Alzheimer's

Question 1

What is the role of the hippocampus

Answer 1

lobe) involved in memory. Also, in spatial navigation. Left hemisphere is verbal memory. Right hemisphere is visual memory.

Question 2

What is the anatomy of cognitive failure

Answer 2

Pattern of cognitive failure is linked to distribution of brain and neurotransmitter dysfunction in early stages
Regional and global brain atrophy occurs in alter stages
Medial temporal atrophy = hippocampal atrophy - memory deficit

Question 3

How many people over 65 have dementia

Answer 3

1 in 14

Question 4

What is aphasia

Answer 4

understand and production of language. Uses simpler language, less use of abstract and descriptive terms, word finding problems, naming difficulties, receptive problems. Finally, complete loss of communication

Question 5

What is apraxia

Answer 5

inability to preform volitional acts despite intact motor and sensory systems such as dressing, eating, constructional (e.g. drawing a clock), ideomotor (waving goodbye)

Question 6

What is agnosia

Answer 6

inability to understand the significance of sensory stimuli.

Question 7

What is MMSE

Answer 7

Mini mental state examination (out of 30) - cut off for dementia differs from individual to individual. 24 is mild, 20 is moderate, 10 is severe (guideline)

Question 8

WHat is ACE-R

Answer 8

Addenbrooke’s) out of 100: tests more frontal lobe domains. Below 80, indictive of dementia.
Only first year can drugs make improvement

Question 9

What are the neuropsychiatric symptoms of dementia

Answer 9

Neuropsychiatric symptoms: hallucinations (visual most common), delusion (false belief, typically of theft), depression, apathy, behavioural disturbance, eating preference (sweet remains longest), disinhibition (sometimes sexual), sleep behaviours (loss of sense of time)

Question 10

What are the signs with vascular dementia

Answer 10

Vascular (problem with atherosclerosis): Stepwise deterioration in cognitive function, often coexists with Alzheimer’s, vascular risk factors, neurological symptoms (mild/subtle). Will stable for longer than Alzheimer’s

Question 11

What are the signs of Alzeheimer’s

Answer 11

gradual onset, memory involved early, progressive cognitive decline

Question 12

What are the signs for dementia with lewy bodies

Answer 12

day to day fluctuation in cognition. Visual hallucinations. Sleep disturbance (REM sleep behaviour disorder). Parkinsonism. Fall/syncope

Question 13

What are the signs for fronto-temporal dementia

Answer 13

early decline in social/personal conduct. Different variants affecting behaviour and language. Memory preserved in early stages

Question 14

What is the cholinergic hypothesis for AD

Answer 14

several cholinergic markers are reduced in AD>. Cholinergic pathways are widely distributed throughout the CNS. Central cholinergic transmission is involved with cognition, attention, memory, and reflex visceral control.

Question 15

How do amyloid plaques affect Alzheimer’s

Answer 15

cerebellum also spared. Beta-amyloid peptides are derived from beta-amyloid precursor protein. Represents a type 1 transmembrane receptor protein. APP cleaved in extracellular region by BACE1 and then cleaved again by gamma-secretase. Amyloid deposits occur earlier than tau tangles. A mutation at codon 717 of beta-amyloid precursor gene increases production beta amyloid -> amyloid cascade hypothesis.
Hypothesis: increase in beta-amyloid increase tau->dementia

Question 16

What are neurofibrillary tangles

Answer 16

made from tau. Promotes microtubule formation. Tau has many potential phosphorylation sites and 6 major splice variants. After hyper-phosphorylation, tau can no longer bind to microtubules and will aggregate. Aggregate form paired helical filaments, then these filaments aggregate to form neurofibrillary tangles. Tangles start in brainstem, spreads temporal cortex and then frontal cortex. Cerebellum spared.
Plaques are much bigger

Question 17

What happens to the cortex and hippocampus in AD

Answer 17

Cortex shrivels up, damaging areas involved in thinking, planning, and remembering. Ventricles filled with cerebrospinal fluid grow larger. Hippocampus shrinks severely.

Question 18

What causes early onset AD

Answer 18

autosomal dominant or familial form. Only accounts for 5% of cases. Due to point mutations in APP (40-50), PSEN1 (30-40), and PSEN2 (50-60). PSEN part of gamma secretase complex, which plays an important role in generation of amyloid beta from APP.

Question 19

What causes late onset AD

Answer 19

Late onset: most common, over 60 years of age. Sporadic form. Late onset also has a strong genetic component. Strongest genetic risk is APOE, e4 allele. However, e4 allele means lower risk of CHD.

Question 20

What is lost first in AD

Answer 20

Synapse loss is one of the earliest events and the most important AD pathology. No real mechanism known.

Question 21

What cholinesterase inhibitors are used

Answer 21

Donepezil, galantamine, and rivastigmine

Question 22

What do cholinesterase inhibitors do

Answer 22

Inhibits breakdown of ACh, prolonging presence of neurotransmitter at synapses
Temporary symptomatic relief. At best, delays progression by 1 year

Question 23

What NMDA receptor antagonists are used

Answer 23

Memantine

Question 24

What does memantine do

Answer 24

Blocks glutamate binding to NMDA receptors. There is an increase in activation of extra-synaptic NMDA receptors in AD pathogenies - results in the activation of cell death pathway. Therefore, antagonising NMDA receptors would block exocytotic effects - may also block NMDA receptor mediated hyperphosphorylation of tau