Alzheimer's

Question 1

definition of dementia

Answer 1

progressive clinical syndrome where the deterioration of mental function is significant enough to interfere with activities of daily living

Question 2

criteria for the diagnosis of dementia to be make ;

Answer 2

patient must have;

1. impairment in atleast two cognitive domains such as ; memory, thinking, language, orientation + judgement
   - leading to significant functional decline enough to effect activities of daily living

• cannot be explained by
  another disorder or adverse effects of medication

Question 3

Pathophysiology of Alzheimer’s disease

Answer 3

• most common cause of dementia

1. Development of plaques
   - amyloid precursor proteins are proteins which help neurons grow and repair
   - beta amyloid plaques are fragments of amyloid precursor proteins
   - beta amyloid plaques can break off and form clumps of protein plaques which can interrupt signals between neurons
2. reduction in acetylecholine production -> memory loss
3. Amyloid deposits in blood vessels walls - accumulate and weaken the vessels increasing risks of hemorrhaging
4. Trigger neurofibrillary tangles - accumulate within the nrurons and this prevents effective signally which can lead to apoptosis

Question 4

clinical features of Alzheimer’s

Answer 4

1. generalised atrophy of the brain
2. Gyrie become narrower
3. Sulci get wider
4. Ventricles get larger

Question 5

Risk factors

Answer 5

Down’s

Question 6

Early onset Alzheimer’s ( < 65 )

Answer 6

Has a very strong genetic link

1. Amyloid precursor protein on chromosome 21
   - adults with down’s syndrome (trisomy 21) likely to develop Alzheimer’s due to triplication of chromsome 21
   - as there is over expression of gene for amyloid precursor protein
2. Presenilin 1 and 2 (PSEN 1 or PSEN 2)
   - PSEN 1 on chromosome 14 and PSEN 2 on chromosome 1
3. These genes virtually guarantee that the indivisual will develop Alzheimer’s disease

Question 7

Environmental factors contributing to Alzheimer’s disease

Answer 7

1. Aluminium in Alzheimer’s disease in dialysis patients
2. low social class + nutrition
3. HRT - a protective factor

Question 8

Macroscopic changes seen in Alzheimer’s

Answer 8

widespread cerebral atrophy, particularly involving the cortex and hippocampus

Question 9

non pharmacological management of Alzheimer’s

Answer 9

NICE recommend;
1. offering ‘a range of activities to promote wellbeing that are tailored to the person’s preference’

2. offering group cognitive stimulation therapy for patients with mild and moderate dementia
3. other options to consider include group reminiscence therapy and cognitive rehabilitation

Question 10

First line pharmacological management of Alzheimer’s

Answer 10

Three acetylcholinesterase inhibitors;
-  donepezil
- galantamine
- rivastigmine
as options for managing mild to moderate Alzheimer's disease

Question 11

Second line pharmacological management of Alzheimer’s

Answer 11

memantine (an NMDA receptor antagonist) is in simple terms the ‘second-line’ treatment for Alzheimer’s,

NICE recommend it is used in the following situation reserved for patients with

→ moderate Alzheimer’s who are intolerant of, or have a contraindication to, acetylcholinesterase inhibitors

→ as an add-on drug to acetylcholinesterase inhibitors for patients with moderate or severe Alzheimer’s

→ monotherapy in severe Alzheimer’s

Question 12

Managing non cognitive symptoms of Alzheimer’s

Answer 12

1. NICE does not recommend antidepressants for mild to moderate depression in patients with dementia
2. antipsychotics should only be used for patients at risk of harming themselves or others, or when the agitation, hallucinations or delusions are causing them severe distress

Question 13

What are neurofibrillary tangles?

Answer 13

4. Neurofibrillary tangles
   paired helical filaments are partly made from a protein called tau

in AD are tau proteins are excessively phosphorylate

Question 14

Microscopic changes seen;

Answer 14

1. cortical plaques due to
   - deposition of type A-Beta-amyloid protein
   - intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein

Question 15

What is there a deficiency of?

Answer 15

deficit of acetylcholine from damage to an ascending forebrain projection