- Listlessness.
- Withdrawal.
Hypoactive delirium is most common and has the worst outcome due to it not being diagnosed as much (mistaken for depression or dementia) and not as troublesome so less attention payed to them (more easy to look after than hyperactive) and is 50% of delirium! Hyperactive makes up only about 20%.

Question 20

How to assess delirium?

Answer 20

• History and examination can be difficult.
• NEED collateral (Speak Gp, next of kin etc it cant get info out of patient).
• Cognitive Screening tests: 4AT, Abbreviated Mental Test Score, Montreal Cognitive Assessment.
• Basic Investigations.

Question 21

Describe 4AT

Answer 21

1. Alertness is measured, are they awake, agitated or drowsy while talking to you?
   2.AMT, do they know their age, their DOB, where they are and what year it is?
2. Their attention and concentration, in this test naming months of year backwards?
3. Has there been an acute change or fluctuation in patients mental state in recently?
   - With regards to the scoring system:
   A score of 4 or more = possible delirium with or without cog. Impairment.
   A score of 1 – 3 = possible cognitive impairment.
   A score of 0 = delirium or cognitive impairment unlikely.

Question 22

Describe Abbreviated mental test (AMT)

Answer 22

1. Age.
2. Time.
3. Address for recall at end of test.
4. Year.
5. Name of this place.
6. Identification of two people e.g. nurse, doctor.
7. Date of birth.
8. Year of first world war.
9. Name of present monarch.
10. Count backwards 20 to 1 and address recall.

Question 23

Mechanism of Delirium

Answer 23

• Reduction in Ach and increase in dopamine. Theory that mediated by: acute stress response
• Increased cortisol.
• Increased sympathetic activation.
• Elevated cytokines. Because BBB in older people isn’t as selective in older people the increase causes neuronal dysregulation and inflammation.
• Often multifactorial cause for delirium.
• Cognitive reserve.

Question 24

Causes of delrium

Answer 24

• Infection.
• Urinary retention.
• Constipation.
• Pain.
• Cardioresp problems.
• Metabolic/homeostatic problems: Dehydration, Hypo or Hyperglycaemia, Electrolyte disturbance, High Ca/High Na/Low Na, Hypo or Hyperthyroidism, Hypoxia, Thiamine Deficiency.
• Neuro problems: Non convulsive status (hypoactive delirium as brain is having massive electricity firing), Subdural haematomas, Stroke, Auto-immune encephalitis.
• Medication: Benzodiazepines, Anticholinergics e.g. TCA’s, Opioids, Anti-Parkinson’s drugs, Drug or Alcohol withdrawal.
• Drugs, alcohol, nicotine withdrawal, surgery/general anaesthesia.
• Environmental factors: Change of environment, Sleep deprivation, Invasive lines or investigations, Physical restraint.

Question 25

Investigation for delirium

Answer 25

Often to look for causes as no clinical test for delirium. Diagnosis based on symptoms and examination.

Question 26

Consequences of delirium

Answer 26

Delirium also has negative consequences as well as being an unpleasant, pathological episode. Delirium is associated with an:

• Increased length of stay in hospital.
• Increased risk of dementia.
• Increased hospital acquired complications (e.g. bacteremia).
• An increased risk of having a need of long term care later on in life.
• Increased mortality.
• Increased cost, hospital admission stay for delirium is £13,000!
• Pressure sores.

Question 27

Differential Delirium, Dementia and Depression

Answer 27

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