Flashcards in 39: Neurodegenerative Disorders Deck (31):
main characteristics of neurodegenerative disorders
- progressive and irreversible loss of neurons
- due to both genetic and environmental factors
- pathology including cellular aggregation of misfolded prtns
loss of hippoampal and cortical neurons results in impaired memory formation and cognitive deficits =
loss of dopaminergic neurons in basal ganglia leads to altered movement control
parkinson's disease and huntington's disease
degeneration of cortical and spinal motor neurons results in muscular weakness
amyotrophic lateral sclerosis ALS
what prtns accumulate in alzheimers?
b-amyloid plaques and neurofibrillary tangles
what prtns accumulate in ALS? parkinson's disease?
what prtns accumulate in huntington's disease?
intranuclear inclusions of huntingin prtn
extracellular prion amyloid plaques located in different brain regions =
prion disease (transmissible spongiform encephalopathy TSE)
what are the cognitive symptoms of AD?
-loss of short term memory
what are the noncognitive symptoms of AD?
initial manifestation of a progressive degenerative dementia
mild cognitive impairment MCI
MCI can progress to AD ata rate of 10-15% per year
not yet dementia
language impairment, decreased comprehension, disorientation, and sleep disorders indicate what stage of AD
moderate (2-10 yrs)
dependence, delusion, agitation and incapacitation indicate what stage of alzheimers disease?
severe (8-12 yrs)
3 pathological signs of AD
1. neuronal degeneration and cortical atrophy
2. neuritic plaques (amyloid or senile)
3. neurofibrillary tangles
these changes eventually lead to clinical symptoms, but they begin years before the onset of symptoms
5 brain areas typically affected by AD
nucleus of meynert
deficiency of Ach causes AD
extracellular accumulations of b-amyloid peptides that are toxic to neurons
but deposition of b-a plaques does not correlate well with neuronal loss
why do people with down syndrome experience AD at an early age?
APP gene is on chromosome 21, people with trisomy 21 (down syndrome) have extra copies of APP and commonly exhibit AD by age of 40
early onset AD is associated with ___ late onset AD is associated with _____
APP, PSEN1 and PSEN2
E4 allele of APOE (ApoE enhances proteolytic breakdown and clearance of a- within and between cells)
50% of all AD patients have this allele
ApoE-E4 isoform for ApoE
hyperphosphorylation of Tau aggregates and forms neurofibrilary tangles
tau provides support to microtubules and neuronal cytoskelton
first line therapy for symptomatic treatment of cognitive impairments in mild to moderate AD
reduce the breakdown of endogenously released ACh resulting in greater activation of postsynaptic ACh receptors
inhibits both acetylcholinesterase and butyrylcholinesterase
side effects of AchEinibitors
what does SLUDGE stand for?
cholinergic side effects
non-competitive antagonist of the NMDA glutamate receptors with long half-life
provides neuroprotection by reducing intracellular Ca2+ influx and glutamate induced excitotoxicity
leading cause of nursing home admission
behavioral and psychiatric symptoms in dementia BPSD
treatment for AD associated psychosis/agitated behavior
(risperidone, olanzapine and quetiapine)
what would you use to treat depression and anxiety in AD? what would you not use?
use SSRI (setraline, citalopram)
do not use TCA (because anticholinergic effects and orthostatic hypotension)