Managing dementia and cognitive enhancers

Dementia is a progressive neurological condition.

This hot topic considers the appropriateness of therapy (acetylcholinesterase inhibitors (AChEI) and memantine) to manage dementia.

Medication can provide modest improvements in attention and function for people with dementia. They are generally well-tolerated, and most adverse effects are short-lived, and some can be managed with practical advice.

A thorough clinical assessment including delirium screening should be completed if there is increasing confusion, hallucinations, stress and distress behaviours. Review and consider environmental, social, physical and medication changes and other stressors such as acute intercurrent illness, pain, constipation. Include a review of all medicines with anticholinergic effects. Any changes or causes should be managed prior to initiating medication.

• There is a good evidence base for non-pharmacological treatments to improve quality of life in all types of dementia.^133,235
• The AChEI donepezil, rivastigmine and galantamine and the N-methyl-D-aspartate (NMDA) receptor antagonist, memantine can be an important part of the individual’s treatment to manage symptoms of dementia.
• The evidence supports a delay in progression to 24-hour care from treatment with this group of medicines.²³⁶
• Cognitive enhancers do not delay the underlying progression of dementia. However, stopping established treatment may lead to loss of cognition or function which may not be regained if the medication is restarted. Current guidance emphasises that the medicines should not be stopped based on disease severity alone,²³⁶ as continuing benefits in function and reduction of stress and distress can be seen, even in severe disease. Therefore, the risks and benefits of deprescribing should be considered carefully.
• Initiating and reviewing these medicines is a specialist role and includes relevant post diagnostic support (for Scotland see the Dementia Strategy for Scotland).²³⁷ It is important to understand the principles of prescribing the medicines and situations where a therapeutic trial of medication may be appropriate.

Dementia medication licensed and unlicensed indications

Please note that the table below may need to be scrolled horizontally or vertically in order to view all information, depending on your device.

General considerations prior to commencing medication:

• Increasing confusion, hallucinations, stress and distress behaviours, should prompt a thorough clinical assessment including delirium screening, review of environmental, social, physical and other stressors, and review of all medicines with anticholinergic effects
• Acute intercurrent illness, pain, constipation or a change in environment or care, can precipitate increasing confusion and those causes should be managed²³⁹
• Recent changes in doses, starting or stopping medicines for dementia can precipitate changes in symptoms or function

Benefits:

• These medicines have a modest effect on symptoms which may still be significant for individuals
• For those with dementia who have symptoms of stress and distress, memantine can be used as an add-on treatment. It is also an option for people who do not tolerate AChEI, or where disease progresses despite their use

Risks:

• When assessing disease severity, consider factors that could affect the assessment and interpretation of cognition¹³³
  • physical, sensory or learning disabilities
  • communication difficulties
  • cultural or language differences
• Previously tolerated medication can cause problems as dementia progresses and people become more sensitive to adverse drug reactions
• Specific side effects such as bradycardia or gastrointestinal side effects are known risks
• For a person with dementia in severe distress, where other causes have been excluded, there may be a role for discussing with individual or (carer/ next of kin/ welfare power of attorney) whether a therapeutic trial of stopping AChEI or memantine is warranted. It is not recommended to withdraw AChEI/ memantine unless this is the cause of SSDD, and the risks of doing this need to be discussed.¹³³

• Once initiated, effectiveness of these medicines should be assessed in partnership with the individual and their representatives, and this assessment must be holistic. Consider what matters to them in terms of perceived benefit/stability and severity of side effects
• Indicators that may help inform decisions to continue or stop therapy include:
  • rate of cognitive decline
  • global presentation
  • functional ability
  • and/or reduction of behavioural symptoms of stress and distress

Standardised tests (e.g. mini mental state examination (MMSE)) may be undertaken to help inform decisions but should not be the sole driver for change. For example, deterioration from moderate to severe disease should not automatically result in medicines licensed for mild to moderate symptoms being withdrawn, as continuing benefits in function and reduction of stress and distress can be seen.

• Stopping established treatment may lead to loss of cognition or function which may not be regained if the medication is restarted, so the risks and benefits of deprescribing should be considered carefully²³⁶
• For intolerance of one AChEI, a switch to a second can be considered after the adverse effects have resolved. Adverse effects usually settle within a few days. Switching advice can be sought from specialists

Acetylcholinesterase inhibitors

Gastrointestinal (GI) side effects

• These are common and can lead to weight loss. Review should include weight monitoring to highlight potential GI adverse effects
• Most occur soon after starting the medication and quickly subside
• New medicines to treat GI symptoms should be avoided with practical approaches being tried first, such as dose reduction or advice about eating small amounts more often
• For a person who is losing weight while on an AChEI (where other causes of weight loss have been excluded), a trial without the medication may be indicated, however this has the associated risk of loss of other functional abilities and so the decision must be carefully balanced

Cardiac conduction abnormalities

There is no consensus guidance on when to specifically stop. The risks and benefits of treatment should be assessed with the individual and/or carers.

Cardiac conditions that require caution when considering prescribing AChEI:

• second or third-degree heart block in a person without a pacemaker
• QT prolongation
• bradycardia of less than 50 beats per minute
• left bundle branch block
• trifascicular block

Review appropriateness of ongoing AChEI use should these conditions develop:

• any second-degree heart block
• third-degree heart block
• trifascicular block
• significant bradycardia (whether sinus or junctional – heart rate (HR) <50bpm), but if symptoms (dizzy turns/falls) then HR <60bpm

Assessment of radial pulse and blood pressure is recommended during medication review or in individuals who may be experiencing any of the cardiac conduction adverse drug effects. Falls/syncope, breathlessness or dizziness should prompt measurement of radial pulse and blood pressure.

Prescribe AChEI cautiously if pulse is between 50-60bpm and asymptomatic.

Other medicines that can cause bradycardia should be taken into consideration when prescribing AChEI:

• individuals on medicines such as beta-blockers, amiodarone, digoxin, rate-limiting calcium channel blockers (e.g. diltiazem, verapamil)
• if rate-limiting calcium channel blockers or beta-blockers are being used to treat hypertension, alternative antihypertensive agents might be considered to facilitate the introduction or continuation of AChEI

Although there are known cardiac side effects of AChEI, there is a trend towards better cardiac outcomes for people prescribed these.²³⁸

Memantine

• Memantine may enhance the effects of anticholinergics, L-dopa and dopaminergic agonists and this should be taken into consideration when reviewing medication. As with other medicines, memantine may be less well tolerated as dementia progresses and people may become more sensitive to side effects

Where people do not tolerate these medicines due to side effects, it is appropriate to stop the medication.

• Discontinuing AChEI in those with dementia may result in a decline of cognitive function and greater functional impairment. It may be appropriate to discontinue when:
• the individual is sufficiently non-adherent with the medication that continued prescription of it would not be worthwhile
• Covert medication usage may mean AChEI are not prioritised. However, at the first sign of a significant deterioration after a therapeutic trial of stopping, consider a restart where the benefits of the treatment outweigh the risks
• intolerable side effects experienced such as significant weight loss or increased agitation where the risks outweigh the benefits. The transdermal route may not resolve GI issues and if a trial of this shows no improvement, then consider stopping
• emerging comorbidities make the risk of continued use either unacceptable or futile (e.g. concurrent physical illness with contra-indications); or
• the individual's dementia or other conditions progress to a stage where there would be no clinically meaningful benefit from continued therapy (e.g. approaching end of life care due to dementia or another life-limiting condition)
• an individual and/or their welfare power of attorney and/or welfare guardian decide to stop after being appraised of the risks and benefits of continuation and discontinuation

How to stop:

• it is reasonable to reduce the dose for one week and then stop
• review within two weeks to ensure there has been either an improvement in symptoms of stress or distress, or no deterioration in functional ability
• if medication is restarted within two weeks there is less likelihood of irrecoverable loss of function
• acute illness may require immediate stop (e.g. if symptomatic bradycardia stopping donepezil 10mg may be preferable to reducing to 5mg)

Supporting people who do not or cannot reduce/stop

Stopping established treatment may lead to loss of cognition or function which may not be regained if the medication is restarted. Current guidance emphasises that the medicines should not be stopped based on disease severity alone, as continuing benefits in function and reduction of stress and distress can be seen, even in severe disease. Therefore, the risks and benefits of deprescribing should be considered carefully. By using a person-centred approach, consider the impact and expectations for disease progression for people with dementia and their carers before stopping medication. Consider the wishes of the person with dementia, where these can be articulated including their previous decisions regarding treatment.

Specific areas/situations where medication may need to be introduced or increased

Memantine can be introduced in addition to an AChEI without referral back to a specialist for a person with moderate or severe dementia.¹³³ Current practice may vary.

Residents of care homes may have undiagnosed dementia. Making a diagnosis can be helpful for many reasons such as consideration of legal frameworks for support with health and financial welfare. Consideration of all pharmacological and non-pharmacological treatment options should be made at the point of diagnosis.

Does the person understand the outcomes of the review, including risk and benefits?

• Discussion of medication choices with relevant welfare proxies (welfare power of attorney or welfare guardian) for people who lack capacity is essential to support collaborative decision-making
• The place of non-pharmacological interventions for stress and distress²³⁹

Is medication tailored to the individual?

• The condition itself (dementia) can impair adherence
• Strategies such as memory prompts, timers etc are available. Discuss with the individual, family and pharmacy team, what is achievable and likely to help
• Donepezil orodispersible tablets, memantine liquid and rivastigmine patches can be considered where there are swallowing difficulties that prevent use of plain tablets
• Where a person lacks capacity to decide whether to take medicines, consideration can be made to administer medicines covertly. Relevant best practice guidance should be followed²⁴⁰

Agree the plan

• Information for patients (and carers if appropriate) can be found on Alzheimer Scotland website²⁴¹ and the Choice and Medication website.²⁴² This includes information leaflets in a variety of formats about the medicines individually, and a ‘Handy Chart’ comparing the medicines for dementia²⁴³
• Other areas of life are affected by a diagnosis of dementia and in particular:
  • driving recommendations will be required as per DVLA guidance
  • early consideration by people with dementia of legal frameworks to support decision-making can save time (and money) later, e.g. financial and/or welfare power of attorney
  • future planning such as Anticipatory Care can be considered at any stage
• Additional support can include:
  • maintenance of wellbeing - eating prompts; medication prompts
  • maintenance of personal safety if living at home, e.g. fire/gas appliance safety

• self-management/support tools
• decision aids

The Choice and Medication website Handy Chart can be used to compare the medicines for dementia.²⁴³