Unit 3 Neurodegenerative

Question 1

Neurodegenerative Disorders main characteristics

Answer 1

progressive & irreversible loss of neurons from brain regions, injury of specific type of neurons & locations, due to both genetic & environmental factors, pathology includes cellular aggregation of misfolded proteins

Question 2

Alzheimer’s Disease

Answer 2

loss of hippocampal & cortical neurons results in impaired memory formation & cognitive deficits

Question 3

Parkinson’s disease & Huntington’s disease

Answer 3

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

Question 4

Amyotrophic Lateral Sclerosis (ALS)

Answer 4

Degeneration of control & spinal motor neurons results in muscular weakness

Question 5

Alzheimer’s protein accumulation

Answer 5

extracellular beta-amyloid plaques & intracytoplasmic neurofibrillary tangles (tau protein)

Question 6

ALS & Parkinson’s protein accumulation

Answer 6

Intracytoplasmic aggregates

Parkinson’s = alpha synuclein

Question 7

Huntington’s protein accumulation

Answer 7

Intranuclear inclusions of huntingtin protein

Question 8

Prion disease protein accumulation

Answer 8

extracellular prion amyloid plaques in different brain regions

Question 9

Neurodegenerative disorders occur at what stage in life

Answer 9

later - over age of 65

Question 10

Alzheimer’s cognitive symptoms

Answer 10

Loss of short-term memory, Aphasia, Apraxia, Agnosia, Disorientation

Question 11

Alzheimer’s noncognitive symptoms

Answer 11

Depression, psychotic symptoms, behavioral disturbances

Question 12

Alzheimer’s diagnosis

Answer 12

Based on clinical assessment - requires dementia (cognitive impairments beyond normal for their age)
Neuroimaging (CT & MRI)
Mild cognitive impairment (MCI) - initial diagnosis/manifestation of disease

Question 13

MCI (mild cognitive impairment)

Answer 13

Can progress to Alzheimer’s but doesn’t always
Initial manifestation of progressive degeneration dementia
Cognitive impairment not reducing function (prefrontal cortex may be effected)

Question 14

Most common cause of dementia in people 65 yrs or older

Answer 14

Alzheimer’s disease

Question 15

Patients usually die within _____ of AD onset

Answer 15

6-12 years

Question 16

Mild stage AD

Answer 16

First 3 years
Progressive loss of memory, impaired judgement, confusion, decreased concentration
Areas of brain effected are increasing

Question 17

Moderate stage AD

Answer 17

2-10 years
Language impairments, decreased comprehension, sleep disorders, disorientation
Requires increase level of care

Question 18

Severe stage AD

Answer 18

8-12 years
Most of brain affected, large amount of atrophy
Dependence, delusions, agitation, incapacitation (noncognitive disorders as well)
Needs to be in a care facility

Question 19

Pathology of AD

Answer 19

Massive tissue damage & decreased brain volume from neuronal degeneration & atrophy, neuritic plaques, & neurofibrillary tangles

Question 20

Cholinergic hypothesis of AD

Answer 20

Deficiency of ACh in certain brain areas due to degeneration of subcortical cholinergic neurons in hippocampus

Question 21

Amyloid hypothesis of AD

Answer 21

Extracellular accumulations of beta-amyloid peptides that are toxic to neurons
Cleaved from APP & produced faster than cleared

Question 22

Early-onset AD

Answer 22

Rare, related to mutations in APP & PSEN1/2 (cleave APP)

Overproduction of beta-amyloid

Question 23

Late-onset AD

Answer 23

Common, epsilon4 allele of APOE - not as effective at clearing beta-amyloid
increases risk of AD 3x

Question 24

Tau hypothesis of AD

Answer 24

Hyperphosphorylation of tau causes aggregates & forms neurofibrillary tangles
Causes microtubular instability, collapse of transport system, altered NT release & synaptic function, and cell death

Question 25

AD treatment goals

Answer 25

Slow down progression, treat cognitive difficulties & preserve function, treat behavioral & psychiatric symptoms

Question 26

Cholinesterase inhibitors used for

Answer 26

First line for symptomatic treatment of cognitive impairments in mild to moderate AD Slows decline of cognitive & behavioral function

Question 27

Cholinesterase inhibitors MOA

Answer 27

block AChE &/or BChE-mdiated breakdown of ACh to choline & acetate Increase activation of postsynaptic ACh receptor

Question 28

Cholinesterase inhibitors include

Answer 28

Tacrine, Donepezil, Rivastigmine, Galantamine

Question 29

Tacrine

Answer 29

Cholinesterase inhibitor | No longer used - had extensive side effects & needed to be taken 4x per day (short 1/2 life) = bad compliance

Question 30

Donepezil

Answer 30

Cholinesterase inhibitor Primarily inhibits AChE Long 1/2 life - once day dose Improve cognition & clinical function, delay symptomatic progression

Question 31

Rivastigmine

Answer 31

Cholinesterase inhibitor Inhibits both AChE & BChE 2x per day dose Transdermal patch can be used - has improved GI effects

Question 32

Galantamine

Answer 32

Cholinesterase inhibitor similar to Donepezil & Rivastigmine 2x per day dose Main side-effects GI

Question 33

Cholinesterase inhibitors side effects

Answer 33

GI effects main problem (nausea, vomiting, diarrhea) Other side effects related to ACh: salivation, sweating, urinary incontinence, dizziness, muscle weakness, bradycardia SLUDGE

Question 34

Memantine

Answer 34

Glutamate antagonist Non-competitive antagonist of NMDA glutamate receptor Neuroprotection by reducing intracellular Ca influx & glutamate induced excitotoxicity long 1/2 life Commonly used in moderate-severe AD Often used with other drug Main side-effects are dizziness, headaches, depression

Question 35

Preferred treatment of non-cognitive symptoms of AD are

Answer 35

non-pharmacologic approaches

Question 36

Treatment options for Psychosis/agitated behavior in AD

Answer 36

Atypical antipsychotics

Question 37

Treatment options for depression & anxiety in AD

Answer 37

SSRI - safe for elderly, better side effects (sertraline & citalopram) Avoid tricyclics = confusion & falls

Question 38

Treatment options for sleep disturbances

Answer 38

``` Antidepressants, atypical neuroleptics Avoid benzodiazepines (long acting) & antihistamines (anti-cholinergic) ```