dementia

Question 1

non-modifiable risk factors for dementia

Answer 1

1) elderly
2) female
3) ethnicity: black, hispanic
4) genetics

• apolipoprotein E (APOE4) gene
• not routinely tested unless presence of family history

Question 2

modifiable risk factors for dementia

Answer 2

1) HTN, DM
2) binge drinking, smoking
3) limited physical activities
4) obesity
5) hearing loss
6) depression

Question 3

pathophysiology of dementia

Answer 3

1) senile plaques

• cleavage of amyloid precursor protein (APP) by beta and gamma secretases
• form beta-amyloid peptides that are sticky -> beta-amyloid plaque aggregates -> senile plaques -> very inflamamtory -> neuron apoptosis

2) neurofibrillary tangles

• presence of senile plaques -> hyperphosphorylation of tau protein -> assembly of paired helical filaments (PHF)
• Tau proteins required for microtubule stabilisation and intracellular transport
• formation of PHF -> neuron apoptosis

3) brain atrophy and neurodegeneration

• apoptosis involved in multiple neurotransmitter system (cholinergic, serotonergic, glutaminergic) -> neurochemical deficit and alterations -> cognitive decline and neuropsychiatric behaviours
• apoptosis in areas critical for cognition in brain (cortex, hippocampus)

Question 4

DSM-5 for dementia (major neurodegenerative disorder)

Answer 4

1) evidence of significant cognitive decline from prior level of performance in 1/> cognitive domains from baseline

• complex attention, executive function, learning and memory, language, perceptual-motor or social cognition
• concerns regarding this significant decline
• substantial impairment in cognitive performance

2) cognitive deficit interfere with independence of everyday activities
3) cognitive deficits not due to delirium
4) cognitive deficits not better explained by another mental disorder

Question 5

DSM-5 criteria for dementia (minor neurodegenerative disorder)

Answer 5

1) evidence of modest cognitive decline from prior level of performance in one or more cognitive domains
2) cognitive deficit interfere with independence of everyday activities
3) cognitive deficit not due to delirium
4) cognitive deficit not better explained by another mental disorder

Question 6

clinical presentation of early stage dementia

Answer 6

1) cognitive

• short term memory loss, word finding difficulties

2) psychological

• apathy, depressive symptoms

3) behavioural

• social withdrawal, disinhibition

4) sleep

• REM behaviour disorder

5) physical

• gait impairment

Question 7

clinical presentation of late stage dementia

Answer 7

1) cognitive

• memory loss, more marked expressive difficulties and eventual loss of language

2) psychological

• delusions, anosognosia (not aware of dementia)

3) behavioural

• aggression, hallucination, wandering

4) sleep

• altered sleep-wake cycle

5) physical

• reptitive purposeless movement, parkinsonism, seizure

Question 8

diagnosis of dementia tldr

Answer 8

1) mini MSE
2) montreal cognitive assessment (MoCA)
3) clinical evalutation

Question 9

diagnosis of dementia - mini MSE

Answer 9

• mild 20 - 40
• moderate 10 - 19
• severe < 10

Question 10

diagnosis of dementia - montreal cognitive assessment

Answer 10

• mild 18 - 25
• moderate 10 - 17
• severe < 10

Question 11

diagnosis of dementia - clinical evaluation

Answer 11

• med history
• cognitive examination
• neuropsychological testing if required
• physical examination
• lab testing (thyroid function, Vit B12)
• structural brain imaging w CT/MRI

Question 12

treatment algorithm for dementia

Answer 12

1) mild - moderate

• acetylcholinesterase inhibitor (AI) monotherapy

2) moderate and intolerant/CI to AI or severe

• memantine monotherapy

3) already on AI

• moderate: consider combination w memantine
• severe: start combination w memantine

Question 13

types of AI

Answer 13

1) donepezil
2) rivastigmine

• oral and transdermal patch
• shorter t1/2 than galantamine
• metabolised by kidney

3) galantamine

• oral tablet
• also act on nicotinic receptor in brain -> therapeutic effect
• metabolised in liver (CYP450)

Question 14

MOA of AI

Answer 14

inhibit acetylcholinesterases in synpase

• increase acetylcholine neurotransmission at synaptic cleft

Question 15

dosing regimen for AI

Answer 15

• slow titration regimen over 4 - 8 wks to reach target dose and minimise AE
• what to do if encounter AE
  ** lower dose temporarily before re-escalating more slowly and monitor for AE recurrence
  ** or discontinue drug and switch to other AI

Question 16

monitoring for AI

Answer 16

• good response = slight improvement in day to day life
• routine cognitive test
• switch to memantine if intolerable/X tolerate

Question 17

AI SE

Answer 17

• cholinergic hyperactivation -> activation of parasympathetic nervous system
  ** N/V, D, increased bowel movement
• less common
  ** muscle cramp, bradycardia, loss of appetite, increased gastric juice secretion

Question 18

AI caution

Answer 18

• starting donepezil w pre-existing bradycardia or meds that cause bradycardia

Question 19

NMDA receptor antagonist for dementia - types

Answer 19

memantine

Question 20

NMDA receptor antagonist for dementia - MOA

Answer 20

block NMDA receptor -> reduce excitotoxicity

Question 21

NMDA receptor antagonist for dementia - SE

Answer 21

hallucination, confusion, dizziness, headache

Question 22

lecanemab for dementia

Answer 22

• only coming to SG end 2024
• need to go through genotyping and phenotyping before initiation
• a lot of exclusion criteria to go through
• patient need IV infusion every few weeks
• AE: vasogenic oedema, small haemorrhage

Question 23

non pharmaco for dementia

Answer 23

1) cognitive stimulating activities
2) physical exercise
3) social interactions with others
4) health diet, adequate sleep
5) proper personal hygiene
6) safety inside and outside home
7) medical and advanced care directives (designation of power of attorney)
8) long term health care planning
9) financial planning
10) effective communications
11) psychological health (participate in personally meaningful activities)

Question 24

what is BPSD?

Answer 24

• spectrum of non-cognitive and non-neurological symptoms of dementia
  ** agitation, aggression, psychosis, depression, apathy
• often an attempt of patient to communicate, need to understand why behaviour is occurring

Question 25

contributing factors to BPSD

Answer 25

1) medical - depression, anxiety, delirium - untreated pain (uncommunicated, want to get attention) - infection, constipation, urinary retention - hearing/visual impairment 2) pharmacological - medication w anticholinergic effect - anticonvulsant - systemic corticosteroids (esp high dose) - med w sedative actions - anti PD meds 3) environmental/social - unfamiliar environment - lack of privacy, space, security

Question 26

framework for approaching BPSD first step

Answer 26

determine if BPSD or delirium

Question 27

framework for approaching BPSD - what to do if it is BPSD

Answer 27

1) examine and treat any causative problems 2) review if behavioural problems returned

Question 28

framework for approaching BPSD - confirmed BPSD - causative problems

Answer 28

1) physical problems (infection, pain, constipation) 2) activity related problems 3) intrinsic to dementia (wandering) 4) depression - consider SSRI/mirtazapine - monitor for hyponatremia and any initial increase in agitation 5) anxiety - consider SSRI - monitor for hyponatremia and any initial increase in agitation - if severe case and SSRI not useful -> benzodiazepine 6) insomnia - sleep hygiene - 2-3 wk trial short acting melatonin or hypnotic if melatonin CMI

Question 29

framework for approaching BPSD - confirmed BPSD - problems not returning after initial treatment

Answer 29

X further treatment required, X antipsychotic use

Question 30

framework for approaching BPSD - confirmed BPSD, problems return after initial treatment

Answer 30

1) non pharm 1st line 2) pharm - only when symptoms severe and pose risk to individual/others or when reversible causes excluded and non pharm trialed - short term and kept under close review - monitoring ** every 3 month, slowly taper dose after 3 month of improved BPSD, if recurrence then restart lowest effective dose ** SE and worsening cognitive function

Question 31

framework for approaching BPSD - confirmed BPSD, problems return after initial treatment - non pharm

Answer 31

1) full understanding of patient for patient centred approach 2) remove triggers of BPSD symptoms, provide calming environment 3) go back to patient pre-morbid routine and make small changes for patient to articulate their wishes 4) make dosage form/frequency simpler for caregivers 5) sundowning: make sure room well lit and free from shadows

Question 32

framework for approaching BPSD - confirmed BPSD, problems return after initial treatment - pharm treatment

Answer 32

1) AI/memantine if not already prescribed 2) SSRI - for depression and anxiety - citalopram reduce agitation and improve other symptoms like delusion 3) AVOID TCA 4) antipsychotics - help aggression, agitation, psychotic symptoms that are causing severe distress or an immediate risk of harm to patient or others - not helpful for BPSD (wandering, calling out, social withdrawal, inappropriate sexualised behaviour, challenges due to environmental triggers - X routinely used cuz of AE

Question 33

framework for approaching BPSD - confirmed delirium

Answer 33

- delirium symptoms ** short history of confusion, hallucination, delusion w fluctuating cognition - treat underlying acute medical conditions causing behavioural problems (UTI, drug SE, alc/drug withdrawal) - review if behavioural problems returned ** if X recurrence then X further treatment, X antipsychotic use ** if recurrence then non pharm approaches

Question 34

framework for approaching BPSD - neither delirium or BPSD

Answer 34

- check if patient treated for other neuropsychiatric problems ** if yes then follow guidelines for those problems