Clinical features, assessment and treatments of AD

Question 1

what is dementia

Answer 1

term used to describe a group of related, chronic, organic, brain disorders

• all share a common characteristic
• deterioration in cognitive function leading to a gradual decrease in intellectual capacity

Question 2

what is cognitive decline

Answer 2

a significant decline, from what was normal for an individual, in any of the following:

• consciousness
• memory
• orientation
• concentration and attention
• general knowledge
• intellectual performance
• insight
• judgement
• self awareness

Question 3

describe the prevalence of dementia

Answer 3

most common psychiatric disorder in the community affecting:

• 5% of over 65 years
• 20% of over 80 years

Question 4

what are the classifications of dementia

Answer 4

1. dementia of alzhiemers type early onset
2. dementia of Alzheimers type late onset
   - these 2 represent 50% of all cases
3. vascular dementia
4. Lewy body/parkinsons disease dementia

Question 5

what is the neuropathy of AD

Answer 5

1. generalised cerebral atrophy, especially frontal, parietal and temporal lobes
2. loss of brain volume- by as much as 15% enlargement of sulk and ventricles
3. dramatic loss of central neurones
4. depletion of neurotransmitter levels especially Ach
5. widespread deposition of neurofibrillary tangles and neuritic (senile) plaques

Question 6

what are neurofibrillary tangles (NFTs)

Answer 6

1. remains of defective neurones
2. part of normal ageing, greater number in AD
3. number found on post mortem correlates with duration and severity of AD

Question 7

what are neuritic or senile plaques

Answer 7

1. clumps of dying nerve axons and dendrites

2. appear where neurone loss is most severe

Question 8

what is the neurotransmitter hypothesis

Answer 8

1. cholinergic system critical to normal memory and other cognitive functions
2. selective loss of cholinergic cells from the basal forebrain
3. depletion of neurones in this area correlates with memory and cognitive decline
4. by the time mild symptoms of AD are detectable there is already significant loss of Ach
5. in moderate to severe AD the loss may be as much as 40-90%
6. post mortem reveals significant deficit in synaptosomal Ach plus low levels of acetylcholinesterase and choline acetyltransferase

Question 9

what is the inflammatory hypothesis

Answer 9

1. individuals on long term anti inflammatory therapy have lower incidence of AD
2. initial brain insult leads to neuronal damage and debris deposition
3. cascade process set up leading to neuronal death and propagation of inflammatory response
4. anti inflammatory drugs may help to prevent further propagation of the process
5. NSAIDs not effective in improving AD but may reduce/slow progression from MCI

Question 10

what is the oxidative hypothesis

Answer 10

1. AD due to free radical mediated cell damage

2. oxidative stress leads to tissue inflammation

Question 11

describe the progression and staging of AD

Answer 11

1. early stages (first 3 years)- recent memory impairment, forgetting names, losing direction when out, depression, impaired ADL, language difficulties
2. mid stages (second to tenth year)- amnesia, aphasia, inability to calculate/problem solve, personality changes, behavioural changes, inability to perform ADL
3. late stages (8th to 12th year)- short and long term memory loss, mutism or nonsensical speech, rigid posture, double incontinence, complete dependence on others

Question 12

what is vascular dementia

Answer 12

1. neuronal death brought about by hypoxia or other damage secondary to stroke
2. presents with sudden onset and follows step wise progression
3. frequently history of hypertension, stroke, TIAs
4. no association between choline acetyltransferase level and degree of cognitive decline
5. damage can be focal
6. assessment tools are used to differentiate

Question 13

what is Lewy body dementia

Answer 13

1. progressive dementia, distinguished from AD by fluctuating course and presence fo psychotic symptoms
2. characterised by Parkinsonism symptoms and extreme sensitivity to EPSE from antipsychotics
3. like AD, widespread reduction in choline acetyltransferase
   - also reduction in dopamine
4. Lewy bodies are detectable, intracellular masses, found on post mortem
   - senile plaques may also be present but NFTs are absent
5. Lewy bodies are found in non demented PD patients, but in different brain region to demented PD patients

Question 14

describe the diagnosis of AD

Answer 14

1. diagnosis should only be made when:
   - other general medical conditions have been excluded
   - other psychiatric disorders have been excluded
   - other neurological conditions and reversible causes have been excluded
2. criteria for diagnosis of probable AD
   - dementia established by objective testing
   - deficits in two or more cognitive areas
   - progressive worsening of memory or other cognitive functions
   - no disturbance of consciousness
   - onset between 40-90 years
   - absence of systemic disorders or other neurological disorders

Question 15

what is a mini mental state examination (MMSE)

Answer 15

1. clinical screening tool, tests memory, attention and calculation
2. quick to perform, widely used and understood
3. fairly crude, generally considered insensitive to change, but sensitive to effects of cholinesterase inhibitors
4. each question tests a different aspect of cognition

Question 16

what are the different aspects examined in an MMSE

Answer 16

1. orientation- assesses orientation in time and place
   - disorientation increases as the illness progresses
2. registration- are words understood and can they be repeated
3. attention and concentration- impaired concentration and distractibility common in AD
4. recall and short term memory
5. learning, naming objects and repeating words- may know what an object is but cannot name it (praxis)
6. reading and writing
7. three stage command- patient needs to understand language, remember instructions presented sequentially
8. constructional ability

Question 17

describe the scoring system of MMSE

Answer 17

1. mild AD- MMSE 21-26
2. moderate AD- 10-20
3. moderately severe- 10-14
4. severe- less than 10

Question 18

what is Addenbrookes cognitive examination- ACE-R

Answer 18

1. revised version of a cognitive assessment tool in widespread use
2. this ACE-R incorporates the MMSE

Question 19

what are the advantages of using ACE-R

Answer 19

1. valid in detecting early stages of dementia
2. capable of differentiating sub types
3. good sensitivity and specificity

Question 20

what is sensitivity

Answer 20

relates to the tests ability to identify a condition correctly
sensitivity = number of true positives/ no of true positives + no of false negatives

Question 21

what is specificity

Answer 21

relates to the tests ability to exclude a condition correctly
specificity = no of true negatives/ no of true negatives + no of false positives

Question 22

how is an ACE-R test carried out

Answer 22

1. duration of testing is 12-20 minutes
2. comprises 5 sub scores- each represents one cognitive domain
   - attention/orientation
   - memory
   - fluency
   - language
   - visuospatial
3. using the VLOM ratio, this test can differentiate between AD and frontotemporal dementia, sensitive and specific, and detects early cognitive function

Question 23

describe the treatment strategies

Answer 23

1. augment cholinergic activity
   - inhibit breakdown by cholinesterase- acetylcholinesterase inhibitors
   - AchEIs clinical benefit in AD due to: improve central cholinergic transmission and possible slowing of neuronal degeneration
   - most commonly prescribed: donepezil, rivastigmine, galantamine

Question 24

describe the clinical efficacy of AchEIs

Answer 24

1. all AchEIs statistically significant effect c.f placebo
2. difficult to apply average effects to individual patients
3. average- initial modest improvement, after 9-12 months scores return to baseline level and will then continue to decline
4. 3 groups of responder- non responders, non decliners and improvers
   - variation due to heterogeneity of AD or genetic differences
5. number needed to treat= 3-7

Question 25

describe how AchEIs differ in their precise pharmacology

Answer 25

1. donepezil and galantamine - selective inhibitors of AchE 2. rivastigmine- inhibits AchE and butyrylcholinesterase BuChE 3. Donepezil and rivastigmine- selective for AchE in the brain 4. galantamine- acts on nicotinic receptors, indirect release of Ach

Question 26

give examples of side effects of AchEIs

Answer 26

- nausea/vomiting - dizziness - insomnia - diarrhoea - sweating - can exacerbate peptic ulcer disease, asthma, COPD

Question 27

what is memantine

Answer 27

1. licensed for moderate AD in patients intolerant of or with a contraindication to ACHe inhibitors - and severe AD 2. a voltage dependent, moderate affinity, uncompetitive NMDA receptor antagonist 3. targets glutamate (excitatory amino acid) 4. blocks pathological activation of glutamate receptors without blocking physiological activation (memory function)

Question 28

give examples of side effects of memantine

Answer 28

- hallucinations - confusion - dizziness - headache - somnolence

Question 29

give examples of behavioural and psychological symptoms of dementia- BPSD

Answer 29

1. verbal- complaints, requests for attention, verbal outbursts, shouting, threats, accusations, name calling 2. physical/motor- restlessness, pacing, wandering, fidgeting, incontinence, uncooperativeness 3. other- antisocial behaviour, withdrawal

Question 30

how is BPSD treated

Answer 30

use of antipsychotics (Controversial)

Question 31

what are the potential side effects of using antipsychotics

Answer 31

- falls due to sedation, hypotensive effects, EPSE | - increased risk of strokes

Question 32

what are the 9 key messages in dementia prevention, intervention and care

Answer 32

1. the number of people with dementia is increasing globally 2. be ambitious about prevention- actively treat hypertension in middle aged and older people without dementia - interventions for other risk factors include: more childhood education, exercise, reducing smoking, depression, diabetes and obesity 3. treat cognitive symptoms- should be offered cholinesterase inhibitors at all stages or memantine for severe dementia 4. individualise dementia care- tailored to unique individual needs 5. care for family carers- at high risk of depression 6. plan for future 7. protect people with dementia- risk assessment and management at all stages of the disease is essential but it should be balanced against the persons right to autonomy 8. manage neuropsychiatric symptoms- agitation, low mood 9. consider end of life