Cognitive Enhancing Agents

Question 1

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

Answer 1

MCI

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

Dementia

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

Question 2

What are the biomarkers of Aß accumulation?

Answer 2

Abnormal tracer retention on amyloid PET

Low CSF Aß42

Question 3

What are the biomarkers of neuronal degeneration or injury?

Answer 3

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

Question 4

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

Answer 4

Chromosome 19

- APOE e4

Question 5

What is the primary effect of pharmacotherapy in treating dementia?

Answer 5

Slowing the rate of decline

Question 6

What drugs are included in acetylcholinesterase inhibitors?

Answer 6

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

Question 7

What is the dominant drug used for dementia?

Answer 7

Donepezil

- Only FDA approval for AD

Question 8

Why is Donepezil given in the AM?

Answer 8

To avoid nightmares

Question 9

What other adverse effects are associated with Donepezil?

Answer 9

Nausea/Diarrhea/Lacrimation/Salvation- Cholinergic effects

Syncope

Question 10

What are contraindications to Donepezil use?

Answer 10

Severe heart disease
Severe cardiac conduction disturbances
Bradycardia
Pacemaker placement
Hip fracature

Question 11

What common symptom associated with dementai does Donepezil help reduce?

Answer 11

Agitation

Question 12

What type of cholinesterase inhibitor is Rivastigmine?

Central vs Peripheral

Answer 12

Central

- AChE and BuChE inhibitor

Question 13

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

Answer 13

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

Question 14

What is a benefit of Rivastigmine?

Answer 14

No significant DDI or hepatic metabolism

Question 15

What kind of cholinesterase inhibitor is Galantamine?

What other receptors does it act on?

Answer 15

Central

Nicotinergic receptors

Question 16

Why might you not want to Galantamine to treat MCI?

Answer 16

Increases death rate

Question 17

Why are cholinesterase inhibitors not recommended for MCI in general?

Answer 17

No improvement

No affect on progression

Question 18

What are the NMDA antagonists used to help with dementia?

Answer 18

Memantine- Only approved drug of the class

Question 19

How does memantine work to treat dementia?

Answer 19

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

Question 20

How can memantine be used with AChE inhibitors?

Answer 20

They can be used together

Question 21

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

Answer 21

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

Question 22

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

Answer 22

These drugs are also NMDA antagonists

May cause toxicity

Question 23

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

Answer 23

These drugs are also secreted by the renal tubules.

May lead to toxicity of any one of the medications.

Question 24

What are the common adverse effects of memantine?

Answer 24

Dizziness
Headache
Constipation

Question 25

How effective is ginko biloba in treating dementia?

Answer 25

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

Question 26

What are the adverse effects of Ginko Bilboa?

Answer 26

GI upset
Headaches
Dizziness

Question 27

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

Answer 27

Bleeding disorders

Anticoagulants

Question 28

What role do NSAIDs play in the treatment of dementia?

Answer 28

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

Question 29

What is the MOA of Bapineuzumab?

Answer 29

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

Question 30

How effective is Bapineuzumab?

Answer 30

Some clinical benefit was seen in phase II FDA study

Question 31

What is the MOA of Solamezumab?

What region of amyloid does it bind to?

Answer 31

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

Question 32

How effective was Solamezumab?

Answer 32

Decreased CSF amyloid

No change in ADAS scores

Question 33

How effective has IVIG been at treating dementia?

Answer 33

No change ins ADAS

Neuropsychiatric inventory has shown improvement

Question 34

What immunizations may become availabe in the future?

Answer 34

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

Question 35

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

Answer 35

Antipsychotics

- Riperidone and Olanzapine

Question 36

What patients have the best response to antipsychotics?

Answer 36

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

Question 37

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

Answer 37

Increase mortality

• Typical > Atypical
• Cerebrovascular, cardiovascular, and infections

Question 38

What is the neurotransmitter of cognition?

Answer 38

Acetylcholine