Geriatrics Part 2 HL Exam 4

Can AD or PD be cured?

No

What is early onset AD?

Age < 60 and accounts for 1% of cases which are usually genetic

What may cause early onset AD?

mutations in APP, PSEN1, or PSEN2

follows an autosomal dominant pattern in 50% of cases

What is late onset AD?

Age 80+ and is more environmental rather than genetic

What may cause late onset AD?

ApoE gene is a strong RF (especially E4 variant)

What is the primary NT shortage seen in AD?

Acetylcholine (ACh)

Why is there a ACh shortage in AD?

pathways are damaged by plaques and tangles which leads to learning and memory impairment

What role does cholesterol play in AD?

increased concentrations are associated with AD due to increased beta-amyloid protein synthesis which can lead to plaque formation + the ApoE4 allele is thought to be involved with cholesterol metabolism (higher risk)

What are the components of the DSM-5 diagnostic criteria for major neurocognitive disorders?

1. evidence of significant cognitive decline from baseline (complex attention, executive fxn, learning/memory, language, perceptual motor, social cognition)

2. cognitive deficits interfere with independence in everyday activities

3. cognitive deficits do not occur exclusively with delirium

4. cognitive deficits are not explained by another mental disorder

What are components of the DSM-5 diagnostic criteria for mild neurocognitive disorders?

same as major disorders, but modest cognitive decline is present (not significant)

What are the components of the DSM-5 diagnostic criteria for major/mild neurocognitive disorder due to AD?

1. criteria are met for major or mild neurocognitive disorder

2. insidious onset and gradual progression of impairment in 1+ cognitive domain (for major, 2+ domains must be impaired)

3. criteria are met for probable/possible AD

4. disturbance is NOT explained by cerebrovascular disease, another neurodegenerative disease, substance effects, or another mental/neuro/systematic disorder

What are the criteria for probably AD in major neurocognitive disorders?

3-1. evidence of causative AD genetic mutation from fam hx or testing

3-2. clear decline in memory/learning and 1+ other domain AND steadily progressive gradual decline in cognition without plateaus AND no evidence of mixed etiology

What are the criteria for probably AD in mild neurocognitive disorders?

Probable AD: diagnosed if evidence of causative AD genetic mutation from fam hx or testing

Possible AD: diagnosed if there is no evidence of causative AD mutation, but clear decline in memory/learning AND steadily progressive gradual decline in cognition without plateaus AND no evidence of mixed etiology

An older adult is having difficulty paying bills on time. Is this consistent with dementia? If so, what stage? (mild, moderate, severe)

Mild

A male assisted living facility resident with suspicions that the staff is stealing money from him and that his neighbor is having an affair with his wife. He became angry and hit his roommate today. Is this consistent with dementia? If so, what stage? (mild, moderate, severe)

Mod

A female nursing home resident who no longer remembers the names of or consistently recognizes her adult children or sometimes thinks her son is her deceased husband. Is this consistent with dementia? If so, what stage? (mild, moderate, severe)

Severe (consistent with dementia)

When should therapy for AD be started?

asap after diagnosis

What are the goals of AD treatment?

delaying disease progression

preservation of functioning as long as possible

secondary: treating psych and behavioral symptoms

What class of agents are first-line in treating cognitive symptoms of AD?

AChE inhibitors and/or NMDA antagonists (i.e., memantine)

What is a reasonable trial to determine efficacy?

3-6 months

What would you recommend if a AChE inhibitor is ineffective?

switch to another AChE inhibitor

What is a reasonable trial in terms of tolerability?

4+ weeks

What would you recommend if a patient experienced intolerable ADRs with cholinesterase inhibitors?

D/C and consider other treatment

What does MMSE stand for?

mini mental state exam

What indicates a mild score on a MMSE?

21-24

What indicates a moderate score on a MMSE?

10-20

What indicates a severe score on a MMSE?

< 10

Which class/medication is FDA-approved for moderate to severe AD only (not mild)?

memantine

What are first line options for AD?

donepezil, galantamine, rivastigmine

Which medication is used to treat mild, mod, and severe AD?

donepezil

What are common side effects of donepezil?

Mild - Mod GI symptoms:

N (least likely in class)

Diarrhea

HA

Insomnia

What is the titration schedule of donepezil?

5mg QPM

→ 4-6 weeks

→ 10mg

→ 3 months

→ 23mg

True or False: donepezil does not require renal adjustments

True

What are drug interactions of donepezil?

CYP 2D6 or 3A3/4 inhibitors (concern for peripheral side effects)

CYP 2D6 or 3A3/4 inducers (increase elimination rate of donepezil)

What does galantamine and rivastigmine treat?

mild-mod AD

What are the most common side effects of galantamine?

Cholinergic (common):

N (> Donep but < Rivas)

V

Diarrhea

Dizziness

What is the titration schedule of galantamine?

IR:

4mg BID

→ 4 weeks

→ 8-12mg bid

ER:

8mg QAM

→ 4 weeks

→ 16-24mg qd

When are dose adjustments indicated for galantamine?

Do not exceed 16mg for mod impaired hepatic/renal fxn

C/I in severe dysfxn

True or False: there are no important drug interactions of galantamine

True

What are common side effects of rivastigmine?

N/V >>> (compared to donep, galan)

Dizziness

Anorexia

Diarrhea

HA

What is the titration schedule of rivastigmine?

PO:

1.5mg BID

→ 2 weeks

→ 3-6mg BID

Patch: QD

4.6mg/24hr

→ 4 weeks

→ 9.5mg/24hr

When are dose adjustments indicated for rivastigmine?

Max dose of 4.6mg/24hr if...

- Mod-severe renal impairment

- Mild-mod hepatic impairment

- Low body weight (< 50kg)

When is memantine used for AD?

mod-severe (not mild)

What are common side effects of memantine?

Minimal!

Most common: dizziness, HA

Also:

Constipation

Confusion

Coughing

HTN

What is the dose titration of memantine?

IR:

5mg QD

→ 1 week

→ 10mg BID

ER:

7mg QD

→ 1 week

→ 28mg QD

When are dose adjustments indicated for memantine?

Severe renal impairment: target maintenance dose of 5 mg twice daily or 14 mg daily

When are anti-amyloid therapies used for AD?

mild AD

What are common side effects of anti-amyloid therapies for AD?

Infusion related rxns

Amyloid related imaging abnormalities (ARIA)

ARIA edema or effusions

HA

Falls

What are examples of anti-amyloid therapies?

lecanemab and donanemab

Why was vitamin E recommended for AD?

antioxidant properties, but not recommended much anymore and don't exceed 400IU daily (increases mortality)

Why are NSAIDs not used for AD?

not really any data and ADRs (gastritis, GI bleeds, increased CV events)

When are statins used in AD?

only if there's an indication for it

Would we recommend gingko bioba for AD?

sure, has long-term safety and efficacy, but recommend with caution

What is caprylidene?

medical food that increases ACh in the brain which is potentially useful in AD

How to reduce dementia risks?

Monitoring BP

Monitoring glucose

Monitoring cholesterol

Monitoring homocysteine

Initiating appropriate interventions

What should be considered as first-line treatment for behavioral symptoms associated with AD?

Nonpharm:

- Music

- Videotapes of family members

- Audiotapes of the voices of caregivers

- Walking and light exercise

- Sensory stimulation and relaxation

Pharm: Antipsychotics +/- Antidepressants

List most commonly used agents to treat psychosis associated with AD:

Atypical Antipsychotics:

- Olanzapine

- Aripiprazole

- Quetiapine

- Risperidone

How common is depression in AD patients?

50% of patients

What are S/S of depression in AD?

often similar to dementia

Poor appetite

Insomnia

Hopelessness

Anhedonia

Withdrawal

Suicidal thoughts

Agitation

What class is used for depression in AD?

SSRIs

What other agents are used to treat anxiety or agitation associated with AD?

Benzos (anxiety, agitation, aggression)

Anticonvulsants (alternatives for anxiety, agitation, aggression)

Buspirone (agitation and aggression)

Selegline (anxiety, depression, agitation)

Trazodone (insomnia, agitation, dysphoria, sundowning)

What are risk of benzos?

increased falls

Which anticonvulsants are used for anxiety/agitation in AD?

CBZ, VPA, gabapentin

True or False: buspirone has a ton of ADRs

False (minimal ADRs)

What is the MOA of selegline?

MAO inhibitor (this class is usually not tolerated well, but this particular one is okay for depression in AD)

What are monitoring parameters for AD treatment?

therapy success, develop plan, quality of life, functional performance/mood/behaviors, and evaluate ADRs/allergies/interactions

What part of the brain is affected in PD?

DA neurons in the substantia nigra are primarily affected → disruption in smooth motor control

What is the primary NT target for PD drug therapy?

As dopamine (DA) neurons die, DA relayed messages cannot communicate to other motor centers of the brain, and patients develop motor symptoms

List some common drugs that can cause drug-induced PD

It is essential to rule out drug-induced pseudoparkinsonism due to dopamine antagonists such as antipsychotics, metoclopramide, and antiemetics (prochlorperazine) before diagnosis

What are the four hallmark motor features of PD?

TRAP:

tremor at rest: "pill-rolling"

rigidity: stiff and cogwheel rigidity

akinesia (or bradykinesia)

postural instability (and gait abnormalities)

What are the nonmotor features of PD?

SOAP:

sleep disturbances

other (misc):

NA

Fatigue

Speech

Pain

Dysethesias

Vision problems

Seborrhea

autonomic:

Drooling

Constipation

Sexual dysfxn

Urinary problems

Sweating

Orthostatic hypotension

Dysphagia

psych:

Anxiety

Psychosis

Cognitive impairment

Depression

What are response fluctuations to PD?

MAD:

motor fluctuations (delayed on, wearing off, random off, freezing)

akathisia

dyskinesia (chorea, dystonia, diphasic dyskinesia)

When should medication therapy for PD be initiated?

Pharm therapy depends on age, risk of ADRs, degree of physical impairment, and readiness to initiate therapy

**figure**

What is the role of a dietician in PD?

recommend appropriate caloric intake, meal selection, and protein consumption which may (a) improve constipation (b) decrease weight loss and aspiration (c) minimize erratic drug absorption

What is the role of a speech therapist in PD?

improve swallowing, articulation, and force of speech

What is the role of a physical therapist in PD?

improve strength, activity, sleep quality, and reduce fall risk

What is the role of an occupational therapist in PD?

educate on adaptive environment of home, specialized clothing, and personal training to maximize (a) independence (b) safety (c) ADRs toleration (d) driving ability

What are side effects seen in all PD meds?

N/V

hypotension

hallucinations

What is the MOA of benztropine?

anticholinergic

What are dosing notes of benztropine?

Good for tremor and drooling, but not other symptoms.

Not for elderly patients.

What are side effects of benztropine?

Cognitive impairment

Inhibition of GI motility

Worsen urinary retention and/or constipation

What is the MOA of selegiline and rasagiline?

MAO-B inhibitors that decrease DA metabolism

What are dosing notes of selegiline?

Available as ODT (avoids first-pass metabolism)

Avoid tyramine-containing foods

Has amphetamine like metabolite do not dose in evening

What are side effects of selegiline?

NA

Confusion

Hallucinations

Jitteriness

Insomnia

Orthostatic hypotension

What are dosing notes of rasagiline?

Avoid tyramine-containing foods

What are side effects of rasagiline?

similar to selegiline, but has LESS insomnia

What is the MOA of amantadine?

NMDA receptor antagonist: blocks glutamate transmission, promotes DA release, and blocks ACh

What are dosing notes of amantadine?

ER formulations approved specifically for dyskinesias

Some patients develop tolerance and need to be tapered off for a drug holiday

Niche: when everything else is not working → smoothes peak dose dyskinesias

What are side effects of amantadine?

NA

Dizziness

Livedo reticularis

Peripheral edema

Orthostatic hypotension

Hallucinations

Restlessness

ACh effects

Insomnia (ER limits this)

What is the MOA of ropinirole, pramipexole, and apomorphine?

DA agonists

What are dosing notes of ropinirole?

Delay levodopa therapy and decrease risk of motor fluctuations

CYP1A2 = metabolism induced by smoking

Hepatically metabolized

What are dosing notes of pramipexole?

Delay levodopa therapy and decrease the risk of motor fluctuations

Eliminated unchanged in the urine = no liver

What are dosing notes of apomorphine?

SQ injection for acute off episodes

SQ injection with quick onset (10 minutes)

Delay levodopa therapy and decrease the risk of motor fluctuations

USED PRN up to 5x daily

This drug does not allow us to decrease the dose of carb/levo

What are side effects of ropinirole and pramipexole?

Common:

NA

Sedation

Pedal edema

Orthostatic hypotension

Psychiatric effects (more than levodopa)

Nightmares

Confusion

Hallucinations

Excessive daytime sleepiness

Sleep attacks

Rare:

Painful reddish discoloration of skin (shins, pleuropulmonary)

Retroperitoneal

Cardiac fibrosis

What are side effects of apomorphine?

same as the other DA agonists, but you have to pre-medicate with antiemetic

What is the MOA of carbidopa/levodopa?

Carbidopa: peripheral AADC inhibitor

Levodopa: converted into DA in CNS

What are dosing notes of carbidopa/levodopa?

At least 75 mg carbidopa/day for effectiveness.

Start at a very low dose to minimize adverse effects.

May dose every 2 hrs in advanced PD.

What are side effects of carbidopa/levodopa?

Initial: take with nonprotein food to limit

Orthostatic hypotension

Anorexia

N/V

Urine discoloration

Late:

Dyskinesia

Sleep attacks

Impulse control disorders

Hallucinations

Nightmares

Confusion

Altered behavior

What is the MOA of entacapone and opicapone?

COMT Inhibitor: decreases metabolism of DA

What are dosing notes of entacapone?

ineffective as monotherapy