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3922 > 19 - Alzheimer's / Cognitive Enhancers > Flashcards

19 - Alzheimer's / Cognitive Enhancers Flashcards

1
Q

What are some treatable dementias (8)

A
  1. General paresis
  2. Normal pressure hydrocephalus
  3. Chronic subdural haematoma
  4. Nutritional deficiencies
  5. Chronic drug intoxication
  6. Endocrine-metabolic disorders
  7. Brain tumours
  8. Psuedodementia
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2
Q

What are some degenerative dementias (7)

A
  1. Alzheimer’s Disease
  2. Dementia with Lewy bodies
  3. Vascular dementia
  4. Frontotemporal dementias
  5. Prion disease
  6. Huntington’s disease
  7. Thalamic dementia
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3
Q

What are the clinical features of AD

A
  1. Initially subtle changes in memory and cognition
  2. Changes in spatial and temporal orientation
  3. Difficulty forming new memories
  4. Altered judgement
  5. Eventually institutionalisation
  6. Overt parkinsonism
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4
Q

What are some of the later symptoms of AD

A
  1. Dysphasia (speech)
  2. Apraxia (move)
  3. Agnosia (loss of knowledge)
  4. Paranoia, psychosis
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5
Q

What are the 4 pathological features of AD

A
  1. Cerebral atrophy and ventricular enlargement
  2. Neuronal loss with gliosis
  3. Amyloid plaques
  4. Neurofibrillary tangles
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6
Q

What is the main protein in amyloid plaques

A

AB peptide

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7
Q

What are amyloid plaques derived from

A

Amyloid precursor protein (APP)

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8
Q

What are neurofibrillary tangles

A

Abnormal bunches of filaments within neurons

Hyperphosphorylated tau protein

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9
Q

What are 4 things of acetylcholine transmission that is affected in AD

A

1) Loss of cells in nucleus basalis
2) Decreased choline acetyltransferase
3) Acetylcholine esterase
4) Choline uptake

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10
Q

What are two aspects of amine transmission affected in AD

A

1) Loss of cells in locus coeruleus (decreased NA synthesis)

2) Loss of cells on raphe nuclei (decreased 5HT synthesis)

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11
Q

What are two aspects of glutamate transmission affected in AD

A

1) Reduction in glutamate transporters (?)

2) Induce excitoxicity

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12
Q

What is the 1st line drug for AD

A

Cholinesterase inhibitors

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13
Q

How are antidepressants and neuroleptics used in AD

A

1) Modulate NA and 5-HT neurotransmission

2) Improve emotional state, do not affect core symptoms

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14
Q

What genes contribute to the Amyloid Precursor Protein

A

Chromosome 21

Down’s Syndrome

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15
Q

What genes contribute to the formation of presenilins 1 and 2

A

Chromosomes 1, 14

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16
Q

What does apoE determine

A

Age of onset in AD.
e4 allele 80 onset
e2 allele 90 onset

17
Q

How many AD cases are sporadic

A

> 95%

18
Q

What is y-secretase

A

Complex of presenilin, nicastrin, APH1 and presenilin enhancer 2

19
Q

How is y-secretase activated

A

Cleavage of presenilin to expose the asp-asp catalytic site

20
Q

What drugs can disrupt y-secretase activity

A

Peptide based inhibitors binding to catalytic site

NSAIDs

21
Q

Which ApoE is protective which one increases risk

A

ApoE2 is protective

ApoE4 increases risk/early onset

22
Q

What may disrupt processing of APP

A

Elevated cholesterol

Statins may help reduce incidence

23
Q

What metals promote the formation of amyloid plaques

A

Zinc and chopper

24
Q

What two drugs help to chelate metals to reduce plaque formation

A

Clioquinal anitbiotic

Lipoic acid

25
Q

What is immunotherapy for AD

A

Immunisation with B-amyloid

26
Q

What are nootropics

A

Drugs which have the ability to enhance integrative brain mechanisms associated with mental performance

27
Q

What are some features of nootropics

A

Ability to enhance learning and memory
Facilitate flow of information between hemispheres
Enhance resistance to chemical or physical assault
Lack of peripheral, sedative or neuroleptic effects

28
Q

What are some nootropics

A

Piracetam

Pramiracetam

29
Q

What do nootropics do

A

Enhance release of ACh

Cognitive enhancement in rats

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