Cognitive Enhancing Agents Flashcards

1
Q

According to the 2011 AD criteria-phases, when does MCI and Dementia begin?

A

MCI

  • Cognitive impairment presents on neuropsychological testing
  • ~1/3 decline from baseline

Dementia

  • Evidence of clinically significant impairment
  • ~2/3 decline from baseline
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2
Q

What are the biomarkers of Aß accumulation?

A

Abnormal tracer retention on amyloid PET

Low CSF Aß42

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3
Q

What are the biomarkers of neuronal degeneration or injury?

A

Elevated CSF tau
Decreased fluorodeoxyglucose uptake on PET
Atrophy on structural MRI

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4
Q

What chromosome increases the risk of AD by 10 to 30 times?

A

Chromosome 19

- APOE e4

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5
Q

What is the primary effect of pharmacotherapy in treating dementia?

A

Slowing the rate of decline

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6
Q

What drugs are included in acetylcholinesterase inhibitors?

A

Tacrine- DC in US because of liver failure
Donepezil
Rivastigmine
Galantamine

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7
Q

What is the dominant drug used for dementia?

A

Donepezil

- Only FDA approval for AD

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8
Q

Why is Donepezil given in the AM?

A

To avoid nightmares

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9
Q

What other adverse effects are associated with Donepezil?

A

Nausea/Diarrhea/Lacrimation/Salvation- Cholinergic effects

Syncope

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10
Q

What are contraindications to Donepezil use?

A
Severe heart disease
Severe cardiac conduction disturbances
Bradycardia
Pacemaker placement
Hip fracature
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11
Q

What common symptom associated with dementai does Donepezil help reduce?

A

Agitation

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12
Q

What type of cholinesterase inhibitor is Rivastigmine?

Central vs Peripheral

A

Central

- AChE and BuChE inhibitor

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13
Q

What can patients do to help reduce side effects of Rivastigmine?

A

Take it with a large meal
Titrate slowly
*Side effect profile similar to Donepezil

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14
Q

What is a benefit of Rivastigmine?

A

No significant DDI or hepatic metabolism

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15
Q

What kind of cholinesterase inhibitor is Galantamine?

What other receptors does it act on?

A

Central

Nicotinergic receptors

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16
Q

Why might you not want to Galantamine to treat MCI?

A

Increases death rate

17
Q

Why are cholinesterase inhibitors not recommended for MCI in general?

A

No improvement

No affect on progression

18
Q

What are the NMDA antagonists used to help with dementia?

A

Memantine- Only approved drug of the class

19
Q

How does memantine work to treat dementia?

A

Glutamate activity is decreased
There is less Ca influx into cells
There is less abnormal neural cell fixation and death

20
Q

How can memantine be used with AChE inhibitors?

A

They can be used together

21
Q

Why do you want to avoid giving memantine along with sodium bicarb or carbonic anhydrase inhibitors?

A

These drugs alkalize the urine, which decreases clearance of memantine by 80% (toxicity).

22
Q

Why is not advised to coadminster memantine with amantadine, ketamine, or dextromethorphan?

A

These drugs are also NMDA antagonists

May cause toxicity

23
Q

Why is it not advised to coaminister memantine with hydrochlorothiazide, triaterene, cimetidine, ranitidine, quinidine, or nicotine?

A

These drugs are also secreted by the renal tubules.

May lead to toxicity of any one of the medications.

24
Q

What are the common adverse effects of memantine?

A

Dizziness
Headache
Constipation

25
Q

How effective is ginko biloba in treating dementia?

A

It improves general cognitive function, but findings were mixed on how much it improves global assessments

26
Q

What are the adverse effects of Ginko Bilboa?

A

GI upset
Headaches
Dizziness

27
Q

What disorder or medications, if present, would you not want administer Ginko Biloba?

A

Bleeding disorders

Anticoagulants

28
Q

What role do NSAIDs play in the treatment of dementia?

A

They help reduce the risk of onset and rate of progression

- However, they did not show benefit in preventing or altering the course of AD

29
Q

What is the MOA of Bapineuzumab?

A

Humanized monoclonal antibody
Targets ß-amyloid
Promote immune clearance of amyloid

30
Q

How effective is Bapineuzumab?

A

Some clinical benefit was seen in phase II FDA study

31
Q

What is the MOA of Solamezumab?

What region of amyloid does it bind to?

A

Humanized monoclonal AB
Central hydrophobic region
- higher affinity for soluble form of amyloid

32
Q

How effective was Solamezumab?

A

Decreased CSF amyloid

No change in ADAS scores

33
Q

How effective has IVIG been at treating dementia?

A

No change ins ADAS

Neuropsychiatric inventory has shown improvement

34
Q

What immunizations may become availabe in the future?

A
Phospho-tau vaccine
- Reduced CSF tau protein (rats only)
PHF-1
- AB against tau protein
- Reduced tau in rats
- Early human trials
35
Q

What are the recommended drugs to be used to treat agitation associated with dementia?

A

Antipsychotics

- Riperidone and Olanzapine

36
Q

What patients have the best response to antipsychotics?

A

Patient without psychosis
Nursing home patients
Patients with more severe cognitive impairment

37
Q

What adverse effect does adding an antipsycotic have on patients with dementia?

A

Increase mortality

  • Typical > Atypical
  • Cerebrovascular, cardiovascular, and infections
38
Q

What is the neurotransmitter of cognition?

A

Acetylcholine