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Neurology > Alzheimer's Disease > Flashcards

Alzheimer's Disease Flashcards

1
Q

What is the DSM-IV-TR Criteria for Dementia?

A
  • Memory Impairment (learning new info and recalling old)
    AND
  • One of the following:
    • Aphasia (language disturbance)
    • Apraxia (impaired motor activity ability)
    • Agnosia (failure to recognize objects)
    • Disturbance in executive functioning (planning, organizing, sequencing, abstracting)
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2
Q

What is the DSM-V Criteria for Major Neurocognitive Disorder?

A

Evidence of significant cognitive decline from a previous level of performance in one or more area of cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor or social cognition) based on:
* Concern of the individual, a knowledgeable informant or the clinician that there has been a significant decline in cognitive function
AND
* Substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing, or in its absence, another quantified clinical assessment

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3
Q

What are some symptoms and behaviors in dementia?

A
  • Memory loss
  • Poor judgement
  • Diminished driving skills
  • Disorientation and unadaptability
  • Personality change and disinhibition
  • Communication disorders
  • Demanding and repetitive behaviors
  • Emotional lability and depression
  • Diminished self care skills
  • Insomnia and sundowning
  • Wandering and falling
  • Aggressiveness and catastrophic reactions
  • Delusions and hallucinations
  • Incontinence
  • Late gait disturbances and immobility
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4
Q

Multi-Infarct Dementia

A
  • Abrupt
  • Deterioration: Step-wise
  • PMHx: HBP/ASCVD/CVD
  • ROS/PE: Focal Neuro exam
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5
Q

Alzheimer’s Type

A
  • Insidious
  • Deterioration: Slow, progressive
  • PMHx: Non-cardiac dz
  • ROS/PE: Non-focal neuro exam
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6
Q

What are the most common reversible causes of dementia?

A
  • Drugs
  • Depression
  • Metabolic
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7
Q

What are the drug classes associated with cognitive impairment in the elderly?

A
  • Anticholinergics
  • Anticonvulsants
  • Antihistamines
  • Antiparkinson
  • Analgesic
  • Cardiovascular
  • Gastrointestinal
  • Psychotropics
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8
Q

What are the highest risk anticholinergic drugs?

A
  • Amitriptyline
  • Atropine
  • Benztropine
  • Carisoprodol
  • Dicyclomine
  • Diphenhydramine
  • Hydroxyzine
  • Meclizine
  • Oxybutynin
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9
Q

What are the high risk anticholinergics?

A
  • Amantadine
  • Baclofen
  • Cimetidine
  • Cyclobenzaprine
  • Loperamide
  • Nortriptyline
  • Tolterodine
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10
Q

Dementia vs Delirium

A
  • Decline in cognitive function over time
  • Memory loss
  • Short period of time (hours to days)
  • Acute change in level of consciousness
  • Decline in cognition
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11
Q

What are the risk factors of AD?

A
  • Old age ( > 65 years)
  • Female (2x W>M)
  • Positive family history (Apolipoprotein E4 allele)
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12
Q

What are the early-mid cognitive symptoms of AD?

A
  • Memory deficits
  • loss of inhibitors
  • naming difficulties
  • problems with IADLs
  • social withdrawal
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13
Q

What are the later-moderate cognitive symptoms of AD?

A
  • Comprehension difficulties
  • problems dressing
  • grooming
  • feeding
  • delusions
  • agitation
  • aggression
  • disorientation
  • wandering
  • sleep abnormalities
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14
Q

What are the end-severe cognitive symptoms of AD?

A
  • Rigidity
  • bedridden
  • myoclonic jerks
  • hyperactive reflexes
  • mute
  • incontinent
  • death
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15
Q

What is the pathophysiology of AD?

A
  • Destroys acetylcholine synthesizing neurons (hippocampus & cortex)
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16
Q

What are the four alterations of AD?

A
  • Extracellular B-amyloid plaques
  • Intracellular neurofibrillary tangles
  • Degeneration B-amyloid plaques
  • Cortical atrophy
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17
Q

What are the assessments for AD?

A
  • Diagnosis of exclusion-confirmed on autopsy
  • Folstein Mini-Mental Status Exam (MMSE) or Montreal Cognitive Assessment
  • Alzheimer’s Disease Assessment Scale (ADAS-Cog)
  • Clinician’s Interview Based Impression of Change (CBIC-Plus)
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18
Q

Which drugs are cholinesterase inhibitors?

A
  • Tacrine
  • Donepezil
  • Rivastigmine
  • Galantamine
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19
Q

What is the MOA of cholinesterase inhibitors:

A

Inhibits acetylcholinesterase preventing hydrolysis of acetylcholine, thus increasing acetylcholine in the synaptic cleft

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20
Q

What is the MOA of Tacrine (Cognex)?

A

Centrally acting, competitive, reversible BChE > AChE

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21
Q

What is the place of therapy of Tacrine (Cognex)?

A
  • First cholinesterase inhibitor
  • FDA approved in 1993
  • FDA approved – mild to moderate AD
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22
Q

What are the adverse effects of Tacrine (Cognex)?

A
  • Cholinergic SE
  • Hepatotoxicity – no longer marketed
    • LFT monitoring (50% elevated LFTs)
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23
Q

What are some drug interactions of Tacrine (Cognex)?

A
  • Decreases theophylline metabolism
  • Cimetidine decreases tacrine metabolism
24
Q

What is the MOA of Donepezil?

A

Competitively binds AChE

25
Q

What is the place of therapy of Donepezil?

A
  • Second generation Cholinesterase inhibitor
  • FDA approved in 1996
  • FDA approved indications: mild, moderate, and severe AD
26
Q

What is the dosing of Donepezil?

A
  • Mild to moderate AD dosing: 5 mg once daily; may increase to 10 mg daily after 4-6 weeks; range 5-10 mg/day
  • Moderate to severe AD dosing: 5 mg once daily; may increase to 10 mg daily after 4-6 weeks; may increase further to 23 mg once daily after ≥ 3 months; range 10-23 mg/day
27
Q

What is the adverse effects of Donepezil?

A

(>10%)
* CNS: Insomnia (may need to switch dosing time)
* GI: Nausea, diarrhea (dose-related)

May diminish over time

28
Q

What are some drug interactions of Donepezil?

A
  • Anticholinergics
  • Beta-blockers
  • St. John’s Wort (decreased donepezil levels)

Monitor for HR (may cause bradycardia)

29
Q

What is the place of therapy of Rivastigmine?

A
  • FDA approved indications: mild to moderate AD
  • Mild-moderate dementia associated with Parkinson’s dz
29
Q

What is the MOA of Rivastigmine?

A
  • Pseudoirreversible agent that inhibits centrally acting AChE > peripheral AChE
  • Inhibits BChE
30
Q

What is the dosage of the transdermal patch of Rivastigmine?

A

4.6 mg/24 hours, if well tolerated, may be increased after 4 weeks to 9.5 mg/24 hours

31
Q

What is the conversion from oral Rivastigmine to the patch?

A
  • If daily dose < 6 mg, switch to 4.6 mg/24 hour patch
  • if dose 6-12 mg, switch to 9.5 mg/24 hour patch
32
Q

What are the adverse effects of oral Rivastigmine?

A

(>10%)
* CNS: Dizziness and headache
* GI: Nausea, vomiting, diarrhea, anorexia, abdominal pain

33
Q

What are the adverse effects of transdermal Rivastigmine?

A
  • N/V/D (may be less)
  • Extrapyramidal sx (particularly tremor)
34
Q

What are some clinical pearls of oral Rivastigmine?

A

Should be administered with meals (breakfast or dinner)

35
Q

What are some drug interactions of Rivastigmine?

A

Anticholinergics and beta blockers

36
Q

What is the disadvantage of Rivastigmine?

A
  • BID dosing
  • Longer titration period
37
Q

What is the proper patch use of Rivastigmine?

A
  • Apply 1 patch each day to intact, healthy skin on the upper arm chest, or upper or lower back
  • After 24 hours, remove existing patch and apply new patch to a different skin location (avoid reapplication to the same spot for 14 days)
  • Patches should NOT be cut into pieces
  • After removal, fold patch to press adhesive surfaces together, and discard
38
Q

What is the MOA of Galantamine (Razadyne)?

A

Reversible inhibition of acetylcholinesterase

39
Q

What is the place of therapy of Galantamine (Razadyne)?

A
  • FDA approved February 2001
  • New trade name Razadyne® July 2005 – to avoid confusion with Amaryl®
  • FDA approved indications: mild to moderate AD
40
Q

What are the adverse effects of Galantamine (Razadyne)?

A

N/V/D

41
Q

What are the counseling points of Galantamine (Razadyne)?

A
  • Oral soln or tablet with breakfast and dinner
  • ER cap with breakfast
  • Mix oral soln with 3-4 oz. of any nonalcoholic bev, mix well and drink immediately
42
Q

What is the MOA of Memantine?

A
  • NMDA receptor antagonist
  • Glutamate activates NMDA receptor which is involved in learning and memory. Blocking NMDA may prevent further damage
  • Abnormal glutamatergic activity leads to sustained low level activation of NMDA receptors
  • Leading to neuronal damage/loss and cognitive deficits
43
Q

What is the place of therapy of Memantine?

A

Moderate to severe AD (literature also supports add-on therapy with donepezil)

44
Q

What are the adverse effects of Memantine (Namenda)

A

(1-10%; rated as mild or moderate)
* CNS: Dizziness, headache, somnolence
* GI: Constipation, diarrhea, vomiting

45
Q

What are the drug interactions of Memantine (Namenda)?

A
  • Elimination: Primarily unchanged in urine
  • Trimethoprim – may INCREASE serum conc of memantine, INCREASE risk of myoclonus and delirium
46
Q

Memantine + Donepezil (Namzaric)

A
  • Moderate to severe AD
  • Should be stabilized on donepezil 10 mg/day before starting
47
Q

What are the drug interactions of Memantine + Donepezil (Namzaric)?

A
  • Anticholinergics
  • Beta blockers
  • Trimethoprim
48
Q

Aducanumab (Aduhelm)

A
  • Removed from the market February 2024
  • Patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease
  • Mechanism – anti-amyloid antibody
  • ADE: “ARIA”
49
Q

Lecanemab (Leqembi)

A
  • Indicated for patients with mild cognitive impairment or mild dementia due to Alz dz (early stage)
  • Adverse effects: ARIA-E (10%), ARIA-H (6%), and infusion reactions (20%)
50
Q

What are some behavioral and psychological symptoms of dementia (BPSD)?

A
  • Sundowning
  • Psychosis (7-33%), delusions (30-70%)
  • Sleep disturbances (25-35%)
  • Restlessness, combativeness
  • Wandering, hoarding
  • Hypervocalization
  • Aggression, agitation
  • Hypersexuality
51
Q

What are some BPSD Pharmacological Options?

A
  • Antipsychotics
  • Antidepressants (SSRIs)
  • Antiepileptics (Carbamazepine, Valproate)
  • Benzodiazepines
52
Q

What are some atypical antipsychotics?

A
  • Risperidone
  • Quetiapine
  • Olanzapine
  • Ziprasidone
  • Aripiprazole
53
Q

What are some FDA warnings/issues of atypical antipsychotics?

A
  • Metabolic
  • Cardiac conduction - Prolonged QT interval (Ziprasidone is the worst)
  • Mortality and stroke risk
54
Q

Which atypical antipsychotics are preferred?

A
  • Quetiapine and Olanzapine (low dose)

Neurology (21 decks)

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