Pharmacological mx of dementia

Question 1

Dementia

Answer 1

An umbrella term that describes a collection of symptoms that are caused by disorders affecting thinking, behaviour and the ability to perform every day tasks.

Question 2

NICE guidelines for providing information at diagnosis

Answer 2

dementia subtype
changes to expect as the disease progresses
which healthcare professionals will be involved in their care
support groups
research studies
driving

Question 3

interventions to promote cognition, independence and wellbeing

Answer 3

offer stimulation therapy for mild to moderate dementia
consider group reminiscence therapy for mild to moderate dementia

Question 4

interventions that should not be offered to promote cognition, independence and wellbeing

Answer 4

acupuncture
homeopathic remedies
cognitive training for mild to moderate alzheimer’s disease
interpersonal therapy
non invasive brain stimulation (unless as part of a randomised controlled trial)

Question 5

which have been found to not be effective to slow the progression of alzheimer’s disease

unless as part of a randomised controlled trial

Answer 5

diabetes medication
hypertension medicines
non-steroidal anti-inflammatory drugs (inc. aspirin)
statins

Question 6

acetylcholinesterase inhibitors (AChE)

Answer 6

donepizil (selective AChE inhibitor)
rivastigmine (non competitive inhibitor)
galantamine (competitive inhibitor)

Question 7

cholinergic depletion therapy

Answer 7

tx aimed at counteracting the loss of cholinergic neurons e.g. acetylcholinesterase inhibitors

Question 8

Perera et al. 2014 MMSE

Answer 8

mmse as a predictor of mortality in older adults referred to secondary mental healthcare
alzheimer’s vs. depression and others
lower MMSE scores associated with higher mortality regardless of dementia dx
HR 1.42 for people with lower cognitive function

Question 9

what is the threshold effect for the relationship between mmse score and mortality

Answer 9

mmse scores below 20 were associated with marked increase in mortality risk particularly in older patients with depression

Question 10

what is the efficacy of AChE inhibitors

Answer 10

modest benefit to reduce symptoms in dementias
1/3 intermittently better, 1/3 don’t get worse, 1/3 no benefit
non-curative, modifying or reversible
modest benefit to cognitive, functional and global symptamology scores
most benefit seen in mild to moderate alzheimer’s or dementia with lewy bodies
greater benefits in lewy body dementia (plus vascular dementia) vs alzheimer’s

Question 11

comments on the effect size of donepezil

Answer 11

the effect size of donepezil on cognitive function, functional capacity and global symptomatology is comparable to exercise

Question 12

Donepezil for agitation Howerd et al 2007

Answer 12

effectiveness of donepezil to treat agitation in alzheimer’s vs placebo
no significant difference in agitation reduction between donepezil vs placebo
donepezil found not to improve agitation in patients who didn’t response to non pharmacological interventions
donepezil should not be routinely used to manage agitation in alzheimer’s

Question 13

adverse effects of ache/ donepezil

Answer 13

adverse effects are predictable based on the known effects of excess choline
excess cholinergic stimulation associeted with nausea and vomiting, dizziness, insomnia and diarrhoea
the speed of titration affects plasma peaks therefore pathces are a better route of administration and slower titration is better to reduce side effects

Question 14

what is the tolerability of different AChE inhibitors

Answer 14

Mueller et al. 2017 conducted a meta analysis
rivastigmine is associated with higher rates of all cause discontinuation compared to other AChEI
mortality of AChE inhibitors is lower compared to placebo
adverse effects predictable based on cholinergic stimulation e.g nausea, insomnia etc
transdermal patches and slower titration reduce side effect

Question 15

cardiovascular effects of AChEI

Answer 15

precitable based on pharmacology
vagotonic effects on heart rate leading to bradycardia
especially problematin in patients with problems with conduction (heart) e.g. AV block/ SA block/ sick sinus
worst mortality effects seen with galanatamine

Question 16

why should treatment not be switched/ interrupted

Answer 16

interruptions to therapy are associated with a loss of irrecoverable benefits

Question 17

which AChEI is a NMDA receptor antagonist

Answer 17

Memantine

Question 18

memantine

Answer 18

a glutamate receptor antagonist; glutatmate inhibition is mediated by blocking NMDA-mediated ion influx

Question 19

which people benefit from mematine

Answer 19

there is a small benefit of memantine in moderate to severe alzheimer’s but not mild

Question 20

AChEI tolerability in mild to moderate vascular dementia

Answer 20

small clinical benefit of AChEI on cognitive function
small clinical benefit on behaviour and mood
no difference in activities of daily living
no difference in discontinuation

Question 21

AChEI may be slightly (very small certainty) efficacious in which other types of dementia

Answer 21

parkinson’s disease
frontotemporal dementia
aids related dementia complex

Question 22

is memantine a AChEI

Answer 22

No

it is an NMDA receptor antagonist

Question 23

domino trial

Answer 23

effects of donepezil and memantine in moderate to severe alzheimer’s
patients on donepezil for at least 3 months
continued treatment
stopped treatment
stopped and switched to memantine
continued donepezil and added memantine
findings
continuing donepezil provided cognitive benefits and maintained daily activites
memantine alone not significantly advantageous over donepezil
combination therapy not additionally advantageous vs. donepezil alone

Question 24

prescribing guidelines

Answer 24

AChEI or memantice can be started in primary care
memantine can be started in primary care for patients with an established AD dx already on an AChEI without consulting a specialist
can’t stop AChEI in AD patients based on severity only

Question 25

rivastigmine and memantine metabolism

Answer 25

non hepatic, this means that metabolism occurs extrahepatically missing the first pass effect, thus influencing bio availability

Question 26

which drugs have the opposite effect to AChEI

Answer 26

anticholiergic drugs | do not prescribe acnticholinergic drugs and AChEI together

Question 27

AEC scale

Answer 27

anticholinergic effect on cognition scale

Question 28

anticholinergic drugs

Answer 28

increase the risk of incident cognitive impairment and cognitive decline in older populations generally decrease physical functioning in older pop. generally unkown effects on delirium and mortality in dementia is a risk factor for psychosis in alzheimer's may increase rate of cognitive decline

Question 29

how is the AEC score determined

Answer 29

in vitro anticholinergic potency capacity to cross the blood-brain barrier receptor selectivity reported effects on cognitive impairment

Question 30

AEC scoring

Answer 30

0: safe to use (159) 1: caution required (34) 2: review and withdraw/ switch (19) 3: review and withdraw/ switch (21) | (number of drugs with associated score) ## Footnote papers to review Bishara et al 2020; 2021in JAMDA

Question 31

online medications adverse effects support tools

Answer 31

medichec

Question 32

bpsd

Answer 32

behavioural and psychological symptoms in dementia

Question 33

prevalence of bpsd

Answer 33

50-80%

Question 34

what percentage of bpsd are self limiting

Answer 34

50%

Question 35

how do you record bpsd

Answer 35

abc charts

Question 36

non pharmacological tx

Answer 36

person centered care aromatherapy multi sensory rooms music dance massage animal assisted therapy

Question 37

delphi consensus recommendations for mx agitation and neuropsychiatric symptoms in dementias

Answer 37

thourough ax and mx of underlying causes caregiver information and education environmental adaptations person centered care tailored activity programme citalopram treat pain risperidone

Question 38

delphi consensus recommendations for mx psychosis in dementias

Answer 38

thorough ax and mx of underlying causes risperidone (pimavanserin and citalopram emerging tx)

Question 39

principles of pharmacological tx

Answer 39

target symptoms low doses regular reviews monitor for side effects

Question 40

mx pain to help with bpsd in alzheimer's

Answer 40

systematic pain mx to reduce bpsd paracetamol as first line for mild to moderate pain morphine for moderate to severe pain buprenorphine transdermal path for continuous pain mx in pt with dysphagia oral pregabalin for neuropathic pain (nerve damage) systematic pain tx significantly improves agitation, neuropsychiatric symptoms and pain in dementia pt

Question 41

evidence related to antipsychotic use in bpsd

Answer 41

small effect sizes tartget symptoms better response in severe cases responses are quick - discontinue after 4-6 weeks best evidence in support of risperidone substantial risk of harm

Question 42

antipsychotic side effects

Answer 42

extrapyramidal symptoms gait disturbance somnolence respiratory tract infections fever peripheral oedema

Question 43

symptoms that antipsychotics do not help with

Answer 43

distress and anxiety during personal care repetitive vocalisations walking about social withdrawal changes in levels of inhibition

Question 44

how many people have a stroke whether they take an antipsychotic or not

Answer 44

8 | 6-12 weeks

Question 44

how many people have a stroke because they take an antipsychotics

Answer 44

12 | 6 -12 weeks

Question 45

how many people die whether or not they take an antipsychotic

Answer 45

22

Question 46

how many people die because they take an antipsychotic

Answer 46

11

Question 47

which factors increase antipsychotic-related mortality

Answer 47

male younger age at dementia dx severe dementia symptoms low frailty score index number of comorbid somatic conditions comorbid psychiatric conditions polypharmacotherapy drug interactions

Question 48

which factors are associated with lower mortality

Answer 48

depression and delusion in pt with agitation on risperidone monotherapy

Question 49

what are the implications for using antipsychotics in older adults with dementia

Answer 49

antipsychotics can resude bpsd however no medications are safe increased risk of mortality increased risk of cerebrovascular events extrapyramidal symptoms risks higher at beginning of treatment and remain high throughout higher rates of hospital admission, long term care and care home admission not very cost efficient physical health monitoring

Question 50

advantages of withdrawing antipsychotics as soon as able

Answer 50

improve long term survival not aassociated with relapse of bpsd slightly more preferable to other psychotropic medications

Question 51

what are some alternatives to antipsychotics to manage bpsd?

Answer 51

pimavanserine citalopram mirtazapine nabilone dextromethorpan/ quinidine

Question 52

# antipsychotic alternatives pimavanserine for psychosis in alzheimer's | ballard et al 2018 ## Footnote safety, tolerability, efficacy

Answer 52

randomised placebo-controlled double blind trial chage in npi-nuring home version score psychosis score at 6 weeks pimavanserine associated with significant reduction in psychosis symptoms vs placebo but not as 12 weeks pimavanserine is well tolerated tx does not cuase major cognitive or motor side effects longer trail needed

Question 53

# antipsychotic alternatives pimavanserine to prevent relapse in dementia psychosis | tariot et al 2021

Answer 53

phase 3 randomised double blind discontinuation trial alzheimer's, parkinsons disease dementia, dementia with lewy bodies, frontotemporal dementia, vascular dementia open label pimavanserine for 12 weeks ps who showed sustained imrovement randomsed to continue or switch to placebo for up to 26 weeks primary outcome: psychosis relapse

Question 53

# antipsychotic alternatives rates of psychosis relapse in dementia | tariot et al 2021 cont.

Answer 53

13% ps who continued pimavanserin relapsed vs 28% in placebo group study terminated early **significant hazard ratio 0.35** no significant cognitive or motor side effects **pimavanserin significantly resuces risk of psychosis relapse in dementia**

Question 54

# antipsychotic alternatives citalopram | citad trial citalopram for agitation in alzheimer's dementia ## Footnote efficacy, safety

Answer 54

randomised placebo controlled trial standardises psychosocial intervention to manage agitation still symptomatic pt randomised to psychological intervention plus citalopram vs placebo nine weeks primary outcome: changes in agitation on rating scale e.g. npi, cmai secondary outcomes: overall behavioural symptoms, caregiver distress, safety/ tolerability

Question 55

citalopram pt 2

Answer 55

**statistically significant improvement in agitation vs placebo but not npi agitation subscale** improvements on caregiver sistress and global measures side effects included prolonged QT interval prolongation and worsening cognition after nine weeks less delusions, anxiety, irritability/ lability hallucinations significantly decreased on npi

Question 56

mirtazapine for agitation in dementia | symbad trial

Answer 56

probable or possible alzheimer's with significant agitation unresponsive to non pharma tx cmai score more than or equal to 45 mirtzapine vs placebo reduction in agitation on the cmai at 12 weeks **no statistically significant difference between mirtazapine vs placebo at 12 weeks** increased mortality in mirtazapine group

Question 57

nabilone | synthetic cannabinoid

Answer 57

typically used as antiemetic in chemotherapy/ adjunct for neuropathic pain improvement in cmai, npi total score and npi-caregiver distress and mmse side effect: sedation reducing the dose or discontinuing leads to recurrence of agitation

Question 58

which measures can be used for bpsd

Answer 58

neuropsychiatric inventory cohen-mansfield agitation invetory (cmai)

Question 59

symptoms of depression and apathy

Answer 59

reduced interest in activities psychomotor retardation fatigue hypersomnia lack of insight

Question 60

depression (only) symptoms

Answer 60

pessimism hopelessness self-criticism feelings of guilt dysmorphia suicidal ideation

Question 61

apathy

Answer 61

a syndrome of primary motivational loss that is not attributable to emotional distress, intellectual impairment or diminished level of conciousness lack of motication characterised by dimished goal directed behaviour and cognition, and a diminished emotional connection to goal directed behaviour

Question 62

antidepressants in dementia | sertraline and mirtazapine ## Footnote banarjee et al 2011

Answer 62

hta-sadd trial cornell scale for depression in dementia (8 or more) sertraline vs mirtazapine vs placebo plus standard care primary outcome: reducedtion in depression severity at 13 weeks (changes in csdd) follow up at 39 weeks reductions in all groups **no statistically significant difference between any groups at 13 and 39 weeks** greater side effects associated with ertraline/ mirtazapine similar mortality

Question 63

non pharmacological mx of apathy

Answer 63

multisensory stimulation cognitive stimulation tailored therapuetic mentaally stimulating activities music therapy pet therapy behavioural activation physical therapy and exercise

Question 63

pharmacological mx of apathy

Answer 63

AChEI review antidepressants/ antipsychotics memantine methylphenidate/ stimulants ginkgo biloba

Question 64

tx for psychosis in pdd

Answer 64

investigate underlying mechanisms reduce/ discontinue non pd related psychoative tx reduce/ discont. pd medications add pimavanserin or quetiapine no improvement on pimavanserine add quetiapine for persisting hallucinations replace quetiapine with clozapine

Question 65

tx for psychosis in lewy body dementia

Answer 65

investigate underlying mechanisms reduce/ discontinue non pd related psychoative tx reduce/ discont. pd medications add AChEI for persisting hallucinations pimavanserine or quetiapine (or combination) for still persisting hallucinations replace quetiapine with clozapine

Question 66

which order should parkinson's disease medications be reduced (psychosis tx)

Answer 66

anticholinergics amantadine dopamine agonists MAO-b inhibitors COMT inhibitors levodopa