Pharmacological Management of Dementia Flashcards
What interventions could you offer to someone with mild to moderate dementia to promote cognition, independence and wellbeing?
▪️ Cognitive stimulation therapy
▪️ Group reminiscence therapy
What non-pharmacological interventions should NOT be offered to people with dementia?
▪️ Acupuncture
▪️ Vitamins and herbal supplements
▪️ Cognitive TRAINING
▪️ Interpersonal therapies for cognitive symptoms
▪️ Non-invasive brain stimulation (unless an RCT)
What medications should NOT be offered to people with AD to slow progression except if part of an RCT?
▪️ Diabetes medicine
▪️ Hypertension medicines
▪️ Statins
▪️ NSAIDs, including aspirin
What is the main class of medication used for symptomatic relief in dementia?
Acetylcholinesterase inhibitors
What are the main acetylcholinesterase inhibitors and what are their mechanisms of action?
▪️ Donepezil - selective inhibitor
▪️ Rivastigmine - non-competitive inhibitor
▪️ Galantamine - competitive inhibitor
Increase availability of acetylcholine in synapses
All reversible!
What is the theory behind the use of acetylcholinesterase inhibitors in AD?
The cholinergic deletion theory
▪️ Progressive loss of limbic and neocortical cholinergic innervation
▪️ Acetylcholine metabolism plays key role in cognition and memory processes
Why is galantamine use much less commonly in the UK?
Controversies over increased mortality in MCI and increased risk of cardiovascular effects
What is the efficacy of acetylcholinesterase inhibitors?
▪️ Essentially all the same with modest benefit
▪️ 1/3 get intermittently better, 1/3 don’t get worse
▪️ Modest benefit on cognitive, functional and global scores (only symptom control)
▪️ For mild-moderate dementia
How does dementia subtype influence response to AChEI treatment?
Moderates it
▪️ Best response = PDD and DLB, particularly with rivastigmine
▪️ Less improvement on MMS in AD and VaD
How does AChEI treatment affect neuropsychiatric symptoms?
▪️ No short-term benefit
▪️ Potentially less likely to get severe NP symptoms if started early?
What neuropsychiatric symptom can donepezil be considered for?
Agitation
BUT not a great effect and should try cognitive, behavioural, and psychological interventions first
What are the most common side effects of AChEI and why?
▪️ Nausea
▪️ Vomiting
▪️ Dizziness
▪️ Insomnia - can bring REM sleep forward
▪️ Diarrhoea
Usually early on due to excess cholinergic stimulation and increased amounts of acetylcholine in the synaptic cleft - takes time to get used to
Why might rivastigmine be associated with lower risk of adverse effects?
▪️ Can be given transdermally
▪️ Can titrate it to get used to it
▪️ Slow titration = reduced plasma peaks
▪️ Also no notable drug interactions
Which AChEI is associated with more all-cause discontinuation?
Rivastigmine
What is the effect of AChEI on mortality?
▪️ Decreased risk by 23%
▪️ BUT are those with higher risk unlikely to be given medication?
What cardiovascular side effect might someone experience on AChEI?
▪️ Vagotonic effects on heart rate causing bradycardia
▪️ Dizziness and syncope
▪️ Rare = atrial arrhythmias, MI, angina, seizures
What must you be careful of when starting someone of AChEI?
Prior conduction disturbances such as AV block, SA block or sick sinus
Ideally get an ECG before starting medications and check pulse routinely
What should you do if the patient has a heart rate below 50bpm?
Withhold or stop treatment of AChEI and refer on to specialist for underlying cause
If unrelated to drug or fitted with pacemaker, could consider retrial of drug
What should you do if someone cannot tolerate the side effects of an acetylcholinesterase inhibitor?
▪️ Ideally withdraw slowly, wait for side effects to stop, then start another drug
▪️ Avoid interrupting as may cause loss of benefits
What type of medication can be considered in the later stages of dementia and how do they work?
NMDA receptor antagonists such as memantine
Reduce glutamate by blocking NMDA-mediated ion flux - ‘calming the brain’
(best benefit in moderate-severe AD)
What side effects are associated with memantine?
▪️ Very few - possibly dizziness of headaches
▪️ Can make you drowsy which may be beneficial in late stages
▪️ So beneficial and benign it can be prescribed by GPs
▪️ Consider kidney health as excreted renally
What is the efficacy of memantine in other subtypes of dementia?
▪️ Small clinical benefit in mild-moderate VaD on cognition, behaviour, and mood
▪️ Limited efficacy in PDD, DLB, FTD, and AIDS-related Dementia Complex
What drug should you NOT prescribe alongside acetylcholinesterace inhibitors?
Anticholinergic drugs (e.g., clozapine, tricyclic antidepressants, atropine)
Why should anticholinergic medications be avoided in dementia?
▪️ Directly oppose action of AChEI
▪️ Greater risk of cognitive impairment and decreased physical functioning in elderly
▪️ Possible effects on delirium and mortality in elderly?
▪️ Risk factor for psychosis in AD and faster cognitive decline?
What is the Anticholinergic Effect on Cognition scale?
A score to advise prescribing, determined by:
▪️ anticholinergic potency
▪️ capacity to cross BBB
▪️ receptor selectivity
▪️ reports of cognitive impairment
0 = safe, 1 = caution, 2-3 = review and withdraw/switch
(Can add scores of multiple medications for total AEC score)
How does score on the AEC scale affect mortality and emergency hospitalisation?
No effect on either
What type of anticholinergic drug was found to be associated with increased emergency hospitalisation and cognitive decline?
Those for urinary conditions
Which types of anticholinergic drug are associated with increased mortality?
▪️ Antidepressants
▪️ Antipsychotics
How common are behavioural and psychological symptoms in dementia (BPSD)?
50-80%
▪️ More common earlier on in DLB
▪️ More common later in AD?
(50% = self-limiting)
What is the first step for treating BPSD?
Look for easily treatable cause
▪️ Sensory deficits
▪️ Pain, constipation, infections
▪️ Delirium
▪️ Medication side effects
(Use ABC chart!)
According to the Delphi consensus, what are the top 4 recommendations for agitation in dementia?
- Assessment of underlying cause
- Environmental adaptations
- Person centred care
- Tailored activity
(7 = risperidone)
(Also included citalopram and pain management low down)
What side effects are associated with use of antipsychotics in dementia?
▪️ Extrapyramidal symptoms
▪️ Gait disturbance
▪️ Somnolence
▪️ Respiratory tract infection
▪️ Fever
▪️ Peripheral oedema
▪️ Increased risk of stroke and death?
What is the evidence for antipsychotics in dementia?
▪️ Very limited evidence with small effect sizes and purely symptomatic
▪️ Better response in severe cases
▪️ Quick response (discontinue if no benefit in 4-6 weeks)
▪️ Risperidone is likely best
▪️ BUT substantial risk of harm
What is the evidence for the use of citalopram in dementia?
▪️ Improvements in CGIC, agitation, total NPI and caregiver distress
▪️ No improvement on NPI agitation subscale
▪️ Worsening cognition and QT interval prolongations = increased risk of cardiac issues
▪️ Best for psychosis in dementia - improved delusions, hallucinations, anxiety, and irritability
What alternatives to antipsychotics may be considered for agitation in dementia?
▪️ Citalopram
▪️ Mirtazapine
▪️ Pimavanserine
▪️ Dextromethorphan/quinidine
▪️ Pain management and analgesics
Cannabinoids - safer alternative?
What is the evidence for mirtazapine for agitation in dementia?
Agitation improves but no difference in benefit compared to placebo - role of engagement?
What might pimavanserine be useful for in dementia and why
Psychosis
Shows very good benefit in PD
What are the recommended treatments for psychosis in PDD and LBD?
▪️ Treat underlying cause or reduce PD medications
▪️ Significant benefit of clozapine
▪️ Possibly quetiapine
▪️ Olanzapine off label BUT associated with worse motor symptoms
What are the problems with prescribing clozapine for dementia?
▪️ Very anticholinergic
▪️ Associated with severe cardiac AEs such as agranulocytosis
▪️ Needs monitoring and regular blood tests
