Dementia

Question 1

Dementia Prevalence

Answer 1

• As the population age increases, the prevalence of dementia increases

Question 2

Define Dementia

Answer 2

clinical syndrome characterized by progressive cognitive decline that interferes with the individual’s ability to function independently

Question 3

Define Cognition

Answer 3

all of the mental processes involved in learning, remembering, and using knowledge

Question 4

Define Mild COgnitive Impairment

Answer 4

Modest decline in cognition from previous. This decline does not interfere with ability to function independently. May or may not progress to dementia.

Question 5

Describe relationship between demntia and delirium

Answer 5

o Individuals with dementia are particularly vulnerable to developing delirium
o Individuals that have experienced delirium are at increased risk of developing dementia

Question 6

What must occur first for dementia management?

Answer 6

• Reversible causes of cognitive impairment (DEMENTIA): need to be ruled out or managed before diagnosis of dementia

Question 7

What are some reversibale causes of demntia

Answer 7

o Drugs (including alcohol)
 Anticholinergics: cumulative anticholinergic exposure increases risk for subsequent dementia!
 Otherwise, pretty much the same as delirium
o Emotional (depression)
o Metabolic, electrolytes, endocrine
o Eyes and Ears declining
o Nutritional (B12 deficiency)
o Tumor or other space-occupying lesion
o Infection (neurosyphilis, HIV)
o Anemia

Question 8

Describe alzheimer DIsease

Answer 8

o Most common
o Usually starts with short-term memory loss and slowly progresses to all areas of functioning
o Associated with characteristic beta-amyloid plaques and neurofibrillary tangles. Can see cerebral atrophy upon head CT.

Question 9

Etyiology, Risk FActors and Prevention of AD

Answer 9

Etiology unclear; likely a mix of genetic, environmental, and social factors
o Risk factors: increased age, family history, genetic mutations, history of severe head trauma, mild cognitive impairment, and lifestyle (lack of exercise, obesity, smoking, etc.)
o Education, social engagement, and lifelong learning is protective

Question 10

Describe VAcular Dementia

Answer 10

o Results from interrupted blood flow in parts of the brain. Damage is usually visible on MRI and CT and there are usually CV risk factors
o Onset may be abrupt OR gradual. May be stepwise (stable then sharp decline)

Question 11

SX VAcular Dementia

Answer 11

Symptoms are based on the part of brain affected.
 Complex thinking and planning, personality changes, agitation, and moodiness are more common early on than in AD
 Insight into deficits may be more preserved in vascular dementia vs. AD

Question 12

Describe Frontotemporal Dementia

Answer 12

o Strong genetic component and is earlier onset (40-50s)
o Damage is initially limited to frontal and temporal lobes. Over time, progresses to global impairment
 Changes in speech and personality occur before memory changes

Question 13

Describe PArkinson’s Dementia

Answer 13

o Dementia that develops after a clinical diagnosis of Parkinson disease
o Impairment in attention, visuospatial skills, and planning and completing complex tasks occurs early on
o Dopaminergic treatments for PD may exacerbate behavioural and psychological symptoms of dementia

Question 14

Describe LEWY Body Dementoa

Answer 14

o Lewy bodies: abnormal deposits of alpha-synuclein protein in neurons
o “Parkinson disease in reverse:” present with cognitive impairment and visual hallucinations first, or concurrently with PD motor symptoms
 Early postural instability and repeated falls are common
 Pronounced fluctuations
 Extremely sensitive to antipsychotics

Question 15

Diagnosis of Dementia

Answer 15

• Diagnoses: based on diagnosis of exclusion

o Neuroimaging may be supportive
o Rule out reversible causes for cognitive changes
o Detailed history to assess functional status (individuals may or may not have insight)
o Cognitive assessment

Question 16

Cognitive Assesments

Answer 16

 Mini-Mental Status Examination (MMSE): assesses multiple cognitive domains in ~ 10 minutes. Highly sensitive and specific to dementia, but not to mild cognitive impairment. Scores are affected by level of educational attainment. Lower score = more impairment.

Functional Activities Questionnaire (FAQ): developed to assess functional impairment, therefore needs to correlate with baseline function. Developed to be completed by a caregiver or close support. Higher score = poorer function.

Question 17

What is BPSD

Answer 17

• Behavioural and Psychological Symptoms of Dementia (BPSD): non-cognitive symptoms of disturbed thoughts, perception, mood, or behaviour, that may occur with dementia

Question 18

Describe Sx of BPSD

Answer 18

o Behavioral: agitation, aggression, wandering, disinhibition, repetitive behaviours, hoarding, vocalizations, nocturnal restlessness
o Psychological: apathy, emotional lability, paranoia, hallucinations, delusions, involuntary laughing/crying, depression

Question 19

Triggers of BPSD

Answer 19

 Psychological (fear of danger or being abandoned)
 Environmental (not liking who is around them)
 Medical (pain, constipation, hunger)
 Medication (anticholinergics, benzos, opioids, cannabinoids, anticonvulsants, fluoroquinolones, clarithromycin, psychoactive NSAIDs)

Question 20

Cholinesterase Inhibitor Examples

Answer 20

• Cholinesterase inhibitors: donepezil, galantamine, rivastigmine

Question 21

Cholinesterase MOA

Answer 21

o MOA: prevents the breakdown of acetylcholine

Question 22

Cholinesterase Inhbitors Effecr

Answer 22

o May show small improvements in measures of cognitions, but less likely to see improvements in functional abilities (1 in 42)
o May slow progression (1 in 12)
 Seen in 3-6 months if there is a benefit (EDS criteria – MMSE, FAQ)

Question 23

Cholinesterase Indication

Answer 23

o Indication: mild to severe Alzheimer’s

Question 24

Side Effects Cholinesterase Inhibitors

Answer 24

o Side effects: dose related
 Common: N/V/D, loss of appetite, insomnia, urinary urgency +/- incontinence
 Less common: weight loss, agitation, bradycardia, syncope, GI bleed, behaviour disturbances, nightmares, QT prolongation (donepezil and galantamine)

Question 25

Cholinesterase CI and CAutions

Answer 25

o Contraindications: uncontrolled/severe asthma or COPD, cardiac conduction abnormalities, bradycardia (< 55 bpm)
o Precautions: ulcers, uncontrolled GERD, urinary incontinence, seizure history, current anticholinergics (EDS)

Question 26

NDMA ANtgonist Examples

Answer 26

• NMDA antagonist: memantine

Question 27

NDMA MOA

Answer 27

o MOA: blocks glutamate at NMDA receptor

Question 28

NDMA Effect

Answer 28

o Can be combined with cholinesterase inhibitor, but unknown benefit
o Benefits seen in cognitive testing, but minimal clinical benefit in most cases

Question 29

Indication NDMA

Answer 29

o Indication: moderate to severe Alzheimer’s

Question 30

Side Effects NDMA and Cuation

Answer 30

o Side effects: better tolerated than cholinesterase inhibitors
 Dizziness, constipation, confusion, insomnia, headache, hypertension, restlessness, akathisia, nausea, QT prolongation
o Precautions: cardiovascular disease or seizures
o Must renal adjust

Question 31

TX Discontinuation Dementia

Answer 31

o When the situation progresses to risk>benefit (adverse effects)
o When loss of ability to perform ADLs independently i.e., no meaningful benefit remaining
o Taper at least over 2-4 weeks

Question 32

Monoclonal ANtibodies Dementia

Answer 32

o Current drugs may decrease symptoms, but new “-mab” drugs were developed to be disease-modifying
o Unclear clinical significance: CLARITY-AD trial showed that Lecanemab slowed cognitive decline by 27% over placebo.

Question 33

Monoclonal Antibodies Avilable Dementia

Answer 33

o Lecanemab
 MOA: reduces beta-amyloid plaques in the brain
 Indication: mild cognitive impairment or mild AD
 Formulation: IV q2weeks
 Significant risk for adverse effects: brain bleeding and/or swelling
 Currently under review by Health Canada
o Donanemab
 Formulation: IV monthly x 18 months

Question 34

TX BPSD

Answer 34

Question 35

What sx of bPSD are ammendable to pharmacotx?

Answer 35

Aggression (may be verbal or physical)*
Paranoia
Hallucinations
Delusions
Depression

Question 36

Antidepressants BPSD

Answer 36

Citalopram, escitalopram, sertraline, venlafaxine, duloxetine, mirtazapine, bupropion

Avoid TCAs and paroxetine (anticholinergic)

Avoid fluoxetine (Drug interactions, longer t1/2)

Question 37

When to use antidepressants in BPSD?

Answer 37

When depression or anxiety is root trigger of behaviour

Daily if for depression or chronic anxiety

If sleep is a significant issue – mirtazapine or trazodone may be preferred (avoid Z drugs)

AVOID benzodiazepines for anxiety or for sedation!

Question 38

Why should BZD’s be avoided in BPSD?

Answer 38

Worsen cognitive impairment, ↑ fall risk, may also worsen disinhibition

Occasionally may be used short-term following a stressful event (e.g. change in residence, bereavement) OR preventatively before dental work, etc.

Low dose of short half-life benzodiazepine, e.g. lorazepam 0.5 mg as a single dose

Question 39

Antipsychotics BPSD

Answer 39

Risperidone*, olanzapine, quetiapine, aripiprazole, clozapine, haloperidol (delirium)

Atypical preferred (decreased EPS, older adults more susceptible to developing EPS)

Given only if behaviour is causing harm and/or has not responded to non-pharmacological methods

Black box warning: ↑ risk of mortality (1.2-1.6x)

Try to taper and stop every 3 months

Question 40

Risk of Antipsychotics

Answer 40

Watch for: weight gain, ↓BP (orthostatic hypotension), anticholinergic effects, sedation, falls, EPS, tardive dyskinesia, urinary retention
MUST be followed, monitored, and removed if necessary
START LOW, GO SLOW (↑ and ↓)

Question 41

decision of which anti-psychotics

Answer 41

No atypical antipsychotics better than another –> Pick something based off of side effects profile

Olanzapine not used in older adults (anticholinergic effects)
Quetiapine and Risperidone are main ones used
Quetiapine less DA blocking effects (EPS), more sedation
Risperidone is the only one that has an on-label indication for BPSD

Question 42

Haloperidol BPSD

Answer 42

Haloperidol to manage acute delirium – PRN only

Not recommended in Parkinson’s patients due to extra-pyramidal symptoms (EPS)

Question 43

Apathy Management BPSD

Answer 43

Generally risk&raquo_space; benefit!
Stimulants
Sedatives

Question 44

Methylephenidate

Answer 44

Question 45

Sedtaives

Answer 45

Question 46

Analgesics

Answer 46