Alzheimer's and Dementia

Question 1

What is dementia?

Answer 1

Loss of memory and other intellectual functioning which interferes with daily life?

Question 2

Give three types of dementia other than Alzheimer’s

Answer 2

1. Vascular dementia - post-stroke with rapid course
2. Mixed dementia - vascular + Alzheimer’s
3. Lewy body dementia - Progressive and rapid dementia with fluctuating cognition. Movement disturbances and psychoses with interruption of REM sleep is common. (Robin Williams)

Question 3

What is MCI and how is it relevant to AD?

Answer 3

Mild cognitive impairment - cognitive decline greater than expected for one’s age / education.

May be the pre-dementia / transitional state to AD

Question 4

What are the later cognitive abilities affected by AD and what is this called?

Answer 4

Ability to calculate and use common tools (ideomotor apraxia)

Question 5

What is the most common cause of death due to AD?

Answer 5

Complications of immobility (like PD) -> pneumonia and pulmonary embolism

Question 6

What appears in the brain in Alzheimer’s disease? What are they made of?

Answer 6

Atrophy of cerebral cortex, with beta-amyloid plaques outside the nerves, and neurofibrillary tangles made out of hyperphosphorylated tau protein (stabilizes microtubules normally)

Question 7

Give the three acetylcholinesterase inhibitors used for the treatment of Alzheimer’s dementia. Give whether these drugs are reversible or irreversible.

Answer 7

1. Donepezil
2. Rivastigmine
3. Galantamine

All are reversible, but rivastigmine is noncompetitive

Question 8

What drug is preferable of these three and why specifically?

Answer 8

Rivastigmine - has no drug-drug interactions in metabolism, metabolized by cholinesterase hydrolysis

Donepezil and Galantamine are metabolized by CYP2D6 and CYP3A4

Question 9

What is the first disease-modifying drug of Alzheimer’s and how does it work?

Answer 9

Memantine - uncompetitive NMDA receptor antagonist, stabilizes inactive state of the NMDA channel and prevents calcium passage.

NMDA is thought to cause excitotoxicity

Question 10

What other symptoms of Alzheimer’s does memantine treat and what can it be used with? Why?

Answer 10

Manages aggression / agitation as well

Can be used with cholinesterase inhibitors because memantine is excreted in the urine unchanged -> no drug interactions

Question 11

What are the psychotic symptoms of Alzheimer’s? What drugs can treat these?

Answer 11

Outbursts, restlessness, hallucinations

Treat irritability with antidepressants, and restlessness with anxiolytics

Question 12

Why should antipsychotic drugs not be used in the treatment of Alzheimer’s disease?

Answer 12

Black box warning of 2x increased risk of death due to heart attack and infections

Question 13

How is psychosis in Lewy body dementia treated? Why?

Answer 13

Clozapine or pimavanserin,

APDs have a very high risk as well -> sedation, parkinsonism, neuroleptic malignant syndrome

Question 14

Give three drug targets of new anti-Alzheimer’s therapies.

Answer 14

1. Anti-amyloid therapies - active or passive immunization
2. Gamma-secretase inhibitors -> inhibit the enzyme which cleaves amyloid precursor proteins to alpha-beta.
3. Amyloid aggregation inhibitors

Question 15

What is the problem with gamma-secretase inhibitors?

Answer 15

The gamma-secretase enzyme has many other functions in the brain than just cleavage of amyloid precursor protein.

Question 16

What is the new frontier for how big pharma wants to treat Alzheimer’s patients and how do they do this?

Answer 16

Early treatment of patients, see if drug reduces amyloid plaques in PET scans years ahead of time, and see whether this reduces disease course

-> detected by radiologist in PET scan, basically only applicable if you have autosomal dominant AD

Question 17

What was found in the brains of all people who were NFL players and had CTE?

Answer 17

phosphorylated tau protein

Progressive cognitive impairment

Question 18

What is anticholinergic burden associated with in the elderly?

Answer 18

Lower cognitive function and higher diagnose of MCI if they are taking these drugs (antihistamines, antidepressants, and painkillers with anticholinergic / sedative activity)

Question 19

What is hospital delirium? What causes it?

Answer 19

Sudden state of confusion accompanied by hallucinations and agitation, probably due to the medication burden, infections, electrolyte imbalances, lack of normal home amenities, and surgery / procedures

Question 20

Do only demented patients get hospital delirium? How can this be prevented?

Answer 20

No - just affects elderly people over 70 who were not previously demented

Can be prevented by avoiding sedation, orienting the patient, and not keeping them up at night. Just be more empathetic and try to make them feel at home

Question 21

Why is hospital delirium bad for outcomes?

Answer 21

Extends hospitalization, makes them more likely to be placed in nursing home / rehab, and increases likelihood of death or dementia

Question 22

What is one interesting risk factor for dementia?

Answer 22

Hearing loss - highly correlated, could be due to social isolation or increased cognitive load to hear

Question 23

What are the modifiable risk factors for dementia?

Answer 23

Everything related to CVD health (i.e. smoking and dyslipidemia), and anticholinergic burden

Question 24

What are the protective factors against dementia?

Answer 24

Cognitive reserve (i.e. education, mental stimulation)
Physical activity

Question 25

What should be the first treatment for Alzheimer’s disease?

Answer 25

Lifestyle intervention - brighter lights, easier layout of home, use of activities and food for positive emotional context

Make sure to reduce the stress of caregiver

Question 26

What is the first line pharmacologic treatment for AD and what should be done if one is not well tolerated?

Answer 26

Slowly titrated cholinesterase inhibitors (to reduce side effects)

If not well titrated, give 1 week washout and switch to another.

After that, try memantine / AChEI combination

Question 27

What stage of disease should memantine be used in?

Answer 27

Moderate to severe AD or dementia