Alzheimer's Flashcards
What is the role of the hippocampus
lobe) involved in memory. Also, in spatial navigation. Left hemisphere is verbal memory. Right hemisphere is visual memory.
What is the anatomy of cognitive failure
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
How many people over 65 have dementia
1 in 14
What is aphasia
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
What is apraxia
inability to preform volitional acts despite intact motor and sensory systems such as dressing, eating, constructional (e.g. drawing a clock), ideomotor (waving goodbye)
What is agnosia
inability to understand the significance of sensory stimuli.
What is MMSE
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)
WHat is ACE-R
Addenbrooke’s) out of 100: tests more frontal lobe domains. Below 80, indictive of dementia.
Only first year can drugs make improvement
What are the neuropsychiatric symptoms of dementia
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)
What are the signs with vascular dementia
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
What are the signs of Alzeheimer’s
gradual onset, memory involved early, progressive cognitive decline
What are the signs for dementia with lewy bodies
day to day fluctuation in cognition. Visual hallucinations. Sleep disturbance (REM sleep behaviour disorder). Parkinsonism. Fall/syncope
What are the signs for fronto-temporal dementia
early decline in social/personal conduct. Different variants affecting behaviour and language. Memory preserved in early stages
What is the cholinergic hypothesis for AD
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.
How do amyloid plaques affect Alzheimer’s
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
What are neurofibrillary tangles
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
What happens to the cortex and hippocampus in AD
Cortex shrivels up, damaging areas involved in thinking, planning, and remembering. Ventricles filled with cerebrospinal fluid grow larger. Hippocampus shrinks severely.
What causes early onset AD
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.
What causes late onset AD
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.
What is lost first in AD
Synapse loss is one of the earliest events and the most important AD pathology. No real mechanism known.
What cholinesterase inhibitors are used
Donepezil, galantamine, and rivastigmine
What do cholinesterase inhibitors do
Inhibits breakdown of ACh, prolonging presence of neurotransmitter at synapses
Temporary symptomatic relief. At best, delays progression by 1 year
What NMDA receptor antagonists are used
Memantine
What does memantine do
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
