dementia & alzheimer disease - dr miller

she said 1 exam question from each learning objective *wink wink*

what are the most substantial heritable contributors to genetic risk of AD? (SATA)

a. APOE

b. ABCA7

c. TREM2

d. PICALM

a. b.

alterations on chromosomes 1, 14, or 21 impact the processing of the _______

amyloid precursor protein (APP)

list environmental risk factors for alzheimer’s

age

decr. brain reserve capacity

head injury

down syndrome

depression

MCI

risk factors for vascular disease

KNOW THIS

genetic susceptibility to late-onset AD is primarily linked to which of the following?

a. apolipoprotein E4 genotype

b. presenlin gene mutations

c. amyloid precursor protein mutations

d. apolipoprotein E2 genotype

a.

what is the main proposed pathophysiologic mechanism for AD?

signature lesions

higher burden of plaques and NFTs

______ protein provides structural support

Tau

______ of cholinergic activity correlates with AD severity

loss

_______ therapies minimize or improve symptoms by augmentation of cholinergic neurotransmission at remaining synapses

cholinergic

what is the inflammatory mediator hypothesis?

some of beta-amyloid toxicity may be an indirect consequence of an immune response

attempt to clear amyloid

release of cytokines, NO, other radical species, and complement factors can injure neurons and promote inflammation

is there more or less serotonin in brains of pts with AD?

less

_____ is responsible for transporting cholesterol in the blood and through the brain and interacts with beta-amyloid in almost all pathways

apolipoprotein E (APOE)

the APOE*4 allele is associated with __________ in AD

modified clearance and increased deposition of beta-amyloid

how can high cholesterol lead to AD?

alter membrane functioning

leads to plaque formation

which of the following is TRUE regarding the pathophysiology of AD?

a. caused by amyloid plaques

b. caused by neurofibrillary tangles

c. caused by inflammatory brain processes

d. cause is NOT completely understood

d.

what stage of AD is an MMSE Score of 26-21?

a. mild

b. moderate

c. severe

a.

what stage of AD is an MMSE Score of 20-10?

a. mild

b. moderate

c. severe

b.

what stage of AD is an MMSE Score of 9-0?

a. mild

b. moderate

c. severe

c.

in what AD stage does functioning fluctuate from day to day?

moderate

what AD stage requires 24/7 care?

severe: 9-0

list cognitive symptoms of AD

memory loss

aphasia

apraxia

agnosia

disorientation

impaired executive function

list functional symptoms of AD

inability to care:

eating

toileting

bathing

dressing

list neuropsychiatric symptoms

depression

hallucinations

delusions

physical and verbal aggression

motor hyperactivity

uncooperativeness

wandering

repetitive mannerisms and activities

combativeness

what labs/imaging is SUPPORTIVE of clinical diagnosis?

brain imaging

CSF testing

plasma AD biomarkers

how do you confirm clinical diagnosis of AD?

direct examination of brain tissue

-autopsy

-biopsy

T/F the definitive diagnosis of AD is done through brain MRI

FALSE — it’s a clinical diagnosis

only way to confirm is to examine brain tissue (autopsy, biopsy)

list nonpharm tx options for AD

AVOID:

confrontation

list nonpharm tx options for AD

MAINTAIN:

consistent, structured environment

appropriate stimulation level

SCHEDULE

list nonpharm tx options for AD

PROVIDE:

frequent reminders, explanations, and orientation cues

list nonpharm tx options for AD:

REDUCE:

choices, keep requests and demands simple

list nonpharm tx options for AD:

how can you manage brain vascular disease?

monitor blood pressure, glucose, and cholesterol

what is the primary goal of treatment in AD?

treat cognitive difficulties symptomatically and preserve patient function for as long as possible

what are the secondary goals of AD treatment?

managing psychiatric and behavioral sequelae

list the cholinesterase inhibitors

donepezil (Aricept, Adlarity)

rivastigmine (Exelon)

galantamine (Razadyne)

list the NMDA receptor antagonists

memantine (Namenda)

list the cholinesterase inhibitor + NMDA receptor antagonist

donepezil + memantine (Namzaric)

list the anti-amyloid monoclonal antibodies

donanemab (Kisunla)

lecanemab (Leqembi)

if someone has mild cognitive impairment, what pharm treatment should they be given?

anti-amyloid mAb

if someone has mild-moderate AD, what pharm treatment should they be given?

cholinesterase inhibitors

if someone has moderate-severe AD, what pharm treatment should they be given?

NMDA receptor antagonist ± cholinesterase inhibitor

list ADRs of cholinesterase inhibitors (donepezil, rivastigmine, galantamine)

dizziness

syncope

bradycardia

atrial arrhythmias

MI

n/v/d

anorexia

weight loss

what do you need to monitor for with cholinesterase inhibitors (donepezil, rivastigmine, galantamine)?

dizziness/falls

pulse

BP

postural BP change

list ADRs of donepezil (aricept)

PUD

GI bleeding

insomnia

vivid/abnormal dreams

nightmare

list ADRs of rivastigmine (exelon)

allergic dermatitis

what AD med can lead to serious skin reactions (SJS)?

galantamine (razadyne)

what AD agent is an uncompetitive antagonist of the NMDA type of glutamate receptors?

memantine (namenda)

list ADRs of memantine (namenda)

headache

confusion

dizziness

hallucinations

constipation

when do we use combination therapy for AD?

why?

moderate-severe

slows cognitive and functional decline more

memantine may mitigate GI side effects of cholinesterase inhibitors

what are the ADRs associated with anti-amyloid monoclonal antibodies (mAb)?

ARIA — amyloid-related imaging abnormalities

infusion-related reactions

what drug class is contraindicated with homozygous APOE*4 allele?

anti-amyloid mAbs (donanemab, lecanemab)

when do we use pharmacotherapy for neuropsychiatric symptoms?

when NONPHARM therapies FAILED

what class of antidepressants should be avoided due to anticholinergic activity?

a. SSRIs

b. SNRIs

c. MAOIs

d. tricyclic antidepressants

d.

what is the BBW for antipsychotics?

increased mortality in elderly pts with dementia related psychosis