19 - Alzheimer's / Cognitive Enhancers Flashcards
What are some treatable dementias (8)
- General paresis
- Normal pressure hydrocephalus
- Chronic subdural haematoma
- Nutritional deficiencies
- Chronic drug intoxication
- Endocrine-metabolic disorders
- Brain tumours
- Psuedodementia
What are some degenerative dementias (7)
- Alzheimer’s Disease
- Dementia with Lewy bodies
- Vascular dementia
- Frontotemporal dementias
- Prion disease
- Huntington’s disease
- Thalamic dementia
What are the clinical features of AD
- Initially subtle changes in memory and cognition
- Changes in spatial and temporal orientation
- Difficulty forming new memories
- Altered judgement
- Eventually institutionalisation
- Overt parkinsonism
What are some of the later symptoms of AD
- Dysphasia (speech)
- Apraxia (move)
- Agnosia (loss of knowledge)
- Paranoia, psychosis
What are the 4 pathological features of AD
- Cerebral atrophy and ventricular enlargement
- Neuronal loss with gliosis
- Amyloid plaques
- Neurofibrillary tangles
What is the main protein in amyloid plaques
AB peptide
What are amyloid plaques derived from
Amyloid precursor protein (APP)
What are neurofibrillary tangles
Abnormal bunches of filaments within neurons
Hyperphosphorylated tau protein
What are 4 things of acetylcholine transmission that is affected in AD
1) Loss of cells in nucleus basalis
2) Decreased choline acetyltransferase
3) Acetylcholine esterase
4) Choline uptake
What are two aspects of amine transmission affected in AD
1) Loss of cells in locus coeruleus (decreased NA synthesis)
2) Loss of cells on raphe nuclei (decreased 5HT synthesis)
What are two aspects of glutamate transmission affected in AD
1) Reduction in glutamate transporters (?)
2) Induce excitoxicity
What is the 1st line drug for AD
Cholinesterase inhibitors
How are antidepressants and neuroleptics used in AD
1) Modulate NA and 5-HT neurotransmission
2) Improve emotional state, do not affect core symptoms
What genes contribute to the Amyloid Precursor Protein
Chromosome 21
Down’s Syndrome
What genes contribute to the formation of presenilins 1 and 2
Chromosomes 1, 14
What does apoE determine
Age of onset in AD.
e4 allele 80 onset
e2 allele 90 onset
How many AD cases are sporadic
> 95%
What is y-secretase
Complex of presenilin, nicastrin, APH1 and presenilin enhancer 2
How is y-secretase activated
Cleavage of presenilin to expose the asp-asp catalytic site
What drugs can disrupt y-secretase activity
Peptide based inhibitors binding to catalytic site
NSAIDs
Which ApoE is protective which one increases risk
ApoE2 is protective
ApoE4 increases risk/early onset
What may disrupt processing of APP
Elevated cholesterol
Statins may help reduce incidence
What metals promote the formation of amyloid plaques
Zinc and chopper
What two drugs help to chelate metals to reduce plaque formation
Clioquinal anitbiotic
Lipoic acid
