Alzheimer's Disease

Question 1

What is mild cognitive impairment (MCI)?

Answer 1

A condition of measurable decreases in memory and mental function, but it is not severe enough to significantly interfere with daily functioning

Question 2

What is the most noticeable symptom of dementia initially?

Answer 2

Memory loss

Question 3

What are the complications associated with dementia?

Answer 3

As dementia worsens, problems develop with judgment, attention, planning and personal grooming

*Agitation, aggression and depression can be present and are difficult challenges for patients and caregivers

Question 4

What are different symptoms of Alzheimer’s disease?

Answer 4

Memory loss, getting lost, difficulty communicating, repeating words and information, inability to learn or remember new information, difficulty with planning and organizing, poor coordination and motor function, personality changes, inappropriate behavior, paranoia, agitation, hallucinations

Question 5

What are the different types of dementia?

Answer 5

Alzheimer’s disease, vascular dementia and Lewy body dementia

Question 6

What is the pathophysiology of Alzheimer’s disease?

Answer 6

The pathophysiology of Alzheimer’s dementia involves neuritic plaques (clusters of beta-amyloid protein) and tangles (accumulation of tau protein) in brain tissue, which interrupt neuron signaling and/or alteration of neurotransmitters (e.g. decreased acetylcholine)

Question 7

How do you make a definitive diagnosis of the cause and type of dementia?

Answer 7

A definitive diagnosis of the cause and type of dementia cannot be made unless an autopsy is conducted post-mortem (after-death)

Question 8

What is flortaucipir F18 (Tauvid) used for?

Answer 8

The FDA approved flortaucipir F18 (Tauvid) as a radioactive imaging drug to estimate the tau protein tangles in adult patients being evaluated for Alzheimer’s disease

Question 9

What is the importance of an early diagnosis with dementia that worsens over time?

Answer 9

With dementia that worsens over time, such as Alzheimer’s disease, an early diagnosis provides a person time to plan for the future while he or she can still participate in decision making

Question 10

What are some reversible causes of memory impairment?

Answer 10

Vitamin B12 deficiency, depression and infection

Question 11

What are some key drugs that can worsen dementia?

Answer 11

Antiemetics, antihistamines, antipsychotics, barbiturates, benzodiazepines, central anticholinergics, peripheral anticholinergics, skeletal muscle relaxants, other CNS depressants

Question 12

What are some screening tools to identify or screen for dementia?

Answer 12

Folstein Mini-Mental State Exam (MMSE, max score is 30, score < 24 indicates a memory disorder), the Montreal Cognitive Assessment (MoCA) and DSM-5 criteria

Question 13

What screening tool can assess functional ability?

Answer 13

Functional abilities can be assessed using the Alzheimer’s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) tool

Question 14

What do these screening tools do?

Answer 14

These screening tools ask the patient a series of questions to evaluate cognitive impairment and/or assess functional abilities with activities of daily living

Question 15

What are anticholinergics used for?

Answer 15

Anticholinergics are used to treat incontinence, allergies or insomnia, dystonic reactions and other conditions

Question 16

What can occur with a drug with a strong centrally-acting anticholinergic effect?

Answer 16

Acute cognitive impairment and sometimes psychosis and hallucinations

Question 17

The effect of strong centrally-acting anticholinergic effects is affected by what?

Answer 17

The effect depends on the patient’s baseline cognitive function, sensitivity to the drug, drug clearance, the number of drugs with additive effects and the dosing schedule

Question 18

Who should avoid centrally acting anticholinergics?

Answer 18

Centrally-acting anticholinergics should be avoided in the elderly due to these risks

*This is a key point of the Beers Criteria

Question 19

What should be done if anticholinergics need to be used to treat incontinence?

Answer 19

If a drug is used to treat incontinence, the reduction in symptoms should be evaluated at six weeks. If there is a lack of improvement, the drug should be discontinued

Question 20

What are some supplements with possible benefit for Alzheimer’s disease?

Answer 20

Vitamin E, gingko, acetyl-L-carnitine, vitamin D

Question 21

What is an adverse effect of Vitamin E and gingko?

Answer 21

Both of these can increase bleeding risk

Question 22

What are some non-pharmacological treatments of Alzheimer’s disease and dementia?

Answer 22

The vascular health of the blood vessels in the brain is vital for cognitive function and to promote vascular health:

• Keep blood glucose, blood pressure and cholesterol well-controlled
• Engage in “thinking” activities and regular physical activity
• Eat a healthy diet, with fruits, vegetables, nuts, fish and with a low intake of red meat and alcohol

Question 23

What is the mainstay treatment of Alzheimer’s disease?

Answer 23

Acetylcholinesterase inhibitors are the mainstay of treatment. They are used alone or with memantine in more advanced stages of the disease

Question 24

What are monitoring parameters for acetylcholinesterase inhibitors?

Answer 24

Patients receiving acetylcholinesterase inhibitors should be monitored for both improvement and side effects

Question 25

When should discontinuation of acetylcholinesterase inhibitors be considered?

Answer 25

Discontinuation is advisable if the dementia has advanced to the point where the drug lacks clinical benefit, though this may not be acceptable to the family and in some patients, there will be a noticeable deterioration when the medication is stopped

Question 26

How can timing of medication administration of acetylcholinesterase inhibitors help reduce adverse effects?

Answer 26

If nausea is present, administration in the evening can help. Donepezil is taken at bedtime for this reason. If insomnia is a concern, the patient can take the dose in the morning

Question 27

What is Memantine approved for and how can it be useful in Alzheimer's disease?

Answer 27

Memantine is approved for use alone or with donepezil for moderate-to-severe disease

Question 28

What is Namzaric?

Answer 28

Namazaric is a combination of donepezil and memantine *Patients stabilized on donepezil 10 mg can be switched to Namzaric

Question 29

What are some examples of acetylcholinesterase inhibitors?

Answer 29

Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne)

Question 30

What are some warnings associated with acetylcholinesterase inhibitors?

Answer 30

- Cardiac effects, including bradycardia, snycope, QT prolongation - Anorexia/weight loss - Patients < 55 kg can have more nausea and weight loss - Neuroleptic malignancy syndrome and rhabdomyolysis (both rare)

Question 31

What are some side effects associated with acetylcholinesterase inhibitors?

Answer 31

Nausea, diarrhea (both dose-related, transient), insomnia, decreased appetite/weight loss

Question 32

What are some counseling points of acetylcholinesterase inhibitors?

Answer 32

- Donepezil is dosed QHS to help decrease nausea - Exelon patch and donepezil ODT have less GI side effects - Exelon patch: apply first patch the day after last oral dose; rotate sites (do not use same site for 14 days) - Exelon capsules and galantamine IR should be taken with breakfast and dinner; galantamine ER should be taken with breakfast - Galantamine solution can be mixed with liquid; drink immediately - If stable on donepezil 10 mg, can switch to Namzaric (memantine 7 mg/donepezil 10 mg QHS) and titrate weekly (minimally)

Question 33

What is the MOA of acetylcholinesterase inhibitors?

Answer 33

Inhibit centrally-active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine which causes an increase in acetylcholine

Question 34

What is the MOA of Memantine?

Answer 34

Blocks NMDA receptors, which inhibits glutamate (an excitatory neurotransmitter) from binding and decrease abnormal neuron activation

Question 35

What are some warnings associated with Memantine?

Answer 35

Caution with drugs/conditions that increase urine pH, which decrease clearance of memantine

Question 36

What are some side effects associated with Memantine?

Answer 36

Generally well-tolerated, can cause dizziness, confusion, headache, constipation, syncope

Question 37

What are some counseling points of Memantine?

Answer 37

- ER capsule and Namzaric: do not crush or chew; capsules can be opened and sprinkled on applesauce (swallow immediately) - Oral solution: use provided dosing device and squirt into mouth

Question 38

What are some acetylcholinesterase inhibitor drug interactions?

Answer 38

- Use caution with other drugs that can lower heart rate and with drugs that cause dizziness - Drugs that have anticholinergic effects can reduce the efficacy of acetylcholinesterase inhibitors - These drugs can increase gastric acid secretion; use cautiously with NSAIDs due to the risk of GI bleeding

Question 39

What are key counseling points for all Alzheimer's disease medications?

Answer 39

Tell your healthcare provider which prescription and over-the-counter medications you are taking; other drugs can worsen memory problems

Question 40

What are some key counseling points for all acetylcholinesterase inhibitors?

Answer 40

Can cause nausea, diarrhea, decreased heart rate

Question 41

What are some key counseling points with the Exelon Patch?

Answer 41

- Apply a new patch at the same time each day to the upper or lower back (preferred sites if patient might remove patch) or on the upper arm or chest - Rotate application sites. Do not use the same site within 14 days - After 24 hours, remove the used patch. Do not touch the sticky side. Fold the patch in half with the sticky sides together and dispose of it safely