Pharmacological management of Alzheimer's disease

(From NICE NG97, June 2018)

The three acetylcholinesterase (AChE) inhibitors donepezil, galantamine and rivastigmine as monotherapies are recommended as options for managing mild to moderate Alzheimer's.

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. Ongoing use in severe disease is off-label, however stopping would be as per guidance below.

Treatment should be under the following conditions:

• For people who are not taking an AChE inhibitor or memantine, prescribers should only start treatment with these on the advice of a clinician who has the necessary knowledge and skills. This could include:
  • secondary care medical specialists: psychiatrists, geriatricians and neurologists
  • other healthcare professionals (GPs, nurse consultants and advanced nurse practitioners), if they have specialist expertise in diagnosing and treating Alzheimer's disease.
• Once a decision has been made to start an AChE inhibitor or memantine, the first prescription may be made in primary care.
• 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.
• Do not stop AChE inhibitors in people with Alzheimer's disease because of disease severity alone (other issues will determine discontinuation, such as worthwhile maintenance of cognitive, global, functional or behavioural symptoms, concurrent physical illness with contraindications, side-effects or clearly at palliative stage of care).
• Do not offer statins, aspirin, hypertension medication or diabetes medication to treat vascular dementia. There is a lack of evidence for this. Use these treatments in line with their usual respective guidelines.

Additional notes

• If starting medication for dementia, review other medications to ensure there are no drugs worsening cognition e.g. anticholinergics.
• Pharmacological therapy is based on modest clinical impact from studies mostly over 3-6m on symptom progression and possible increasing time to institutionalisation. With minor adverse symptoms fairly common, starting low and going slow is important.
• NG97 also covers the pharmacological management of non-Alzheimer’s dementia and in particular the use of AChE inhibitors and memantine in Lewy Body Dementia and mixed dementia.
• Cholinesterase inhibitors and memantine can be used to treat behavioural and psychological symptoms of dementia in some cases, meaning that they should not be discontinued for these individuals even if there is evidence of ongoing cognitive decline.

Every person in Scotland with a new diagnosis of dementia is entitled to a minimum of 12 months of post diagnostic support, delivered by a named individual who will work closely with them and their family/carers. The support is delivered through the Alzheimer’s Scotland 5 Pillars Model and covers five broad areas;

• Understanding the illness and managing symptoms
• Planning for future decision-making
• Supporting community connections
• Peer support
• Planning for future care
• Further information can be found on the Alzheimer’s Scotland website.

Referrals for PDS can be made to the following addresses;

• Angus Post Diagnostic Dementia Service, Susan Carnegie Centre, Stracathro Hospital Brechin DD9 7QA.
• Dundee Post Diagnostic Dementia Service, Kingsway Care Centre, Kings Cross Road, Dundee DD2 3PT.
• Perth and Kinross Post Diagnostic Dementia Service is incorporated into the CMHTs and referrals can be made in writing or by email;

North West - tay.nwpopcmht@nhs.scot
Strathmore - tay.strathmoreopcmht@nhs.scot
South - tay.southperthshireopcmht@nhs.scot
Perth City - tay.pcopcmht@nhs.scot

Once the patient has been discharged to Primary Care, typically after 12 months, any concerns or requests for advice can be directed to POA services through the Referral Management System under “For Advice”.

If the GP has urgent concerns then an urgent referral can be made through the electronic referral system or over the telephone to the Older People’s Community Mental Health Team duty worker in each area.

Dundee: duty worker in specific locality

• CMHT West 01382 647299
• CMHT East 01382 647298

Angus: duty worker in specific locality

• South 01241 465227
• North East 01356 237111
• North West 01307 475288

Perth and Kinross: duty worker in specific locality

• North West 01796 474818
• Strathmore 01250 877843
• South 01764 653173
• Perth City 01738 562231

Out of Hours: Crisis Team at Carseview 01382 423053.

Stages of Alzheimer's Type Dementia (Alzheimer's Association)

Severity of the illness cannot be determined by just cognitive performance; therefore the information gathered from relatives/carers is required to establish the stages of the illness.

Moderate Alzheimer's disease (middle stage)

Moderate Alzheimer's is typically the longest stage and can last for many years. As the disease progresses, the person with Alzheimer's will require a greater level of care.

During the moderate stage of Alzheimer’s, the dementia symptoms are more pronounced. A person may have greater difficulty performing tasks, such as paying bills, but they may still remember significant details about their life.

You may notice the person with Alzheimer's confusing words, getting frustrated or angry, or acting in unexpected ways, such as refusing to bathe. Damage to nerve cells in the brain can make it difficult to express thoughts and perform routine tasks.

At this point, symptoms will be noticeable to others and may include:

• Forgetfulness of events or about one's own personal history
• Feeling moody or withdrawn, especially in socially or mentally challenging situations
• Being unable to recall their own address or telephone number or the high school or college from which they graduated
• Confusion about where they are or what day it is
• The need for help choosing proper clothing for the season or the occasion
• Trouble controlling bladder and bowels in some individuals
• Changes in sleep patterns; sleeping during the day and becoming restless at night
• An increased risk of wandering and becoming lost
• Personality and behavioural changes, including suspiciousness and delusions or compulsive, repetitive behaviour like hand-wringing or tissue shredding.

Severe Alzheimer's disease (late stage)

In the final stage of this disease, dementia symptoms are severe. Individuals lose the ability to respond to their environment, to carry on a conversation and, eventually, to control movement. They may still say words or phrases, but communicating pain becomes difficult. As memory and cognitive skills continue to worsen, significant personality changes may take place and individuals need extensive help with daily activities.

At this stage, individuals may:

• Need round-the-clock assistance with daily activities and personal care
• Lose awareness of recent experiences as well as of their surroundings
• Experience changes in physical abilities, including the ability to walk, sit and, eventually, swallow
• Have increasing difficulty communicating
• Become vulnerable to infections, especially pneumonia
• Behavioural disturbance at the severe stage may simply be a manifestation of pain. 63% of patients will improve with paracetamol alone¹.

Psychotic symptoms are common (up to 18% of patients with dementia).

Ensure non-medical approaches have been used in the first instance including checking for pain, psychosocial and environmental changes and personalisation of activities to improve engagement/pleasure/interest.

Consider offering antipsychotics to patients if risking self/others or experiencing agitation/hallucinations/delusions which are distressing and discuss with patient/family/carers.

There is a lack of evidence for the efficacy of antipsychotics to treat agitation and aggression in dementia. Consider and treat underlying causes such as pain, constipation and delirium.

Remember that visual hallucinations are a core feature of Lewy Body Dementia and people with this condition commonly develop other psychotic symptoms but antipsychotics should be avoided in this patient population given the significant risk of adverse events including a 2 to 3 fold increase in mortality. Cholinesterase inhibitors are often helpful for visual hallucinations in this group.

Consider whether there is evidence of low mood or anxiety, in which case an antidepressant may be beneficial instead.

Use at the lowest dose possible initially for up to 6 weeks. Only risperidone and haloperidol are licensed. Reassess at 6 weeks and stop if no ongoing benefit. Adverse effects² include: a 1% increase in mortality at 12 weeks of use. By 3 years of use those who have stopped have 30% lower mortality (strokes are up to 3x as common (meta-analysis of those on risperidone) and they can increase extra-pyramidal SEs.

Please refer to the Tayside Area Formulary for more information.

1. Husebo B S, Ballard C, Sandvik R, Nilsen O B, Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial BMJ 2011; 343 :d4065 doi:10.1136/bmj.d4065.

2. Corbett A, Burns A, Ballard C. Don’t use antipsychotics routinely to treat agitation and aggression in people with dementia BMJ 2014; 349 :g6420 doi:10.1136/bmj.g6420.