Essential facts on the diagnosis and management of Alzheimer.pdf

8/16/2019 Essential facts on the diagnosis and management of Alzheimer.pdf

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This module provides the essential facts on the

diagnosis and management of Alzheimer's

disease in primary care.This module provides the essential facts on the diagnosis and management of Alzheimer's disease in

primary care. It is based on the best available evidence. After reading the module, you can test your

knowledge with our "best of many questions" quiz.

About the author

Elizabeth England is a general practitioner in Birmingham and a Clinical Research Fellow in the

Department of Primary Care and General Practice at Birmingham University. Her specialist interest

is mental health.

Why I wrote this module

"Patients with Alzheimer's disease will often present to your general practice, but the national

service framework for older people says that diagnosis may be difficult.1

"I wanted to write this module to help you diagnose and assess Alzheimer's disease. I now feel more

confident about making the diagnosis and deciding which patients to refer early for specialist care.

“There is still a lack of clarity regarding treatments for Alzheimer’s disease and I wanted to ensure I

was up to date with the best evidence available.

"As part of my personal development plan, I was interested in learning about the role that carers

play in managing this disease and how I could better support them. I learnt where to send carers for

further help."

Key points

Memory problems in people aged


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No evidence is available on long term treatment

Clinical tips

Suspect dementia when a patient's family is concerned about deterioration in activities of

daily living (for example, managing money)

Some people with dementia may score higher than 26-30 on the mini mental state

examination. This is especially true of people who had a high baseline verbal fluency and

spent more than 10 years in education

Quality of life is more important than cognitive function to most patients and their carers

(but most studies have measured outcomes such as cognitive function)

What is Alzheimer's disease?

People with Alzheimer's disease experience global, progressive impairment of brain function. Thisimpairment is irreversible and leads to reduced intellectual ability.3 Alzheimer's disease has a

chronic, insidious onset. It can be difficult to distinguish the earliest signs of Alzheimer's disease

from those of normal ageing.4

Who gets it?

In total, 70% of patients with dementia have Alzheimer's disease.5

Each year, the average general practitioner will6:

See two patients with new onset dementia

Have seven consultations with patients related to their diagnosis of dementia.

Risk factors for Alzheimer's disease include3 7:

Age (Alzheimer's disease affects 20% of people aged >80 years)

White ethnicity

Female sex

Family history (having a first degree relative with Alzheimer's disease).

How do I diagnose it?

Alzheimer's disease is diagnosed on the basis of history, examination, cognitive testing, and

investigations. It is accurately diagnosed in about 70% of cases.

History

Alzheimer's disease typically presents with memory impairment.

Relatives, however, often complain of a variety of problems3 5:

"He keeps losing his money"


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"He's not the man he used to be"

"He loses his temper over the smallest thing"

"He thinks we are all plotting against him"

"He has given up"

"He won't eat"

"He gets lost in his own street""He gets much worse at night."

Examination

Most patients with Alzheimer's disease have a normal physical examination. Late signs include

ataxic gait and myoclonus.

Physical examination can help exclude delirium or other causes of dementia. Signs of delirium

include fever, dehydration, tachycardia, dyspnoea, reduced or fluctuating levels of consciousness,

and agitation.

Cognitive testing in Alzheimer's disease

Mini mental state examination

The mini mental state examination is a 30 point test of various cognitive domains (for example,memory and language function).

The patient's verbal fluency, age, education, and social group can all influence the test score.

Scores of >26 make a diagnosis of dementia unlikely

Scores of 21-26 may indicate mild dementia

Scores of 10-20 may indicate moderate dementia

Scores of


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Attention and calculation

Subtract seven from 100.

Stop after five answers. ( 93, 86, 79, 72, 65)

Alternatively

Spell the word "world" backwards. ( d, l, r, o, w)

5

Recall

What were the three words I asked you to say earlier?

(Skip this test if all three objects were not remembered during

registration test)

3

Naming

Name these objects. (show a watch and a pencil)

2

Repeating

Repeat the following: "no ifs and/or buts"

1

Reading

Write "Close your eyes" on a card.

Read this sentence and do what it says

1

Writing

Can you write a short sentence for me?

1

Language: three stage command

Take this piece of paper in your left hand, fold it in half, and put it on

the floor

3

Construction

Copy this drawing please

1

Total score (out of 30)

Clock drawing test

Another screening test is the clock drawing test. The patient is asked to draw a clock and then write

in the numbers 1-12.

An inability to complete the test has a diagnostic sensitivity of 87% and specificity of 93% for

Alzheimer's disease.9


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If the patient's ability to draw the hands of the clock at 11.20 is included, the sensitivity and

specificity are increased further.

Investigations

No diagnostic test exists for Alzheimer's disease.

Tests are used to rule out other causes of dementia or diagnose delirium, but little evidence shows

which tests should be done.10

Laboratory tests

You should check vitamin B12 levels and do thyroid function tests.11

No clear evidence supports or refutes any other "routine" blood or urine tests.11

The choice of other tests (including tests for neurosyphilis) should be tailored to the individual

patient.

Brain imaging

Guidelines on dementia recommend structural imaging to exclude other underlying causes of

confusion and memory impairment preferably by MRI although CT is an alternative option.12

Perfusion hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed

tomography (SPECT) should be used to help differentiate Alzheimer’s disease, vascular dementia,

and frontotemporal dementia if the diagnosis is in doubt. These are not diagnostic tests though and

availability of scanners is limited.10

Genetic testing

Genetic testing for Alzheimer's disease is controversial. The apolipoprotein E4 allele has been

linked to the disease, but genetic testing currently is not recommended.13

No definitive diagnostic investigation exists except post-mortem examination.14

Other causes of dementia

Alzheimer's disease should be diagnosed only after other psychiatric, neurological, or vascular

causes of confusion are excluded.

Vascular dementia

This accounts for about 20% of patients with dementia. Although it can result from a single stroke,

the most common cause is multiple small infarcts that may have gone undetected (multi-infarct

dementia).

Multi-infarct dementia should be considered in patients with a history of:

Hypertension

Diabetes


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Stroke

Transient ischaemic attack

Cigarette smoking.

Multi-infarct dementia is characterised by patchy cognitive deficits and a stepwise progression. It

may occur concomitantly with Alzheimer's disease.15

It is important to diagnose vascular dementia, as treatment with aspirin and control of other risk

factors may slow the progression of decline.

Lewy body dementia

This accounts for up to 20% of patients with dementia.

The diagnosis of Lewy body dementia is challenging.16

It is characterised by progressive cognitive decline along with two of the following:

Fluctuating cognition

Visual hallucinations

Spontaneous motor features of parkinsonism.

It is important to diagnose Lewy body dementia as patients with this condition develop severe

parkinsonism when given neuroleptics.

Less common causes of dementia

Less common causes of dementia include15:

Severe depression, which can masquerade as, and is a risk factor for, dementia

Parkinson's disease

Huntington's disease

Multiple sclerosis

Creutzfeldt-Jakob disease

Head trauma

Hypothyroidism

Neurosyphilis

Normal pressure hydrocephalus

AIDS (AIDS-dementia complex).

How to distinguish depression from dementia17 18

Severe depression can mimic dementia in the elderly.

In depression:

The onset is usually more rapid (Alzheimer's disease is insidious)

The patient may have a past history of depressionPatients complain of waking early in the morning, poor appetite, apathy, poor concentration,

irritability, low self esteem, guilt, or suicidal ideation


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Patients may have impairment of long term memory and short term memory in contrast with

the short term memory impairment seen in patients with dementia

Cognitive function and symptoms may be variable.

If you have any doubt about the diagnosis, referral to secondary care is appropriate.2

How do I treat it?

Recent advances have been made in the treatment of Alzheimer's disease, but the actual treatment

related improvements in cognitive function have been small. As a result, to improve the lives of

patients with Alzheimer's disease remains challenging. Managing memory loss and managing

behavioural problems are equally important.

Managing memory loss

Non drug treatments

Cognitive rehabilitation and training

Reality orientation, which forms part of cognitive rehabilitation and training, involves continually

presenting information to patients with dementia to keep them oriented in person, time, and place. It

can include posting up to date information on the day, date, and season on a convenient board.

Nursing home staff can reorient patients at times of contact.

The premise that underlies reality orientation is that helping to orient patients with dementia will

provide them with a better understanding of their surroundings. This could have the effect ofimproving their sense of self esteem and control.

Benefits

Reality orientation improves the memory and behaviour of elderly patients with dementia.

Side effects

No evidence of any harms exists.

Evidence

A single systematic review of six trials concluded that cognitive rehabilitation and cognitive

training can produce a moderate, non-significant effect on cognitive function. Neither studies nor

outcomes were standardised in these studies.20

Drug treatments

Patients with Alzheimer's disease are often reluctant to take tablets. It is important to explain to the

patient and carer what the tablets are for and the possible side effects.

4


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Cholinesterase inhibitors

Randomised controlled trials have found that cholinesterase inhibitors produce small improvements

in cognitive and global assessments in people with mild to moderate dementia.4 Currently only the

three acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine are recommended as

options in the management of people with Alzheimer’s disease of moderate severity only (MiniMental State Examination score of between 10 and 20 points), and under certain conditions which

include assessment and follow up in secondary care under a specialist.10 21

Donepezil

Benefits

Donepezil improves cognitive function in patients with Alzheimer's disease. It is well tolerated, but

its effects on quality of life are not clear.22

Side effects

All cholinesterase inhibitors have these side effects:

Abdominal pain

Diarrhoea

Nausea

Vomiting.

Patients have also described:

Agitation

Headache

Insomnia.

Evidence

A systematic review assessed 24 trials involving 5796 participants with mild to moderate

Alzheimer's disease over a range of time varying from 12-52 weeks of treatment. Individuals with

mild, moderate, or severe dementia due to Alzheimer's disease treated for periods of 12-52 weeks

with donepezil experienced benefits in cognitive function, activities of daily living, and behaviour.

Effects on cognition remained measurable and statistically significant at 52 weeks of treatment in

one study.22 There is some evidence that use of donepezil is neither more nor less expensive

compared with placebo when assessing total healthcare resource costs. The debate on whether

donepezil is effective continues despite the evidence of efficacy from the clinical studies because

the benefits of donepezil are small when compared to the actual cost of the drug.22

Trials of cholinesterase inhibitors in patients with Alzheimer's disease have used proxy outcomes

(such as cognitive scores) rather than outcomes more likely to mean something to patients and

caregivers. Patients enrolled in trials of donepezil were highly selected and may not have been

representative of all patients with Alzheimer's disease.23

Dosing


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Donepezil is taken once daily (5-10 mg). This may give donepezil an advantage over othercholinesterase inhibitors, which must be taken twice daily. A response is generally seen 2-4 months

after treatment is started.

Galantamine

Benefits

Galantamine improves cognitive, functional, and behavioural symptoms in patients with

Alzheimer's disease. Improvements last for six months or more.

Side effects

Adverse effects include:

Nausea (in 44% of patients)Vomiting (in 20% of patients)

Dizziness.

Up to 40% of patients stop treatment because of side effects.24

Evidence

A systematic review of 10 trials involving 6805 subjects with mainly mild to moderate dementia

over varying periods from 3-6 months found that galantamine improved cognitive function and

overall clinical status when compared to placebo. However galantamine is not recommended in

mild cognitive impairment, as there was an excess of unexplained deaths in two trials exploring theuse of galantamine in this group.25

Dosing

Initially 4 mg twice daily for four weeks; this is increased to 8 mg twice daily for four weeks.

Maintenance involves 8-12 mg twice daily. A 16 mg slow release preparation is also available.

Rivastigmine

Benefits

Rivastigmine gives small but significant improvements in patients with mild to moderate

Alzheimer's disease.26

Side effects

Side effects include nausea, vomiting, diarrhoea, abdominal pain, dizziness, headache, and loss of

appetite.

Side effects are seen in up to 35% of patients.

Evidence


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A systematic review of seven trials involving 3450 participants assessing rivastigmine concludedthat 6-12 mg rivastigmine produced cognitive improvement when compared to placebo. Smaller

doses were ineffective.26

All trials of cholinesterase inhibitors in Alzheimer's disease have used proxy outcomes, such as

cognitive scores, rather than outcomes more likely to mean something to patients and those whocare for them. Rivastigmine is the only cholinesterase inhibitor to be studied in a routine clinical

setting.26

Dosing

Dose is initially 1.5 mg twice daily, which is increased in steps of 1.5 mg twice daily at intervals of

at least two weeks according to response and tolerance. The usual dose range is 3-6 mg twice daily,

with a maximum dose of 6 mg twice daily.

Donepezil, galantamine, and rivastigmine

Evidence

A recent Cochrane review demonstrated that all three cholinesterase inhibitors are effective for

patients with mild to moderate Alzheimer's disease generally - with improvements seen over a six

month period in improving cognitive function, activities of daily living, and behaviour - although

none of these effects are large. A plateau then appears to be reached. There was no difference in

efficacy between the three drugs. The evidence from one large trial suggests that donepezil has less

side effects compared to rivastigmine. In general the benefits of these drugs in mild Alzheimer's

disease are small and sometimes not clinically apparent giving rise to the debate as to the cost

effectiveness of these drugs.

A further systematic review undertaken also failed to support the use of cholinesterase inhibitors for

patients with Alzheimer's disease. This review concluded that although a large number of

randomised controlled trials demonstrated positive benefits when compared to placebo, the effects

were modest on rating scales and the methodological quality of many of the trials was poor.27

Ginkgo biloba

Ginkgo biloba is an extract of leaves from the maidenhair tree, which is indigenous to China and

cultivated throughout the world. It has been used as a herbal remedy for many conditions.28

Benefits

Ginkgo biloba may improve cognition in patients with Alzheimer's disease.

Side effects

Side effects are extremely infrequent in studies. The most common problems were:

Gastrointestinal discomfort

HeadacheDizziness.


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Because of Ginkgo biloba's inhibitory effect on platelet activating factor, it may enhance bleeding

in patients who are taking anticoagulant and antithrombotic drugs. In addition, some experts instruct

patients to discontinue Ginkgo biloba 36 hours before surgery to reduce the risk of bleeding

complications.26

People who use aspirin or warfarin chronically may get spontaneous bleeding if they take Ginkgobiloba. Interactions with monoamine oxidase inhibitors and papaverine also are possible.

Evidence

A systematic review showed promising evidence of improvement in cognition and function

associated with Ginkgo biloba. Three of the more modern trials in the review, however, showed

inconsistent results.29

Dosing

The usual dose is 120-240 mg daily as two to three doses a day. Patients should be reviewed every

three months to six months to assess response.

Vitamin E

Vitamin E (Alpha tocopherol) is an anti-oxidant. It is a lipid soluble vitamin that interacts with cell

membranes to trap free radicals and interrupt cell damage.

Benefits

Although earlier trials suggested benefits, more recent studies have not demonstrated any effect oncognitive function in patients with Alzheimer's disease taking Vitamin E.

Side effects

Vitamin E may cause diarrhoea and abdominal pain when taken in higher doses. There was an

excess of falls in patients receiving vitamin E.

Evidence

One randomised clinical trial found no benefit on cognition for patients with Alzheimer's disease but patients were less likely to reach one of four endpoints including death and institutionalisation.30

A recent randomised controlled trial demonstrated that Vitamin E had no effect on 769 patients with

mild cognitive impairment.31

Statins

Statins may retard or prevent the pathogenesis and clinical expression of Alzheimer's disease.

Benefits

There is a growing body of epidemiological, biological, and limited evidence from non-randomisedtrials to support the theory that lowering cholesterol levels may retard or stop the pathogenesis of

Alzheimer's disease.


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Side effects

Statins may cause muscle pains (rarely rhabdomyolysis) and derangement of liver function.

Evidence

Initial epidemiological and clinical trials data about whether statin use reduces the risk of

Alzheimer's disease suggested that statins might prevent dementia. Next, two large clinical trials

with cognitive add-on studies showed no benefit and neither did a further group of observational

studies. The latter were mostly longitudinal, and were criticised on methodological grounds. Most

recently, the Canadian Study of Health and Aging has produced a mixed result. Initial reports may

have overestimated the extent of protection of statins, suggesting a more modest role for the use of

statins in the primary prevention of Alzheimer's disease.32

Behavioural problems

Behavioural problems including aggression and agitation, and sometimes disinhibition can be a

feature of Alzheimer's disease.4 20

You should exclude treatable causes (for example, physical illness and environmental

discomfort)

Behavioural problems can be the most stressful part of the illness for the carer

You should offer carers education and support, although these do little to relieve the burden.

Non-pharmacological measures

Experts suggest the following measures33 34:

Maintain a routine (for example, regular mealtimes and activities)

Ensure autonomy (for example, the patient should have their own clothes and privacy)

Simplify tasks into steps

Offer assistive technology (eg community alarm service, able to respond in an emergency

and provide regular contact by telephone, detectors or monitors such as motion or falls and

fire and gas that trigger a warning to a response centre)35 36

Provide a safe environment (for example, with furniture and rugs)

Use night lights in bedrooms to reduce confusion at night

Minimise excess stimulation (for example, crowds and television)Ensure comorbid conditions are treated (for example, check vision and hearing, and

rationalise drugs)

Offer carers strategies and advice to minimise and anticipate challenging behaviour

Ensure health and social care professionals caring for patients are appropriately trained to

anticipate behaviour that challenges and how to manage violence, aggression, and extreme

agitation, including de-escalation techniques and methods of physical restraint10

In residential accommodation ensure adequate staff training, attention, and clinical

leadership.


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Cognitive training and rehabilitation

This involves continually presenting information to patients with dementia to keep them oriented in

person, time, and place. It can include posting up to date information on the day, date, and season

on a convenient board. Nursing home staff can reorient patients at times of contact as needed.

Benefits

Reality orientation improves memory and behaviour of elderly patients with dementia.

Side effects

No evidence of any harm exists.

Evidence

A single systematic review of six randomised controlled trials concluded that reality orientation

improved behavioural symptoms. Neither interventions nor outcomes, however, were standardised

in these studies.2

Aromatherapy

Aromatherapy is reported to be the most widely used complementary therapy in the British National

Health System and has been used in people with dementia to reduce distressed behaviour, promote

sleep, and stimulate motivational behaviour.

Benefits

Aromatherapy may have a beneficial effect on agitation and neuropsychiatric symptoms.

Side effects

There is no particular evidence of harm caused by aromatherapy.

Evidence

Only one trial was of sufficient quality to be included in a systematic review and although itdemonstrated a positive effect on behaviour and neuropsychiatric symptoms in people with

dementia, it was methodologically poor.37

Drug treatments

Atypical and typical anti-psychotics

Atypical antipsychotics include olanzapine, risperidone, and quetiapine for example. Haloperidol is

a typical antipsychotic. Evidence is accumulating regarding the risks of prescribing antipsychotics

for patients with Alzheimer’s. A recent study published in the Lancet has shown that antipsychoticsincrease one year mortality by 42% which is important in view of the increasing long term survival


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seen in Alzheimer’s patients. They recommend the use of antidepressant citalopram, psychological

therapy, or memantine as alternatives.38

The National Institute for Health and Clinical Excellence (NICE) already recommends that the

drugs should only be considered in people with dementia if they have severe psychiatric symptoms,

and that they should be used for a limited period only; should only be prescribed after a full risk benefit analysis has been carried out, discussed fully with the patient's carers, and a regular review

plan put in place.

Patients with mild, moderate, or severe Alzheimer’s disease with disturbing cognitive features or

challenging behaviour causing distress to the patient or potential harm who have not responded to

non-drug treatment or antipsychotic medication or where it is inappropriate may be offered an anti-

cholinesterase inhibitor.10

Benefits

Initial studies suggested that antipsychotics have modest efficacy in improving neuropsychiatricsymptoms in Alzheimer's disease.39

Side effects

But they can have many side effects including:

Accelerated cognitive decline

Increased risk of stroke

Tardive dyskinesia

Cardiac arrhythmias.

Evidence

In a recent review, four trials looking at typical antipsychotics (two meta-analyses and two RCTs)

were examined. Generally, no difference among specific agents was found and efficacy was small

at best, and adverse effects were common. Six RCTs with atypical antipsychotics were reviewed.

Results showed modest, statistically significant efficacy of olanzapine and risperidone, with

minimal adverse effects at lower doses.40

Mood stabilisers

Carbamazepine

Benefits

Carbamazepine is an antiepileptic drug that can reduce agitation and aggression in patients with

dementia.

Side effects

Side effects include tics, ataxia, and a risk of cardiotoxicity.41

Evidence


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One randomised controlled trial of 51 patients showed that carbamazepine improves agitation,aggression, and global clinical status in patients with dementia.42 The majority of trials looking at

the use of drugs in behaviourally disturbed patients with Alzheimer's disease have been short term

and small scale studies limiting the usefulness of the findings.43

Dosing

Dosing begins at 100 mg/day. It can be increased by 50 mg every 2-4 days as tolerated.

Treating depression

Selective serotonin reuptake inhibitors are the preferred treatment. They are usually well tolerated,

although some patients experience sleep problems and nausea.44

Tricyclic antidepressants can accelerate cognitive loss due to their anticholinergic effects.45

Caregivers

The risk of a patient being institutionalised increases in proportion to the carer's level of stress. This

is affected by several factors, including the patient's behaviour, nocturnal wandering, and

incontinence.33

You should also be aware of the emotional difficulties associated with caring for a patient with

Alzheimer's disease.

Consider discussing the following issues with the carer:

Feelings of guilt on the carer's part if the doctor or carer suggests the patient is admitted to a

home

Social isolation

Feelings of exclusion from decision making about the patient's care

Possible financial hardship.

The prevalence of depression in carers is high, and carers perceive their physical health as being

poorer than non-carers.46

When should I refer my patient?

Early referral is important for a number of reasons1:

To make an accurate diagnosis

To exclude reversible causes of dementia

To treat with acetylcholinesterase inhibitors

To detect and manage neuropsychiatric and behavioural complications

If there are any concerns or issues regarding adult protection such as risk or neglect10

All patients should have access to a specialist.

The national service framework also recommends the involvement of the community mental health

team for older people for coordination of care, who can help especially with more complex cases. 1


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Follow up

Review the patient at least every six months to check on the patient and carer.20

Plan for the future (for example, discuss advanced statements, advanced decisions to refuse

treatment, Lasting Power of Attorney, and Preferred Place of Care Plan).10

What's the outlook?

Average survival after diagnosis is 7-10 years,20 although this can extend up to 20 years.47 Women

survive slightly longer than men.48

What do patients and carers want to know?

Patients and their carers want to know what Alzheimer's disease is and what treatment is available.They will want to know what the future is likely to hold for them.

Further information for patients and doctors can be found at the end of this module.

National service framework

The national service framework for older people emphasises1:

The importance of being aware of the burden placed on carers

A carer based approach

Non-pharmacological treatments (if possible)

Early referral in atypical, unusual, or complex cases or for the consideration of drugs and

specialist support services.

New GP contract

Revisions to the new GP contract for the years 2007/8 have released new points for practices that

perform certain actions related to dementia.

Records

Practices can receive up to five points by achieving DEM1 (producing a register of people with adiagnosis of dementia).

Management

Practices can receive up to fifteen points by achieving DEM2 (that is, having greater than 25-60%

of patients with dementia with a review on record in the preceding fifteen months (the review

should include an assessment of physical and mental health, coordination and communication with

secondary care, a review of the carer's needs, and need for the provision of information appropriate

to the patient's stage of illness.)

49

National Institute for Health and Clinical Excellence


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The National Institute for Health and Clinical Excellence (NICE) has recently reviewed its original

guidance for the prescribing and use of cholinesterase inhibitors.21 Cholinesterase inhibitor

prescribing is still strictly governed in the updated guidance but slightly different criteria now

apply. Patients should only be prescribed cholinesterase inhibitors if 10:

Alzheimer's disease is diagnosed in a specialist clinic according to standard diagnosticcriteria:

o A patient scores 10-20 (Alzheimer's disease of moderate severity) on the mini mental

state examination

o Memantine is not recommended as a treatment option for any stage of Alzheimer's

disease unless used as part of a clinical trial

o Mini Mental State Examination remains >10.

The prescriber should make a judgment about the likelihood of compliance. The prescription must

be initiated by a specialist (neurologist, old age psychiatrist, or geriatrician). General practitioners

can only take over prescribing under a shared care protocol.

Assessment

Patients should be reassessed at two and four months after they reach the maintenance dose of drug.

Assessments should continue every six months: the drug should be continued only if the patient has

improved or not deteriorated and if the score on the mini mental state examination remains >12.

Patients need to be assessed at six months to assess the benefit of the drug. The drug should be

discontinued if side effects do not resolve, compliance is poor, or deterioration is seen at the six

month assessment.

Effectiveness of cholinesterase inhibitors

You must give the family and patient realistic expectations of treatment33

Patients who do not respond to one drug may respond to another 33

These drugs only delay the inevitable cognitive decline in patients with Alzheimer's disease,

they do not prevent it44

Although donepezil, galantamine, and rivastigmine have been shown in trials to improve

global outcome measures in patients with Alzheimer's disease, not all patients benefit and no

way yet exists to identify which patients will benefit4

A typical improvement seen from these drugs is a 1-2 point rise in the score on the minimental state examination over a period of six months; this compares with an average decline

of 5-6 points over six months in patients who do not take such drugs44

These drugs may lead to cost savings by delaying admission of patients into institutionalised

care, although no firm evidence supports this theory44

Historical footnote

What do all the following have in common? Enid Blyton, Harold Wilson, Iris Murdoch, RonaldReagan, and Margaret Rutherford. You are right - they all suffered from dementia, a disease that

affects the great and the good as well as mere mortals. Iris Murdoch's husband wrote a memoir of

his wife as she developed Alzheimer's disease which was made into a film, Iris, starring Dame Judi

Dench and Kate Winslet.


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1. A 60 year old man visits your clinic with his wife. She is very concerned because his memory is

very poor and he also tells her that he sees people in his bedroom (when there is nobody there).

On examination, there is cogwheel rigidity in all four limbs. What is the most likely diagnosis?

a. Alzheimer's disease

b.

Vascular dementia

c. Lewy body dementia2.

A 60 year old man visits your clinic with his wife. She is very concerned because his

memory is very poor and he also tells her that he sees people in his bedroom (when there is nobody

there). On examination, there is cogwheel rigidity in all four limbs. What is the most likely

diagnosis?

Your answer Correct answer

a Alzheimer's disease

b Vascular dementia

c Lewy body dementia

5. Correct answer: Lewy body dementia

a. Alzheimer's disease

Alzheimer's disease does not typically cause visual hallucinations and parkinsonism.

b. Vascular dementia

Vascular dementia does not typically cause visual hallucinations and parkinsonism.

c. Lewy body dementia

Lewy body dementia is characterised by parkinsonism, memory loss, and visual

hallucinations.

2. You are called to see an 80 year old man with Alzheimer's disease. His score on the mini

mental state examination was 15 out of 30 when last checked. His wife has become worried

about his behaviour in recent weeks. What would you advise?

a. Reality orientation

b.

Vitamin E

c. Risperidone

3. You are called to see an 80 year old man with Alzheimer's disease. His score on the mini

mental state examination was 15 out of 30 when last checked. His wife has become worried

about his behaviour in recent weeks. What would you advise?


a Reality orientation

b Vitamin E

c Risperidone

4. Correct answer: Reality orientation


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a. Reality orientation

Reality orientation improves memory and behaviour of elderly patients with

dementia.

b.

Vitamin E

Vitamin E has not been proved to be effective in treating cognitive or behavioural

symptoms in Alzheimer's disease.

c. Risperidone

The Medicines and Healthcare Products Regulatory Agency has recently stated that

you should not use olanzapine or risperidone for the behavioural symptoms of

dementia as it may increase the patient's risk of stroke.

3.

A 70 year man visits your clinic with progressive memory impairment. You diagnose himwith mild Alzheimer's disease. His wife is very concerned about the future and asks what his

likely outlook is. What is the average survival after a diagnosis of Alzheimer's disease?

a. 3-6 years

b. 7-10 years

c. 11-14 years

4. A 70 year man visits your clinic with progressive memory impairment. You diagnose him

with mild Alzheimer's disease. His wife is very concerned about the future and asks what his

likely outlook is. What is the average survival after a diagnosis of Alzheimer's disease?


a 3-6 years

b 7-10 years

c 11-14 years

6. Correct answer: 7-10 years

a. 3-6 years

Average survival after a diagnosis of Alzheimer's disease is 7-10 years.

b. 7-10 years


c. 11-14 years


4.

A 70 year old woman complains of a poor memory. She says she cannot remember anything

and answers "I don't know" to many of the questions in the mini mental state examination,

but when you press her she comes up with the right answer. She also describes poor sleep

and has lost interest in many of her previous activities. What is the most likely diagnosis?


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a.

Alzheimer's disease

b. Depression

c. Huntington's disease

5. A 70 year old woman complains of a poor memory. She says she cannot remember anything

and answers "I don't know" to many of the questions in the mini mental state examination,

but when you press her she comes up with the right answer. She also describes poor sleep

and has lost interest in many of her previous activities. What is the most likely diagnosis?


a Alzheimer's disease

b Depression

c Huntington's disease

7.

Correct answer: Depressiona. Alzheimer's disease

Poor sleep, loss of interest in previous activities, and complaints of a poor memory

strongly suggest depression. Her ability to answer the questions in the mini mental

state examination correctly makes Alzheimer's disease less likely.

b. Depression


strongly suggest depression.

c. Huntington's disease


strongly suggest depression. Huntington's disease typically causes dementia and

chorea in middle age.

Just in time


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1. An 80 year old man visits your clinic with his wife. She is concerned because his memory isvery poor. She says his memory problems came on suddenly about nine months ago and that

she's noticed a stepwise deterioration in his memory since then. He has a history of

hypertension and is taking atenolol 50 mg daily. What is the most likely diagnosis?

a. Vascular dementia

b. Alzheimer's disease

c.

Creutzfeld-Jakob disease

2. An 80 year old man visits your clinic with his wife. She is concerned because his memory is

very poor. She says his memory problems came on suddenly about nine months ago and that

she's noticed a stepwise deterioration in his memory since then. He has a history of

hypertension and is taking atenolol 50 mg daily. What is the most likely diagnosis?


a Vascular dementia

b Alzheimer's disease

c Creutzfeld-Jakob disease

3. Correct answer: Vascular dementia

a. Vascular dementia

Poor memory that comes on suddenly and gets worse in a stepwise manner suggests

vascular dementia. Vascular dementia typically occurs in patients with a history of

hypertension or other vascular risk factors.

b.

Alzheimer's disease

Alzheimer's disease usually has an insidious onset and gets worse very gradually.

c. Creutzfeld-Jakob disease

Creutzfeld-Jakob disease is a very rare cause of dementia that is characterised by

rapid deterioration and myoclonic jerking.

6.

A 70 year old woman with moderate Alzheimer's disease with a Mini Mental State

Examination score of 16 attends your clinic. Which of the following would be worthwhile?

a.

Memantine

b. Olanzapine

c. Donepezil

d.

Simvastatin

7. A 70 year old woman with moderate Alzheimer's disease with a Mini Mental State

Examination score of 16 attends your clinic. Which of the following would be worthwhile?


a Memantine b Olanzapine

c Donepezil


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d Simvastatin

10. Correct answer: Donepezil

a. Memantine

Recent guidance from the National Institute for Health and Clinical Excellence statesthat memantine is not recommended as a treatment option for any stage of

Alzheimer's disease unless used as part of a well designed clinical trial.

b. Olanzapine

The Medicines and Healthcare Regulatory Agency has recently stated that you

should not use olanzapine or risperidone for the behavioural symptoms of dementia

because of the increased risk of stroke.

c. Donepezil

While recent guidance has suggested that it is appropriate to use donepezil, a

cholinesterase inhibitor, in patients with moderate dementia (MMSE 10-20), this

would usually be initiated in a specialist care setting after assessment by either a

psychogeriatrician, neurologist, or geriatrician.

d. Simvastatin

There is a growing body of evidence to suggest that statins may retard or prevent the

pathogenesis and development of Alzheimer's disease. There have not been any

randomised clinical trials though to support this. Statins are therefore notrecommended at present as a primary treatment option for Alzheimer's disease.

7. You are asked to visit an 81 year old man with Alzheimer's disease who is living with his

daughter at her home. His mini mental state examination score is 9. His daughter is finding

it increasingly difficult to manage his behaviour since his risperidone was stopped. She is

asking you to represcribe this. What do you do?

a. Represcribe the risperidone

b. Prescribe olanzapine as an alternative

c. Assess the patient's surroundings and advise on non-pharmacological treatmentof behavioural problems in Alzheimer's disease

8. You are asked to visit an 81 year old man with Alzheimer's disease who is living with his

daughter at her home. His mini mental state examination score is 9. His daughter is finding

it increasingly difficult to manage his behaviour since his risperidone was stopped. She is

asking you to represcribe this. What do you do?

Your

answer

Correct

answer

a Represcribe the risperidone

b Prescribe olanzapine as an alternative

c Assess the patient's surroundings and advise on non-

pharmacological treatment of behavioural problems in Alzheimer's


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disease

11. Correct answer: Assess the patient's surroundings and advise on non-pharmacologicaltreatment of behavioural problems in Alzheimer's disease

a. Represcribe the risperidone




b. Prescribe olanzapine as an alternative




c.

Assess the patient's surroundings and advise on non-pharmacological treatment

of behavioural problems in Alzheimer's disease

You should exclude treatable causes (for example, physical illness and

environmental discomfort). You should offer carers education on non-

pharmacological measures such as maintaining a routine, providing a safe

environment (for example, with furniture and rugs), minimising excess stimulation

(for example, crowds and television) and ensuring comorbid conditions are treated(for example, check vision and hearing, and rationalise drugs). It may be appropriate

to refer the patient to social care for a further assessment of their needs to see if a

nursing home would be a more appropriate environment.

8.

A 59 year old woman attends your clinic concerned about occasional lapses of memory and

worried she has Alzheimer's disease. She has no significant medical history. What do you

advise?

a. Advise that memory loss is an inevitable part of ageing

b. Referral for genetic testing for the apolipoprotein E4 allele

c. Basic clinical examination and tests including a MMSE and thyroid function

tests

9. A 59 year old woman attends your clinic concerned about occasional lapses of memory and

worried she has Alzheimer's disease. She has no significant medical history. What do you

advise?

Your

answer

Correct

answer

a Advise that memory loss is an inevitable part of ageing

b Referral for genetic testing for the apolipoprotein E4 allele

c Basic clinical examination and tests including a MMSE and

thyroid function tests

12. Correct answer: Basic clinical examination and tests including a MMSE and thyroid

function tests


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a. Advise that memory loss is an inevitable part of ageing

The symptoms of Alzheimer's disease involve more than simple lapses of memory.

People with Alzheimer's disease also have difficulties in communication, learning,

thinking, and reasoning. Generally it is accepted that anyone can have occasional

lapses of memory provided they are not becoming more frequent over time oraffecting activities of daily living.

b. Referral for genetic testing for the apolipoprotein E4 allele

While the apolipoprotein E4 allele has been linked to Alzheimer's disease, genetic

testing is not currently recommended.

c. Basic clinical examination and tests including a MMSE and thyroid function

tests

Generally basic clinical assessment would take place in primary care initially with anassessment of cognitive functioning and memory using the MMSE. A score of >26

makes a diagnosis of Alzheimer's disease unlikely. Tests recommended and

supported by an evidence base include vitamin B12 levels and thyroid functions

tests. Hypothyroidism can cause impaired memory.

9. A 70 year old man with mild Alzheimer's disease visits your clinic with his wife. She is

concerned as he has lost interest in all his previous activities. He has become indifferent to

everything and says that life is not worth living. You suspect he has depression. What course

of action would you recommend?

a.

Start selective serotonin reuptake inhibitor

b. Start tricyclic antidepressant

c. Advise his wife that his symptoms are an inevitable consequence of Alzheimer's

disease and that nothing can be done

10. A 70 year old man with mild Alzheimer's disease visits your clinic with his wife. She is

concerned as he has lost interest in all his previous activities. He has become indifferent to

everything and says that life is not worth living. You suspect he has depression. What course

of action would you recommend?

Your

answer

Correct

answer

a Start selective serotonin reuptake inhibitor

b Start tricyclic antidepressant

c Advise his wife that his symptoms are an inevitable consequence

of Alzheimer's disease and that nothing can be done

11.

Correct answer: Start selective serotonin reuptake inhibitor

a. Start selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitors are the preferred treatment for depression.

They are usually well tolerated, although some patients experience sleep problems

and nausea.


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b. Start tricyclic antidepressant

Tricyclic antidepressants are poorly tolerated in old age as they cause a range of side

effects (for example, dry mouth and urinary retention). Fears exist that they can

accelerate cognitive loss due to their anticholinergic effects.

c. Advise his wife that his symptoms are an inevitable consequence of Alzheimer's

disease and that nothing can be done

Depressive symptoms are not an inevitable consequence of Alzheimer's disease and

these symptoms should be treated.

10. You are asked to see an 82 year old woman residing in a nursing home who was diagnosed

with Alzheimer’s disease four years ago. She has been stable with a MMSE score of 14/30

and well managed until recently when her carers have noticed that her behaviour is

becoming more aggressive and she is increasingly restless at night. What do you do first?

a. Prescribe risperidone to be given regularly

b. Prescribe a hypnotic to be given at night

c. Review patient’s medication and general health

d. Refer to a psychologist

11. You are asked to see an 82 year old woman residing in a nursing home who was diagnosed

with Alzheimer’s disease four years ago. She has been stable with a MMSE score of 14/30

and well managed until recently when her carers have noticed that her behaviour is

becoming more aggressive and she is increasingly restless at night. What do you do first?


a Prescribe risperidone to be given regularly

b Prescribe a hypnotic to be given at night

c Review patient’s medication and general health

d Refer to a psychologist

14. Correct answer: Review patient’s medication and general health

a. Prescribe risperidone to be given regularly

Guidelines recommend antipsychotics should only be prescribed after a full riskassessment has taken place and a regular monitoring plan established.

b. Prescribe a hypnotic to be given at night

Hypnotics should be used with caution in patients with dementia as they may worsen

the condition.

c. Review patient’s medication and general health

The patient should be assessed that no changes have been made recently to

medication or living conditions and that there is no other medical condition such asdepression, or physical health problem such as pain.


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d. Refer to a psychologist

While a psychological assessment may be appropriate in some patients with early

Alzheimer’s disease, this woman would probably not benefit as her condition is too

advanced.

References

1.

Department of Health. National service framework for older people. London: Stationery

Office, 2001.

2.

World Health Organization. Diagnostic and management guidelines for mental disorders in

primary care. London: Institute of Psychiatry, 2000. (Also available at

http://www.rsmpress.co.uk/bkwhopdf.htm )

3.

Ritchie K, Lovestone S. The dementias. Lancet 2002;360:1759-66.

4. Clark C, Jason H, Karlawash M. Alzheimer's disease: current concepts and emerging

diagnostic and therapeutic strategies. Ann Intern Med 2003;138:400-11.5. Cummings J, Cole G. Alzheimer disease. JAMA 2002;287:2335-8.

6.

McCormick A, Charlton J, Fleming D. Assessing health needs in primary care. Morbidity

study from general practice provides another source of information. BMJ 1995;310:1534.

7. Alzheimer's Disease International. Fact sheet 3. The prevalence of dementia. London:

Alzheimer's Disease International, 1999.

8. Crum RM, Anthony JC, Bassett SS, Folstein MF. Population-based norms for the Mini-

Mental State Examination by age and educational level. JAMA 1993;269:2386.

9. Wolf-Klein G, Silverstone F, Levy A, Brod M. Screening for Alzheimer's disease by clock

drawing. J Am Geriatr Soc 1989;37:730-6.

10. National Institute for Health and Clinical Excellence. Dementia. Supporting people with

dementia and their carers in health and social care. London: National Institute for Health andClinical Excellence, 2006.

11. Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, et al.

Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality

Standards Subcommittee of the American Academy of Neurology. Neurology

2001;56:1143.

12. Gifford D, Holloway R, Vickrey B. Systematic review of clinical prediction rules for

neuroimaging in the evaluation of dementia. Arch Intern Med 2000;160:2855.

13. Henderson A, Easteal S, Jorm A. Apolipoprotein E allele epsilon 4, dementia, and cognitive

decline in a population sample. Lancet 1995;346:1387.

14. National Institute for Clinical Excellence. Guidance on the use of donepezil, rivastigmine

and galantamine for the treatment of Alzheimer's disease. London: National Institute forClinical Excellence, 2001

15. McKeith I. The differential diagnosis of dementia. In: Burns A. Levy R. Dementia. London:

Chapman and Hall, 1994: 39-57.

16. Verghese J, Crystal HA, Dickson DW, Lipton RB. Validity of clinical criteria for the

diagnosis of dementia with Lewy bodies. Neurology 1999;53:1974-82.

17. First M, Frances A, Pincus H. DSM-IV-TR handbook of differential diagnosis. Arlington:

American Psychiatric Publishing, 2002.

18. Zubenko G, Zubenko W, McPherson S, Spoor E, Marin D, Farlow M, et al. A collaborative

study of the emergence of clinical features of the major depressive syndrome of Alzheimer's

disease. Am J Psychiatry 2003;160:811-4.

19.

Clare L, Woods JLT, Moniz Cook Ed, Orrell M, Spector A. Cognitive rehabilitation and

cognitive training for early stage Alzheimer's disease and vascular dementia. Cochrane

Database of Systematic Reviews 2003; (4): CD003260.

http://www.rsmpress.co.uk/bkwhopdf.htmhttp://www.rsmpress.co.uk/bkwhopdf.htmhttp://www.rsmpress.co.uk/bkwhopdf.htm


27/28

20. Avila R, Bottino C, Carvalhol I, Santos C, Miotto E. Neuropsychological rehabilitation of

memory deficits and activities of daily living in patients with Alzheimer's disease: a pilot

study. Braz J Med Biol Res. 2004; 37 (11): 1721-9.

21.

National Institute for Health and Clinical Excellence. Donepezil, Galantamine, Rivastimine

(review) and Memantine for the treatment of Alzheimer's disease. London: National

Institute for Health and Clinical Excellence, 2007.22. Birks J. Cholinesterase Inhibitors for Alzheimer's disease. Cochrane Database of Systematic

Reviews 2006; (1): CD005593

23. Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database

of Systematic Reviews 2006; (1): CD001190.

24. Wilcock GK, Lilienfeld S, Gaens E. Efficacy and safety of galantamine in patients with mild

to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine

International-1 Study Group. BMJ 2000;321:1445-9.

25. Loy C, Schneider L. Galantamine for Alzheimer's disease and mild cognitive impairment.

Cochrane Database of Systematic Reviews 2006; (1): CD001747.

26. Birks J, Grimley Evans J, Iakovidou V, Tsolaki M. Rivastigmine for Alzheimer's disease.

Cochrane Database Syst Rev 2000;(4):CD001191.27. Kaduszkiewicz H, Zimmerman T, Beck-Bornholdt H, van den Bussche H. Cholinesterase

inhibitors for patients with Alzheimer's disease: a systematic review of clinical trials. BMJ

2005; 331: 321-7.

28. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA

2001;286:208-16.

29. Birks J, Grimley Evans J, Van Dongen M. Ginkgo biloba for cognitive impairment and

dementia. Cochrane Database Syst Rev 2003;(2):CD001775.

30. Tabet N, Birks J, Grimley-Evans J, Orrell H, Spector A. Vitamin E for Alzheimer's disease.

Cochrane Database of Systematic Reviews 2000; (4): CD002854.

31. Petersen R, Thomas R, Grundman M, Bennett D, Doody R, Ferris S, et al. Vitamin E and

Donepezil for the treatment of Mild Cognitive Impairment. N Engl J Med 2005; 352: 2379-

2388.

32. Rockwood K. Epidemiological and clinical trials evidence about a preventive role for statins

in Alzheimer's disease. Acta Neurol Scand 2006; 114 (Suppl. 185): 71-77

33. North of England Evidence Based Guideline Development Project. The primary care

management of dementia. Newcastle upon Tyne: University of Newcastle upon Tyne, 1997.

34. Cummings J, Cherry D, Kohatsu N, Kemp B, Hewett L, Mittman B. Guidelines for

managing Alzheimer's disease: part II. Treatment. Am Fam Phys 2002;65:2263-72.

35. Audit Commission. Assistive Technology Independence and Well-being 4, 2004.

36. Department of health. Building telecare in England, London 2005.

37.

Thorgrimsen L, Spector A, Wiles A, Orrell M. Aroma therapy for dementia. Cochrane Database of Systematic Reviews 2003; (3): CD003150.

38. Ballard C, Hanney M, Theodoulou M, et al. The dementia antipsychotic withdrawal trial

(DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet

Neurology 2009; Early Online Publication, 9 January.

39. De Deyn PP, Rabheru K, Rasmussen A, Bocksberger JP, Dautzenberg PL, Eriksson S, et al.

A randomized trial of risperidone, placebo, and haloperidol for behavioural symptoms of

dementia. Neurology 1999;53:946-55.

40. Street JS, Clark WS, Gannon KS, Cummings JL, Bymaster FP, Tamura RN, et al.

Olanzapine treatment of psychotic and behavioural symptoms in patients with Alzheimer

disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. Arch

Gen Psych 2000;57:968-76.


28/28

41. Lanctot KL, Best TS, Mittmann N, Liu BA, Oh PI, Einarson TR, et al. Efficacy and safety

of neuroleptics in behavioural disorders associated with dementia. J Clin Psych

1998;59:550-61.

42.

Porsteinsson AP, Tariot PN, Erb R, Cox C, Smith E, Jakimovich L, et al. Placebo-controlled

study of divalproex sodium for agitation in dementia. Am J Geriatr Psychiatry 2001; 9:58-

66.43. Sival RC, Haffmans PM, Jansen PA, Duursma SA, Eikelenboom P. Sodium valproate in the

treatment of aggressive behaviour in patients with dementia-a randomised placebo

controlled clinical trial. Int J Geriatr Psychiatry 2002; 17:579-85.

44. Lyketsos C, Lee H. Diagnosis and Treatment of Depression in Alzheimer's Disease: A

Practical Update for the Clinician. Dementia and Geriatric Cognitive Disorders 2004;17:55-

64.

45.

Carnahan R, Lund B, Perry P, Chrischilles E. The Concurrent Use of Anticholinergics and

Cholinesterase Inhibitors: Rare Event or Common Practice? Journal of the American

Geriatric Society 2004; (52): 2082.

46. Wijeratne C. Review: pathways to morbidity in carers of dementia sufferers. Int

Psychogeriatr 1997;9:69-79.47. Passinet M, Stern Y. Prognostic factors. In: Gauthier S. Clinical diagnosis and management

of Alzheimer's disease. London: Martin Dunitz, 1999.

48.

Ritchie K, Lovestone S. The dementias. Lancet 2002;360:1759-66.

49. GP Committee of the BMA and the NHS Confederation. Investing in general practice: The

new general medical services contract. London: British Medical Association, National

Health Service Confederation, 2003. Revised and updated March 2006.

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