39: Neurodegenerative Disorders

Question 1

main characteristics of neurodegenerative disorders

Answer 1

• progressive and irreversible loss of neurons
• due to both genetic and environmental factors
• pathology including cellular aggregation of misfolded prtns

Question 2

loss of hippoampal and cortical neurons results in impaired memory formation and cognitive deficits =

Answer 2

alzheimers disease

Question 3

loss of dopaminergic neurons in basal ganglia leads to altered movement control

Answer 3

parkinson’s disease and huntington’s disease

Question 4

degeneration of cortical and spinal motor neurons results in muscular weakness

Answer 4

amyotrophic lateral sclerosis ALS

Question 5

what prtns accumulate in alzheimers?

Answer 5

b-amyloid plaques and neurofibrillary tangles

Question 6

what prtns accumulate in ALS? parkinson’s disease?

Answer 6

intracytoplasmic aggregrates

parkinsons: alpha-synuclein

Question 7

what prtns accumulate in huntington’s disease?

Answer 7

intranuclear inclusions of huntingin prtn

Question 8

extracellular prion amyloid plaques located in different brain regions =

Answer 8

prion disease (transmissible spongiform encephalopathy TSE)

Question 9

what are the cognitive symptoms of AD?

Answer 9

• loss of short term memory
• aphasia
• apraxia
• agnosia
• disorienation

Question 10

what are the noncognitive symptoms of AD?

Answer 10

• depressioin

- psychotic symptoms

Question 11

initial manifestation of a progressive degenerative dementia

Answer 11

mild cognitive impairment MCI

MCI can progress to AD ata rate of 10-15% per year

not yet dementia

Question 12

language impairment, decreased comprehension, disorientation, and sleep disorders indicate what stage of AD

Answer 12

moderate (2-10 yrs)

Question 13

dependence, delusion, agitation and incapacitation indicate what stage of alzheimers disease?

Answer 13

severe (8-12 yrs)

Question 14

3 pathological signs of AD

Answer 14

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

Question 15

5 brain areas typically affected by AD

Answer 15

hippocampus
nucleus of meynert
temporal lobe
frontal lobe
parietal lobe

Question 16

cholinergic hypothesis

Answer 16

deficiency of Ach causes AD

Question 17

amyloid hypothesis

Answer 17

extracellular accumulations of b-amyloid peptides that are toxic to neurons

but deposition of b-a plaques does not correlate well with neuronal loss

Question 18

why do people with down syndrome experience AD at an early age?

Answer 18

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

Question 19

early onset AD is associated with ___ late onset AD is associated with _____

Answer 19

APP, PSEN1 and PSEN2

E4 allele of APOE (ApoE enhances proteolytic breakdown and clearance of a- within and between cells)

Question 20

50% of all AD patients have this allele

Answer 20

ApoE-E4 isoform for ApoE

Question 21

Tau hypothesis

Answer 21

hyperphosphorylation of Tau aggregates and forms neurofibrilary tangles

tau provides support to microtubules and neuronal cytoskelton

Question 22

first line therapy for symptomatic treatment of cognitive impairments in mild to moderate AD

Answer 22

cholinesterase inhibitors

reduce the breakdown of endogenously released ACh resulting in greater activation of postsynaptic ACh receptors

Question 23

MOA donepezil

Answer 23

inhibits Acetylcholinesterase

Question 24

MOA rivastigmine

Answer 24

inhibits both acetylcholinesterase and butyrylcholinesterase

Question 25

side effects of AchEinibitors

Answer 25

nausea
vomiting
diarrhea
SLUDGE

Question 26

what does SLUDGE stand for?

Answer 26

cholinergic side effects

salivation
lacrimation
urinary incontinence
diarrhea
gastrointestinal cramps
emesis

Question 27

MOA memantine

Answer 27

non-competitive antagonist of the NMDA glutamate receptors with long half-life

provides neuroprotection by reducing intracellular Ca2+ influx and glutamate induced excitotoxicity

Question 28

leading cause of nursing home admission

Answer 28

behavioral and psychiatric symptoms in dementia BPSD

Question 29

treatment for AD associated psychosis/agitated behavior

Answer 29

atypical antipsychotics

risperidone, olanzapine and quetiapine

Question 30

what would you use to treat depression and anxiety in AD? what would you not use?

Answer 30

use SSRI (setraline, citalopram)

do not use TCA (because anticholinergic effects and orthostatic hypotension)

Question 31

what treatments do you avoid for sundowning and wandering?

Answer 31

benzodiazepines

Antihistamines