Lecture 38: Memory, Alzheimer's disease

Question 1

Ageing and memory?

Answer 1

In almost all populations there is:

1. Increased variability between individuals
2. reduced speed of processing, some reduction in attention, divided-switching attention
3. Reduced working memory (eg. not as many ph. numbers)
4. Reduced retrieval of episodic (factual, time, date, where) and to a lesser extent sematic memory (you know it but just can’t remember what - what was for dinner last night)

Question 2

Dementia?

Answer 2

• A sign symptom complex or description - NOT a diagnosis
• “Brain failure”
• A chronic or persistant disorder of the mental process caused by brain disease or injury and marked memory, personality and reasoning changes
• Severe enough to interfere with normal activities (exclude delirium and depression etc.)
• Delirium is relatively acute unlike dementia

Question 3

Observable differences in a brain with Alsheimer’s disease?

Answer 3

The brain tissue as a whole shrinks and the ventricles begins to take up more space.

CT or usually more helpful MRI are used to have a look at the brain

This image shows a histological slice enhanced to show losses of brain tissue in an AD brain

Question 4

SDAT?

Answer 4

Senile dementia of the Alheimer’s type

The most commone type of dementia, with gradual progressive dementia not explained by other known factors

Question 5

Pathology of SDAT?

Answer 5

Key characteristics are:

1. Extensive and progressive loss of neurons
2. Histological findings of neurofibrillary tangles and plaques
3. Widespread atrophy with shrinking of gyri and hippocampus as well as widening and enlarging of sulci and ventricles respectively

Question 6

Neurofibrillary tangles and plaque features?

Answer 6

Neurofibrillary tangles

• Found in great conc within the neurons in SDAT particularly in the cortex and hippocampus
• Very rarely found in normally ageing brains

Plaques

• extracellular plaques are a defining feature of SDAT
• composed of P-amyloid and termed “senile plaques” they are found in SDAT irrespective of age BUT, also in some normally aged people.
• May be a cause of neurodegenerative disease but also may be a product of it.

Question 7

Basis of treatment?

Answer 7

There is no treatment for the disease. The treatment is symptomatic only.

Question 8

Symptomatic treatment?

Answer 8

Mostly based around reversing the cholinergic deficit. Presynaptic, synapse or postsynaptic targets. Although this shows limited benefit - 4/10 people show moderate benefit for about 6-12months keeping them where they are at.

Question 9

Potential way to block plaque formation?

Answer 9

By cutting out B-secretase would theoretically stop some production of B-Amyloid and hence plaques. None of them have come out with much success especially as it is often too little too late. (but then everyone have amyloid in their brain)

Through marking amyloid and setting up an immune reaction to remove the amyoild through passive immunisation. BUT, in humans there were too many autoimmune reactions.