Dementia

Introduction

NICE describes dementia in NG97: Dementia is a term used to describe a range of cognitive and behavioural symptoms that can include memory loss, problems with reasoning and communication and change in personality, and a reduction in a person’s ability to carry out daily activities, such as shopping, washing, dressing, and cooking. The most common types of dementia include Alzheimer’s disease, vascular dementia, mixed dementia, dementia with Lewy bodies and frontotemporal dementia. Dementia is a progressive condition, which means that the symptoms will gradually get worse. This progression will vary from person to person, and each will experience dementia in a different way – people may often have some of the same general symptoms, but the degree to which these affect each person will vary.

For people with an established diagnosis of Alzheimer’s disease who are already taking an AChE inhibitor, primary care prescribers may start treatment with memantine without taking advice from a specialist clinician if in accordance with NICE guidelines.

It is important to recognise that there is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes. Drug treatment for Alzheimer’s disease should form part of a wider package of support and information for the patient and their carer.

Be aware that some commonly prescribed medicines are associated with increased anticholinergic burden, and therefore cognitive impairment. Consider minimising the use of medicines associated with increased anticholinergic burden, and if possible, look for alternatives:

– when assessing whether to refer a person with suspected dementia for diagnosis

– during medication reviews with people living with dementia (NICE NG97)

Treatment with an AChE inhibitor or memantine should only be initiated if reasonable steps are taken to ensure adequate compliance.

Diagnosis

Further Information and Resources

Please click on the links below or visit:

https://bnf.nice.org.uk/

Dementia | Treatment summaries | BNF | NICE

http://www.medicines.org.uk/emc/

NICE TA217 Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease

NICE NG97 Dementia: assessment, management and support for people living with dementia and their carers

NG71 | Parkinson’s disease in adults | Guidance | NICE

See the NHS Somerset Deprescribing – NHS Somerset page for more information on anticholinergic burden.

Pharmacological Management by Disease Type

Disease type	AChE Inhibitor Monotherapy	Memantine Monotherapy	Combined AChE Inhibitor and Memantine Therapy
Alzheimer’s Disease	The three AChE inhibitors donepezil, galantamine and rivastigmine as monotherapies are recommended as options for managing mild to moderate Alzheimer’s disease	Memantine monotherapy is recommended as an option for managing Alzheimer’s disease for people with: -moderate Alzheimer’s disease who are intolerant of or have a contraindication to AChE inhibitors or -severe Alzheimer’s disease.	For people with an established diagnosis of Alzheimer’s disease who are already taking an AChE inhibitor: consider memantine in addition to an AChE inhibitor if they have moderate disease. Offer memantine in addition to an AChE inhibitor if they have severe disease.
Dementia with Lewy Bodies	Offer donepezil or rivastigmine to people with mild to moderate dementia with Lewy bodies. Only consider galantamine for people with mild to moderate dementia with Lewy bodies if donepezil and rivastigmine are not tolerated. Consider donepezil or rivastigmine for people with severe dementia with Lewy bodies.	Consider memantine for people with dementia with Lewy bodies if AChE inhibitors are not tolerated or are contraindicated.	Not recommended
Parkinson’s Disease Dementia NG71	Offer an AChE inhibitor for people with mild or moderate Parkinson’s disease dementia (NG71). Rivastigmine capsules are the only treatment with a UK marketing authorisation for this indication. Use of donepezil, galantamine and rivastigmine patches is off-label. Consider an AChE inhibitor (donepezil or rivastigmine) for people with severe Parkinson’s disease dementia. This is an off-label use of AChE inhibitors Specialist to always review antiparkinsonian and other medications first.	Consider memantine for people with Parkinson’s disease dementia, only if AChE inhibitors are not tolerated or are contraindicated. This is an off-label use of memantine. Specialist to always review antiparkinsonian and other medications first.	Not recommended Specialist to always review antiparkinsonian and other medications first.
Vascular Dementia	Only consider AChE inhibitors or memantine for people with vascular dementia if they have suspected comorbid (Severe) Alzheimer’s disease, Parkinson’s disease dementia or dementia with Lewy bodies.	Only consider AChE inhibitors or memantine for people with vascular dementia if they have suspected comorbid (Severe) Alzheimer’s disease, Parkinson’s disease dementia or dementia with Lewy bodies.	Not recommended

Frontotemporal Dementia (including behavioural variant, Semantic, Primary Progressive Aphasia and Pick’s disease)

Do not offer AChE inhibitors or memantine to people with frontotemporal dementia. Note that logopenic aphasia, which has previously been included in some diagnostic guidelines for frontotemporal dementia, has now been shown to most commonly be caused by Alzheimer’s disease, however Lewy b may be implicated in this symptom too. Medication should be considered by clinicians if these diseases are diagnosed.

Frontal-overlap syndromes (Cortico-basal Degeneration and Progressive supranuclear palsy) & Prion disease

Do not offer AChE inhibitors or memantine

Treatment Summary Table

Drug	Donepezil	Rivastigmine	Galantamine	Memantine
	See appropriate Summary of Product Characteristics	See appropriate Summary of Product Characteristics	See appropriate Summary of Product Characteristics	See appropriate Summary of Product Characteristics
Therapeutic Dose	Initially 5 mg once daily for one month, then increased if necessary up to 10 mg daily, doses to be given at bedtime Available as: tablet, orodispersible tablet, oral solution	Oral: Initially 1.5 mg twice daily, increased in steps of 1.5 mg twice daily, dose to be increased at intervals of at least 2 weeks according to response and tolerance; usual dose 3–6 mg twice daily (max. per dose 6 mg twice daily), if treatment interrupted for more than several days, re-titrate from 1.5 mg twice daily For dose conversion and equivalence when switching from oral to transdermal patch – see BNF or SmPC Available as: capsule, oral solution, transdermal patch	Immediate release tablet/oral solution: Initially 4 mg twice daily for 4 weeks, increased to 8 mg twice daily for at least 4 weeks; maintenance 8–12 mg twice daily Modified-release capsule: Initially 8 mg once daily for 4 weeks, increased to 16 mg once daily for at least 4 weeks; maintenance 16–24 mg daily. Available as: tablet, modified-release capsule, oral solution	Initially 5 mg once daily, then increased in steps of 5 mg every week; usual maintenance 20 mg daily; maximum 20 mg per day (Should be taken at the same time every day) Available as: tablet, orodispersible tablet, oral solution.
Reducing or stopping	Reduce from 10 mg to 5mg for one month and monitor, or stop Discontinuation should be considered when evidence of a therapeutic effect is no longer present. Individual response to donepezil cannot be predicted. Upon discontinuation of treatment, a gradual abatement of the beneficial effects of donepezil is seen.	Reduce by 3 mgs every two weeks or reduce patch to 4.6 mgs for a month and monitor, or stop If after 3 months of maintenance dose treatment the patient’s rate of decline in dementia symptoms is not altered favourably, the treatment should be discontinued. Discontinuation should also be considered when evidence of a therapeutic effect is no longer present.	Reduce by 4 mgs every 2 weeks and monitor, or stop Discontinuation of galantamine should be considered when evidence of a therapeutic effect is no longer present or if the patient does not tolerate treatment.	Reduce by 5 mgs every 2 weeks or 10 mgs monthly, and monitor, or stop Discontinuation of memantine should be considered when evidence of a therapeutic effect is no longer present or if the patient does not tolerate treatment.

Donepezil, Rivastigmine and Galantamine

Memantine

Adverse Effects

See individual SmPCs at Home – electronic medicines compendium (emc)

The most common adverse effects include diarrhoea, nausea, vomiting, muscle cramps, dyspepsia, fatigue, insomnia, anorexia, weight loss, dizziness, headache, and somnolence.

Other side-effects include confusion, fall, injury, syncope, upper respiratory tract infection and urinary tract infection.

Some patients complain of irritability and aggression as side-effects.

The most common adverse effects include constipation, hypertension, dyspnoea, headache, dizziness, drowsiness

Other side-effects include vomiting, thrombosis, heart failure, confusion, fatigue, hallucinations, and abnormal gait and very rarely seizures, pancreatitis, psychosis, depression, and suicidal ideation.

Drug Interactions	Interactions A to Z \| BNF \| NICE
Cautions	See individual SmPCs at Home – electronic medicines compendium (emc)
Contraindications	See individual SmPCs at Home – electronic medicines compendium (emc)

Monitoring

See Medicines Monitoring – SPS – Specialist Pharmacy Service – The first stop for professional medicines advice

BASELINE MONITORING

o Donepezil, rivastigmine, galantamine and memantine –
·   Pulse should be monitored at each review or more frequently if symptomatic/the patient has risk factors for bradycardia.
·   Weight is recommended followed by 6-12 monthly review (weight loss can occur).
·    Liver function tests
·    Renal function- estimated glomerular filtration rate

o Memantine –
– Reduce dose to 10 mg daily if eGFR 30–49 mL/minute/1.73 m², if well tolerated after at least 7 days dose can be increased in steps to 20 mg daily.
– Reduce dose to 10 mg daily if eGFR 5–29 mL/minute/1.73 m²

o Galantamine –
– For patients with a creatinine clearance ≥9 ml/min, no dosage adjustment needed.
– Serum potassium – for galantamine only.

ONGOING MONITORING

·   Pulse should be monitored at each review or more frequently if symptomatic/the patient has risk factors for bradycardia.
·   Weight is recommended followed by 6-12 monthly review (weight loss can occur).
·   Renal function

Serum potassium for galantamine only

Be aware that the evidence does not support adding memantine to an AChE inhibitor in moderate to severe disease – there is no real additional benefit.

NICE suggests, for people with an established diagnosis of Alzheimer’s disease who are already taking an AChE inhibitor:

consider memantine in addition to an AChE if they have moderate disease
offer memantine in addition to an AChE if they have severe disease

If prescribing an AChE inhibitor (donepezil, galantamine or rivastigmine), treatment should normally be started with the drug with the lowest acquisition cost (taking into account required daily dose and the price per dose once shared care has started). However, an alternative AChE inhibitor could be prescribed if it is considered appropriate when taking into account adverse event profile, expectations about adherence, medical comorbidity, possibility of drug interactions and dosing profiles.

If someone has stopped medication and thinks they should restart again they should talk to their doctor as soon as possible.
It is recommended good practice to exclude delirium/depression, and baseline investigations such as MSU, ECG, and blood tests (FBC, U&E’s, LFT’s, glucose, TFT’s, B12, folate and calcium) and physical examination if dementia is suspected.
Review patients’ use of medicines associated with increased anticholinergic burden (ACB), and if possible, look for alternatives. Include over the counter medications in the assessment. The presence of a substantial ACB may mimic the symptoms of dementia and therefore lead to a false diagnosis of dementia.
Long-term heavy alcohol consumption can result in a lack of thiamine and Korsakoff’s Syndrome – review patient alcohol intake and consider prescribing thiamine in accordance with RMOC as appropriate.
Contact the Old Age Psychiatry Service for advice and support if there are any clinical changes or concerns requiring specialist input or review.

Special Warnings and Precautions for Use

See individual SmPCs at https://www.rpharms.com/development/trainee-pharmacists/product-characteristics-summary

Several systematic reviews show that the side effects of AChE inhibitors get worse as patients gets older and frailer, and the clinical benefits which are 1 point on the Mini-mental state examination (MMSE) at 6 months in Alzheimer’s disease, are quickly outweighed by these side-effects. Caution should be taken with regards to prescribing for frail patients over 80 years.

What is Covered in an Annual Review?

Contact details: check that the contact details of the person’s carer, family or friends are up to date. Consider a carer’s assessment if needed.

Understanding the diagnosis: check that the person with dementia understands their diagnosis. They may confirm which type of dementia they have, for example Alzheimer’s disease, vascular dementia, or another type, and what this means.

Welfare questions: To make sure everyone is safe and well, check whether the person with dementia or their carer is at risk of harm, or of not looking after themselves properly. You may ask whether there is anything causing them to feel stressed or uncomfortable. You might also ask about the person’s hobbies, interests or how they are managing daily activities. They may ask what living well means to the person with dementia, and what support they need to continue to live well.

Medication review: Part of the annual review is talking about any medication the person is taking for dementia or any other conditions they have (for example, high blood pressure). Please check they are not taking any unnecessary medication. Check if there still be any benefit of the medications use.

If they recommend new medication, it can help to ask:

what each drug is for and how it should help
how and when it should be taken
whether there are any side effects to watch out for.

Consider advising to stop the medications:

If there is no benefit (cognitive or functional)
If the dementia progressed since last review
If no effect on BPSD
If they have side-effects or contraindications
If it is impacting their physical health or interfering with other medications.

Changes in behaviour, and mood: Ask if there are any new symptoms since the last review, and how these are affecting the person and those supporting them. You may suggest treatment, or, if the symptom cannot be treated, they may discuss ways to manage it.

Experiencing changes: As dementia progresses, the person with dementia will experience changes and this might include behaving differently. This might cause them or their carer discomfort or challenges – for example, if they are agitated or restless. The person may be distressed or indicating a need they cannot communicate or may not even be aware of when they behave in this way. The GP should be able to rule out any physical causes, such as pain or an infection, that could be contributing to the behaviour.
Support for changes in behaviour: They may also offer information and support about their behaviour or refer them on to the OPCMHT/ MAS service/ Social services/Occupational therapists.

Changes in Global Functioning: Please ask about activities of daily living skills (ADL).

Basics ADLs (skills needed to take care of personal needs):

Instrumental ADLs (skills needed to function within the community and society)

Advance care planning: Please consider starting or revisiting discussions about advance care planning. They may describe what could happen in the future if the person no longer has capacity to make decisions about treatment and care – and particularly the following options.

Lasting power of attorney (LPA) for England and Wales that allow a person to appoint another person to make medical or financial decisions for them, for when they are no longer able to make those decisions themselves in the future.
Will writing
Advance decisions for England and Wales that allows a person with capacity to refuse, in advance, specific medical procedures or treatments. Like LPAs, advance decisions are legally binding. This means that health professionals must follow these decisions if they can.
Advance statements: These allow a person to explain what they like and do not like, and to set out their preferences for the future. Unlike LPAs and advance directives, advance statements are not legally binding, but they must still be considered.
End of life care: Thinking about care and end of life care can be distressing. It can also be reassuring to know that the person has done what they can to record their decisions and preferences in advance of the time when any decisions need to be made. It can allow them to then focus on living well.

Support for carers review: Review the carers own needs and available support. Please consider carer assessment.

Making the Decision to Stop Dementia Medication

Medication should be reviewed regularly and continued for as long as the benefits outweigh any side effects.

A decision to stop medication should be made after consultation with family and carers who know the person well.

Do not stop AChE inhibitors in people with Alzheimer’s disease because of disease severity alone.

The treatment may be stopped if:

The person becomes unable to take the medicines in the way prescribed, even with support from someone else.

The desired effects (stabilising cognitive and functional status) are not perceived within a reasonable time (e.g., 12 weeks). In some cases, stopping AChE inhibitor therapy may cause negative effects on cognition and neuropsychiatric symptoms.

A patient has an apparently negative reaction to the medication.

A patient’s cognitive and functional decline has continued to the degree that they need full time care and/or full assistance with their activities of daily living (i.e., washing, feeding, toileting etc.)

For patients fitting the above criteria, medication can be stopped by primary care. If there are concerns, consider liaising/ discussing with the old age psychiatric team.

Maintenance of treatment can be continued as long as therapeutic benefit is observed. Response cannot be predicted so regular reviews should be undertaken to establish benefit of therapy.

If someone has stopped medication and thinks they should restart again they should talk to their doctor as soon as possible.

Shared Care Protocol

References