Down's syndrome and dementia

Down’s syndrome and dementia

Lisa R. Stanton and Rikus H. Coetzee

2004 10: 50-58
Adv. Psychiatr. Treat.
10.1192/apt.10.1.50
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Stanton & Coetzee
Advances in Psychiatric Treatment (2004), vol. 10, 50–58
Down’s syndrome and dementia
Lisa R. Stanton & Rikus H. Coetzee
Abstract Down’s syndrome is the most common genetic disorder seen in clinical practice: about 94% occurs
because of non-disjunction of chromosome 21 and 3–5% because of translocation. Individuals
increasingly survive to middle and old age, probably because of advances in medical treatment and
improved living conditions. People with Down’s syndrome have an increased risk of developing
Alzheimer’s disease in middle age. Within ICD–10 and DSM–IV classifications there is no consensus
on the diagnosis of dementia in people with learning disability. New treatments have been licensed
for use in mild to moderate Alzheimer’s disease (e.g. acetylcholinesterase inhibitors and memantine).
The comorbid picture of Down’s syndrome and Alzheimer’s disease presents a unique challenge to
the clinician in both diagnosis and management.
Epidemiology and aetiology
Neuropathology
Prevalence at birth of Down’s syndrome increases
Although senile plaques and neurofibrillary tangles
with maternal age, ranging from 0.7/1000 births for
may be widespread in the brains of people with
mothers aged 20–24 years to 55/1000 births for those
Down’s syndrome, not every affected individual
aged 45–49 years. The IQ of people with Down’s
develops Alzheimer’s disease. Alzheimer’s disease
syndrome is usually in the mild to moderately severe
is associated with characteristic neuropathological
range of the learning disability spectrum (IQ < 70).
changes in the brain, including the deposition of
The prevalence of Alzheimer’s disease in people
extracellular β-amyloid in neuritic plaques and the
with Down’s syndrome rises with increasing age,
formation of intracellular neurofibrillary tangles.
and prevalence rates varying from 6% to 75% have
These cause the death of the neurons that contain
been reported (Rabe et al, 1990; Visser et al, 1997). A
them (Wisniewski et al, 1985). These tangles comprise
recent study of 285 people with Down’s syndrome
neuronal inclusions of abnormal cytoskeletal
found a 13% prevalence of Alzheimer’s disease
components and abnormally phosphorylated tau
(Tyrell et al, 2001). Age-related cognitive decline and
protein. Increase in the number of plaques containing
frontal lobe dementia appear to be more prevalent
fibrillised b-amyloid is seen in people with Down’s
in the younger age groups (30–49 years of age), and
syndrome after the age of 50 years and is associated
frontal lobe dementia appears to be more prevalent
with neuronal loss. Presence of diffuse plaques,
in those with more severe learning disability, but
however, shows no such association with the onset
this needs to be confirmed by further studies
of Alzheimer’s disease (Schupf, 2002).
(Holland et al, 2000). It is possible that early-onset
The formation of β-amyloid occurs through the
cases present with more frontal symptoms and this
splitting of amyloid precursor protein coded for by
may represent a different clinical subtype of
a gene on chromosome 21. The β-amyloid is cleaved
Alzheimer’s disease in Down’s syndrome. There
to form the peptides AB1–40 and AB1–42. It is
appears to be no relationship between level of
thought that an important stage in the development
learning disability and risk of dementia or age at
of Alzheimer’s disease is deposition of AB1–42, and
onset of dementia (Holland et al, 1998). The rate of
this is associated with cognitive decline. Abnormal
deterioration appears to increase with age (Oliver
karyotypes that decrease the amyloid precursor
et al, 1998). The level of pre-existing cognitive
protein dose, for example translocations, are
function is also closely associated with the rate of
associated with a reduced risk of Alzheimer ’s
decline (Temple et al, 2001).
disease.
Lisa Stanton is a specialist registrar in old age psychiatry and general adult psychiatry in Nottingham (Nottinghamshire
Healthcare NHS Trust, Duncan Macmillan House, Porchester Road, Nottingham NG6 3AA, UK. E-mail:
Liza.Stanton@nottshc.nhs.uk). Her research interests are in liaison in old age psychiatry, the interface between old age psychiatry
and learning disability services, and neuropsychiatry. Rikus Coetzee is also a specialist registrar in general adult psychiatry
and old age psychiatry at Duncan Macmillan House, Nottingham. His research interests are in the treatment and epidemiology
of trauma-related neurosis in the elderly and the use of cognitive–behavioural therapy with elderly people.
50
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Down’s syndrome and dementia
The increased risk of dementia in people with
presentation. Difficulties with making a psychiatric
Down’s syndrome is thought to be associated with
diagnosis in a person with Down’s syndrome
overexpression of the amyloid precursor protein
include ‘psychosocial masking’. This refers to the
gene. However, there is a wide variation in the age
unsophisticated social skills and lack of life
at onset of dementia in people with Down’s
experiences that a person with learning disability
syndrome and this does not appear to be solely
might exhibit, which can alter the presentation of
attributable to overexpression of amyloid precursor
symptoms. People with Down’s syndrome may not
protein. Mutations in the genes for amyloid
present their symptoms verbally, because of their
precursor protein and presenilin 1 and 2 are
impaired communication skills. In fact, carers might
associated with familial Alzheimer’s disease, which
be more likely to highlight a change than would the
is often of early onset.
person with Down’s syndrome.
It is thought that people with Down’s syndrome
‘Diagnostic overshadowing’ (Reiss et al, 1982)
who have Alzheimer’s disease are similar to people
means the attribution of changes in behaviour or
with familial Alzheimer’s disease, in that the onset
ability to learning disability. For people with Down’s
of dementia is usually early. It should be noted that
syndrome, diagnostic overshadowing can mean
the mothers of individuals with Down’s syndrome
that they are referred to specialist services late or
seem to have a specific vulnerability to developing
not at all. When learning disability is present,
Alzheimer’s disease. A comprehensive review of the
diagnostic overshadowing seems to reduce the
genetic aspects of the disease in Down’s syndrome
significance attached to abnormal behaviour which
is given in Schupf et al (2001) and Schupf (2002).
might otherwise have been attributed to psychiatric
The early age at which people with Down’s
disorder. In addition, some abnormal behaviours
syndrome develop Alzheimer’s disease may be due
may be seen as less significant than the learning
to a variety of factors. Apolipoprotein E (ApoE) is a
disability itself. Taken to its fullest extent, the
polymorphic lipoprotein found in the brain. In
behaviour may be attributed solely to the intellectual
health, its role involves nerve sheath repair (Mann
impairment, rather than to a psychiatric disorder
et al, 1996). There are three common variants of
such as dementia.
the gene for APOE (alleles APOE ε2, APOE ε3 and
Another difficulty results from the exacerbation
APOE ε4). Numerous studies have shown that the
of cognitive deficits and maladaptive behaviours
presence of the ε4 allele is associated with early onset
that pre-date the dementia. This is known as
of Alzheimer’s disease, whereas the presence of the
‘baseline exaggeration’, and it can make determining
ε2 allele is associated with a delay in disease onset
the onset of dementia difficult in people with
and is possibly protective. The effects of the ε3 allele
learning disabilities. Finally, intellectual distortion
appear to lie somewhere between those of the ε4
(reduced abstraction) and often the reduced ability
and ε2 alleles. In women before the menopause,
to communicate clearly can lead to difficulty in
oestrogen promotes the growth and prolongs
identifying subjective symptoms.
survival of cholinergic neurons and has antioxidant
Even if a dementia is diagnosed it should be
properties. It also prevents formation of β-amyloid
remembered that changes in presentation might be
by regulating amyloid precursor protein metabolism.
due, or partially due, to social or emotional
Menopause occurs earlier in women with Down’s
difficulties.
syndrome (Seltzer et al, 2001). It is thought that the
loss of oestrogen may be important in the develop-
Presentation of dementia in Down’s
ment of Alzheimer’s disease in women, and women
treated with hormone replacement therapy (HRT)
syndrome
seem to have a markedly reduced risk of developing
Early-onset symptoms may vary from person to
the disease. However, HRT given to women with
person, but there is evidence that the acquisition of
cognitive impairment does not appear to prevent
deficits tends to mimic those seen in Alzheimer’s
further decline. It is unknown what the effect of HRT
disease generally (Oliver et al, 1998). Deterioration
might be in men.
in memory, learning and orientation tend to be
the first signs, and these symptoms are often
Clinical presentation
accompanied by increased dependence (Cosgrave
et al, 2000). Personality change is often associated
Potential difficulties in making
with early involvement of the frontal lobes (Holland
a diagnosis
et al, 2000). It has also been reported that Alzheimer’s
disease in Down’s syndrome presents with a greater
The clinical picture of Alzheimer ’s disease in
prevalence of low mood, excessive overactivity/
Down’s syndrome is complex, owing to the
restlessness, disturbed sleep, excessive uncooper-
pre-existing cognitive impairment and atypical
ativeness and auditory hallucinations (Cooper &
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Stanton & Coetzee
Prasher, 1998). Delusions and hallucinations do
augmented by robust caregiver interviews, pre-
occur in people with Down’s syndrome and
ferably with carers who observe the patient in
dementia, but they may be a less prominent feature
different settings, although it should be remembered
than in dementia alone. The reasons for this,
that informants might be unreliable. For example, a
however, remain unclear.
behaviour might be apparent in only one particular
It should be remembered that there is cognitive
setting. It is important to compare the patient’s
decline associated with ageing in Down’s syndrome.
current behaviour and functioning with that of the
Receptive and expressive language, short-term
past (longitudinal history). This might involve
memory and non-verbal reasoning can be preserved,
contacting previous carers (family or institution
but there are known to be slight declines in verbal
based) if the individual is currently in supported
and long-term memory for those over 50 years of age
living.
and the ability to form long-term memories and
Predisposing factors should be identified, as in
visuospatial construction may become slightly
any psychiatric history, for example a history of
impaired. For an individual who is developing
head injury or stereotypical head banging might be
dementia, however, there are significant deficits in
a risk factor for dementia. Assessing the mental state
learning and memory. It is important to correctly
is important to identify potential confounding
differentiate age-related cognitive decline from early
factors such as primary psychiatric illness and
dementia. It must, however, be kept in mind that for
treatable symptoms such as depression. The use of
people with Down’s syndrome over the age of 40,
decline in functioning is not inevitable. Box 1
summarises the clinical symptoms of Alzheimer’s
Box 1 Symptoms of dementia in Down’s
disease in Down’s syndrome.
syndrome
Cognitive
Investigation and differential
Forgetfulness of recent events (progressively
diagnosis
long-term)
Geographical disorientation
At present there is no generally accepted definition
Loss of previously learned skills
of Alzheimer’s disease in people with learning
Confusion
disability, although the diagnostic criteria for
Affective
psychiatric disorders for use with adults with
Low mood
learning disabilities (DC–LD; Royal College of
Insomnia/hypersomnia
Psychiatrists, 2001) include general criteria for the
Decreased concentration
diagnosis of dementia in learning disability using
Aggression and irritability
an axis classification. The DC–LD also differentiates
Anxiety and fearfulness
between Alzheimer’s disease, vascular dementia
Loss of interest and anergia
and delirium, but not dementia with Lewy bodies.
In addition, there must be no evidence for any other
Behavioural
cause of dementia on history and investigation.
Increased dependence
Consensus criteria for diagnosing dementia in
Social isolation
people with Down’s syndrome have been suggested
Excessive overactivity or restlesness
by a working group set up to establish such criteria
Excessive uncooperativeness
(Aylward et al, 1997). The group suggests that ICD–
Personality change
10 be used as a framework, because of its emphasis
Perceptual
on non-cognitive changes. Since diagnosing
Hallucinations in any modality
Alzheimer’s disease in Down’s syndrome can be
Neurological
complicated, it is important to be thorough and
Dysphasia leading to aphasia
comprehensive from the outset.
Agnosia
Apraxia
Assessment of the person with suspected
Gait disturbance
dementia
Seizures
Myoclonus
Full psychiatric, personal, past medical and family
Urinary incontinence
histories and mental state assessment are essential.
Dystonias
Attention should be paid to developmental, social
Loss of mobility
and medication histories. The history should be
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Down’s syndrome and dementia
psychopathology checklists should be encouraged,
these tests. For further information on test batteries
as this should capture all symptoms present, not
see Burt & Aylward (2000).
just those spontaneously reported by the patient or
It is also important to test thoroughly for sensory
carers.
impairment, because people with Down’s syndrome
When interviewing individuals with Down’s
may be unable to report such problems and it is
syndrome, consideration needs to be given to the
these that determine which test batteries can be
fact that they may have a short attention span and
performed. Sensory deficits can also mimic cognitive
may be suggestible, so that the answers they give
impairment (Aylward et al, 1997). It is important to
are those that they think you want to hear. Open
recognise both congenital and acquired sensory
questioning, with frequent recapping, is therefore
deficits, and this might require repeated testing
advised. There may be a discrepancy between the
over time.
patients’ understanding and how they express
themselves, so that they may appear to understand
Differential diagnosis
more than they actually do. This may be partly
due to the learning of various social phrases, which
When approaching the diagnosis of dementia in
they appear to use appropriately. People with
Down’s syndrome, it is of cardinal importance to
Down’s syndrome may rely on gestures and facial
rule out reversible causes of dementia and delirium.
expressions to help them understand the content of
This is especially the case with hypothyroidism. This
speech, and interviewers might need to accompany
group of patients is particularly vulnerable to
speech with gestures, signing or pictures.
physical illness that causes cognitive decline. It is
It is important to establish current abilities and
important to conduct a thorough physical and
compare these with the patient’s abilities at the best
neurological examination. It should be kept in mind
previous level of functioning, in order to identify
that neurological symptoms may present differently
any decline. Carers who have known an individual
in this group. For instance, apraxia may present as
for only a short period may be unaware that skills
an inability to dress or eat without assistance.
have been lost and may attribute the current level of
Agnosia may present as the inappropriate use of
functioning to the learning disability. It is also
everyday objects. Spatial disorientation may be
important to try to establish the time course and
evident from failures to locate familiar places in their
progression of any deterioration, as this is important
environment. Box 2 summarises the differential
diagnostically. A diagnosis of depression rather than
diagnosis of dementia in Down’s syndrome.
decline should be considered in the presence of
fluctuating symptoms.
Box 2 Differential diagnosis of dementia in
Test batteries for people with learning
Down’s syndrome
disabilities
Hypothyroidism
For someone with suspected dementia, it is useful
Sensory loss
to include in an assessment test batteries to establish
Depression
a baseline level of functioning. These tests can be
Sleep apnoea
repeated at intervals, which can be important when
Cognitive decline secondary to medication
evaluating the progression of the dementia and a
(particularly anticholinergics)
possible response to treatment. Tests would need to
Delirium (multitude of causes)
take into account the relatively low IQ range for
Chronic hepatitis
people with Down’s syndrome. For example, the Test
for Severe Impairment (Modified) (Albert & Cohen,
Changes in environment, bereavement
1992) and the Spatial Recognition Span (Moss et al,
Alzheimer’s disease
1986) require little or no speech. A useful scale is the
Vascular dementia
Dementia Scale for Down’s Syndrome (Gedye, 1995),
Dementia with Lewy bodies
as it is designed to measure early, middle and late
Neoplasms
stages of dementia. It includes the time course of the
Folic acid abnormalities (patients taking anti-
deterioration and a differential diagnosis scale. The
convulsants)
Dementia Questionnaire for Persons with Mental
Infection
Retardation (Evenhuis, 1996) has also gained
Other psychiatric disorders, e.g. anxiety and
prominence for use in this group. It is preferable
phobias
that a clinical psychologist with experience in
Abuse
assessing people with learning disabilities performs
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Stanton & Coetzee
physical factors. In the first instance, reversible
Box 3 Clinical investigations for dementia in
causes of cognitive decline must be identified and
Down’s syndrome
corrected as far as possible. These include physical
conditions such as delirium and hypothyroidism.
Full blood count
Baseline assessment of functioning should be
Urea and electrolytes
established for future reference.
Erythrocyte sedimentation rate and/or
Once a diagnosis of dementia is established it
C-reactive protein
is useful to distinguish the type of dementia:
Liver functions
Alzheimer’s disease is the most common. In Down’s
Thyroid functions
syndrome, dementia with Lewy bodies may present
Blood glucose
differently from Alzheimer’s disease. Depression,
Folate and B12
amotivational syndromes and psychotic symptoms
Computed tomography/magnetic resonance
may be more common in dementia with Lewy bodies
imaging of the brain
(Simard & Van Reekum, 2001). Patients with
Electrocardiogram
dementia with Lewy bodies are particularly prone
Chest X-ray
to adverse side-effects of psychotropic medication,
Electroencephalogram
especially typical antipsychotics, and atypicals may
Plasma levels of drugs such as digoxin and anti-
be better tolerated (Simard & Van Reekum, 2001).
convulsants
Alzheimer’s disease in Down’s syndrome can
Mid-stream urine test
present with cognitive, behavioural and psychiatric
Vision and hearing tests
symptoms. It is important to target the symptoms
being treated, so as not to exacerbate the patient’s
condition or cause harm through side-effects. People
Investigations for suspected dementia in Down’s
with learning disabilities are particularly prone to
syndrome are listed in Box 3, although clinicians
the side-effects of medication.
need to use their judgement as to what investigations
Increasingly, pharmacological treatment of the
an individual patient requires.
dementia is being considered. It is good practice in
Structural imaging of the brain could be useful in
individuals with learning disabilities and dementia
Down’s syndrome, although it is seldom diagnostic
to try to avoid the prescription of anticholinergic
in its own right. It should be kept in mind that many
agents, either alone or in combination. Individuals
people with Down’s syndrome have abnormal
with dementia are vulnerable to exacerbations in
scans. It is particularly useful for establishing the
their confusional states owing the anticholinergic
presence of vascular lesions, which aid in the
effects of many psychiatric drugs. It would be
differential diagnosis process. Studies using
advisable, in the first instance, to treat depression
computed tomography (CT) scanning show cerebral
with a selective serotonin reuptake inhibitor, as
atrophy in people with Down’s syndrome and
tricyclics are anticholinergic. Psychosis should be
dementia. Temporal-lobe-oriented CT scans show
treated with antipsychotics and, as mentioned
reduction in volume in the medial temporal lobe
above, it is preferable to use atypical agents, owing
(Lawlor et al, 2001). This may provide assistance
to their better side-effect profile and the association
in diagnosing Alzheimer ’s disease in Down’s
between Down’s syndrome and dementia with
syndrome. It is known that in the general popu-
Lewy bodies. Clinicians should always endeavour
lation, people who later develop Alzheimer’s disease
to use drugs with the fewest side-effects, as people
show atrophy in the medial temporal lobe. In
with learning disabilities may find it difficult to
Alzheimer’s disease, neuronal loss in the hippo-
report adverse effects and may have multiple
campus and amygdala is well recognised with
additional physical conditions. The behavioural and
reduced volumes on magnetic resonance imaging
psychological symptoms of dementia, although
(MRI) scans (Aylward et al, 1999). Computed
preferably handled by non-pharmacological means,
tomography scans may be better tolerated than MRI
can be treated as recommended for the general adult
by individuals with learning disabilities, because
population (Bouman & Pinner, 2002).
of the claustrophobic nature of MRI scanning.
Psychological assessment can be very useful,
both in identifying possible causes of behavioural
changes and in providing advice for their man-
Management
agement. Carbamazepine has been shown to
be beneficial in agitation and aggression and
When considering management of Alzheimer’s
benzodiazepines can also be used, bearing in mind
disease in people with Down’s syndrome it is
the potential risks of oversedation, falls and
important to take into account psychosocial and
tolerance.
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Down’s syndrome and dementia
Treatment of dementia in Down’s
more cognitive function. It is also important to
syndrome
remember that families caring for people with
Down’s syndrome and Alzheimer’s disease may
Direct treatment of the dementia itself remains
find it very difficult to consider moving them into
controversial in Down’s syndrome. There has been
residential care, owing to feelings of guilt. Carers
limited research showing that donepezil, an
must be supported when this decision has to be
acetylcholinesterase inhibitor, is effective in slowing
made.
the decline of functional ability in Alzheimer’s
Minimising their sensory deficits allows people
disease, but at this stage it is uncertain whether
with dementia to remain in their current environ-
similar gains could be achieved in Alzheimer’s
ment for as long as possible, by maximising their
disease associated with Down’s syndrome. There
ability to orient themselves and to communicate
has been some evidence that these agents may
effectively with their carers. Strategies to support
be useful in this group of patients (Prasher et al,
and maintain the strengths of the individual are
2002; Kishnani et al, 2001), although there have also
important and may necessitate modifications to the
been concerns that they may be poorly tolerated
environment. It can be helpful to encourage
(Hemingway-Eltomey & Lerner, 1999).
participation in as many activities as possible,
The consensus at present appears to be that acetyl-
although it is important that these do not exceed the
cholinesterase inhibitors should be considered and
individual’s abilities, as that might result in
that a very slow titration of the dose should be the
frustration and apparent decline in functioning.
norm (e.g. 5 mg donepezil daily for 4–6 weeks before
Regular small changes are preferable to infrequent
increasing the dose). It is known that optimum
large ones. Regular medical review can be helpful
benefits are gained from maximising the dose of
for monitoring mental state, thyroid and cardiac
acetylcholinesterase inhibitors. Donepezil appears
status, infections, anaemias and deteriorating
to be the only acetylcholinesterase inhibitor that has
sensory function, so that any abnormalities found
been systematically evaluated in Down’s syndrome,
can be treated.
but galantamine and rivastigmine are also available.
It should be noted that acetylcholinesterase
inhibitors are not licensed specifically for use in
people with a learning disability. However, this
Box 4 Cautions and contraindications of
is the case for many psychotropic agents, usually
acetylcholinesterase inhibitors in dementia
because learning disability is frequently an ex-
Cautions
clusion criterion for clinical trials (Fraser, 1999). The
Cardiac conduction abnormalities
contraindications for acetylcholinesterase inhibitors
Peptic ulceration
are listed in Box 4.
Urinary hesitancy and bladder outflow
obstruction
Physical and psychosocial factors
Chronic obstructive pulmonary disease and
asthma
Psychosocial interventions form a large part of the
Hepatic impairment
management of dementia in Down’s syndrome.
Gastrointestinal obstruction
Safety and stability of the individual’s environment
Renal impairment
are of the utmost importance. It has been shown that
the level of cognitive function has the greatest
Contraindications
association with decline and that, in turn, environ-
Pregnancy and breast-feeding
mental factors have the greatest impact on cognitive
Gastrointestinal bleeding
function (Temple et al, 2001). It might therefore hold
Drug interactions
true that environmental interventions increase
Antipsychotics, including chlorpromazine,
cognitive function, which in turn might ameliorate
clozapine, olanzapine and thioridazine,
the progression of the dementia.
because of their anticholinergic profile
The decision to move or not to move should be
Antidepressants, including the tricyclics,
carefully considered. Stability in the environment
paroxetine, fluoxetine, monoamine oxidase
helps to reduce confusion, and therefore carers and
inhibitors
location should not readily be changed. It is
Anticholinergics, including procyclidine,
recommended that individuals be maintained in
benzatropine, trihexyphenidyl/benzhexol,
their present environment for as long as is safely
orphenadrine, hyoscine
possible. Conversely, if they do have to be moved,
Suxamethonium
they are more likley to adapt to their new
Non-depolarising muscle relaxants
environment if this is done earlier, while they retain
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Stanton & Coetzee
Attention should also be paid to the needs of
Future developments
carers, to reduce carer burden. Carers and family
members sometimes report that they feel isolated
Several authors have suggested that baseline
and fearful of the likely impact of dementia on an
cognitive testing would be helpful for people with
individual with Down’s syndrome. Consideration
Down’s syndrome when they reach early adult-
of the psychological and practical needs of carers
hood. It would be advisable to ensure consensus
is vital. It is important to ensure good communi-
on which test batteries are used. Early adulthood
cation at every stage, and professionals might
has been suggested for baseline assessment, as
need to anticipate carers’ questions and concerns.
people with learning disability often continue to
Provision of written information on commonly
develop well into adulthood, and it is important
encountered problems in dementia might be
to ensure that the optimum level of achievement
helpful for carers, as might putting them into
has been attained when establishing a baseline.
contact with the Alzheimer’s Society (tel: 020 7306
If baseline testing were to become more wide-
0606; website: http://www.alzheimers.org.uk)
spread this would make it easier to identify decline
or the Down’s Syndrome Association (tel: 020 8682
if dementia is suspected later in life.
4001; website: http://www.downs-syndrome.
Much more research is needed in this field,
org.uk).
especially in the treatment of Alzheimer’s disease
Members of the community learning disability
in Down’s syndrome. Possible sites for interven-
team can provide advice for managing problems,
tion in Alzheimer’s disease include enhancement
and other members of the multi-disciplinary team
of cholinergic neurotransmission, neurotrans-
also give important support. Physiotherapists can
mitter substitution or modulation, modulation of
assist in mobility issues, and occupational
amyloid precursor protein processing, reduction
therapists in rehabilitation and preservation of
of tau hyperphosphorylation, ApoE modulation,
skills. Nursing staff (especially within the
modulation of glutaminergic neurotransmission
community learning disability team) have a great
and the use of neuronal growth factors.
deal to offer from the outset, but their role becomes
There is research ongoing that will investigate
more pronounced as dementia progresses and
the usefulness of anti-inflammatory drugs,
nursing care becomes more central. It is important
oestrogen and secretase inhibitors (which may
also to consider day care facilities or in-patient
prevent β-amyloid deposition, and hence halt
admission, but it should be remembered that
progression of Alzheimer’s disease). Vitamins C
moving the person into residential care might
and E, which are antioxidant, are being evaluated,
hasten functional decline and should be con-
and immunisation therapies may be on the
sidered a last resort.
horizon. Ampakines, which are active at excitatory
amino acid (glutamate) receptors, may enhance
Prognosis
synaptic response, possibly by slowing de-
activation. Piracetam, a nootropic, is being
The prognosis for dementia in general is poor and
evaluated as a drug that might improve cognitive
the presence of Down’s syndrome further compli-
impairment.
cates the situation. However, it should be kept in
The new addition of memantine (an N-methyl-
mind that many people with dementia, with or
D-aspartate receptor antagonist) for the treatment
without Down’s syndrome, lead full and meaning-
of moderate to severe Alzheimer ’s disease in the
ful lives despite cognitive decline. But dementia is
general population may very well spread to use
usually a progressive illness, and eventually it
in Alzheimer’s disease associated with Down’s
overtakes most people because of its complications.
syndrome. Initial data on elderly people show that
In the final stages, the individual’s physical health
memantine can bring benefits in activities of daily
needs may become paramount and require specialist
living and cognition, although evidence is at
care, which may include palliative care. The aim
present scanty.
of treatment at present involves slowing of and
There is already work ongoing into the prophy-
adaptation to decline, containment of distress and
lactic use of acetylcholinesterase inhibitors in
symptom relief rather than attempts to cure or
people with Down’s syndrome and Alzheimer ’s
reverse the condition. This means encouraging
disease, but more extensive evaluation of their use
continued social and occupational activities in
in this group will be required in the future. In
keeping with the individual’s changing abilities.
particular, multi-centre randomised controlled
Most patients die from the physical complications
trials with prolonged periods of follow-up are
of dementia such as respiratory tract infection and
needed to evaluate their effectiveness in Down’s
thromboembolism (Evenhuis, 1990).
syndrome.
56
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Down’s syndrome and dementia
Genetic screening for Alzheimer’s disease has
plaques in cases of Alzheimer ’s disease and hereditary
already been carried out successfully in the USA,
cerebral haemorrhage associated with mutations in the
APP gene. American Journal of Pathology, 148, 1257–
and it seems likely that improvements in this
1266.
technology will bring into clinical practice genetic
Moss, M. B., Albert, M. S., Butters, N., et al (1986)
screening for Alzheimer ’s disease in Down’s
Differential patterns of memory loss among patients
with Alzheimer ’s disease, Huntington’s disease, and
syndrome. Gene therapy and stem-cell trans-
alcoholic Korsakoff’s syndrome. Archives of Neurology,
plantation are also being evaluated, but any
43, 239–246.
effective clinical treatment is still some way off.
Oliver, C., Crayton, L., Holland, A., et al (1998) A four
year prospective study of age-related cognitive change
in adults with Down’s syndrome. Psychological Medicine,
References
28, 1365–1377.
Prasher, V. P., Huxley, A. & Haque, M. S. (2002) A 24-
Albert, M. & Cohen, C. (1992) The test for severe
week, double-blind, placebo-controlled trial of donepezil
impairment: an instrument for the assessment of
in patients with Down syndrome and Alzheimer ’s
patients with severe cognitive dysfunction. Journal of
disease. Pilot study. International Journal of Geriatric
the American Geriatric Society, 40, 449–453.
Psychiatry, 17, 270–278.
Aylward, E. H., Burt, D. B., Thorpe, L. U., et al (1997)
Rabe, A., Wisniewski, K. E., Schupf, N., et al (1990)
Diagnosis of dementia in individuals with intellectual
Relationship of Down’s syndrome to Alzheimer ’s
disability. Journal of Intellectual Disability Research, 41,
disease. In Application of Basic Neuroscience to Child
152–164.
Psychiatry (eds S. I. Deutsch, A. Weizman & R.
Aylward, E. H., Li, Q., Honeycutt, N. A., et al (1999) MRI
Weizman), pp. 325–340. New York: Plenum Press.
volumes of the hippocampus and amygdala in adults
Reiss, S., Levitan, G. W. & Szyszko, J. (1982) Emotional
with Down’s syndrome with and without dementia.
disturbance and mental retardation: diagnostic
American Journal of Psychiatry, 156, 564–568.
overshadowing. American Journal of Mental Deficiency,
Bouman, W. P. & Pinner, G. (2002) Use of atypical
86, 567–574.
antipsychotic drugs in old age psychiatry. Advances in
Royal College of Psychiatrists (2001) DC–LD [Diagnostic
Psychiatric Treatment, 8, 49–58.
Criteria for Psychiatric Disorders for Use with Adults with
Burt, D. B. & Aylward, E. H. (2000) Test battery for the
Learning Disabilities/Mental Retardation] (Occasional
diagnosis of dementia in individuals with intellectual
Paper OP48). London: Gaskell.
disability. Journal of Intellectual Disability Research, 44,
Schupf, N. (2002) Genetic and host factors for dementia
175–180.
in Down’s syndrome. British Journal of Psychiatry, 180,
Cooper, S. A. & Prasher, V. P. (1998) Maladaptive
405–410.
behaviours and symptoms of dementia in adults with
Schupf, N., Kapell, D., Nightingale, B., et al (2001)
Down’s syndrome compared with adults with intellec-
Specificity of the fivefold increase in Alzheimer ’s disease
tual disabilities of other aetiologies. Journal of Intellectual
in mothers of adults with Down syndrome. Neurology,
Disability Research, 42, 293–300.
57, 979–984.
Cosgrave, M. P., Tyrrell, J., McCarron, M., et al (2000) A
Seltzer, G. B., Schupf, N. & Wu, H. S. (2001) A prospective
five year follow-up study of dementia in persons with
study of menopause in women with Down syndrome.
Down’s syndrome: early symptoms and patterns of
Journal of Intellectual Disability Research, 45, 1–7.
deterioration. Irish Journal of Psychological Medicine, 17,
Simard, M. & Van Reekum, R. (2001) Dementia with Lewy
5–11.
bodies in Down’s syndrome. International Journal of
Evenhuis, H. M. (1990) The natural history of dementia in
Geriatric Psychiatry, 16, 311–320.
Down’s syndrome. Archives of Neurology, 47, 263–267.
Temple, V., Jozsvai, E., Konstantareas, M. M., et al (2001)
Evenhuis, H. M. (1996) Further evaluation of the Dementia
Alzheimer dementia in Down’s syndrome: the relevance
Questionnaire for Persons with Mental Retardation
of cognitive ability. Journal of Intellectual Disability
(DMR). Journal of Intellectual Disability Research, 40, 369–
Research, 45, 47–55.
3 7 3 .
Tyrell, J., Cosgrave, M., McCarron, M., et al (2001)
Fraser, B. (1999) Psychopharmacology and people with
Dementia in people with Down’s syndrome. International
learning disability. Advances in Psychiatric Treatment, 5,
Journal of Geriatric Psychiatry, 16, 1168–1174.
471–477.
Visser, F. E., Aldenkamp, A. P., Van Huffelen, A. C., et al
Gedye, A. (1995) Dementia Scale for Down’s Syndrome.
(1997) Prospective study of the prevalence of Alzheimer-
Manual. Vancouver, BC: Gedye Research and Consulting.
type dementia in institutionalized individuals with
Hemingway-Eltomey, J. M. & Lerner, A. J. (1999) Adverse
Down syndrome. American Journal on Mental Retardation,
effects of donepezil in treating Alzheimer ’s disease
101, 400–412.
associated with Down’s syndrome. American Journal of
Wisniewski, K. E., Wisniewski, H. M. & Wen, G. Y. (1985)
Psychiatry, 156, 1470.
Occurrence of neuropathological changes and dementia
Holland, A. J., Hon, J., Huppert, F. A., et al (1998)
of Alzheimer ’s disease in Down’s syndrome. Annals of
Population-based study of the prevalence and
Neurology, 17, 278–282.
presentation of dementia in adults with Down’s
syndrome. British Journal of Psychiatry, 172, 493–498.
Holland, A. J., Hon, J., Huppert, A., et al (2000) Incidence
and course of dementia in people with Down’s
Multiple choice questions
syndrome: findings from a population-based study.
Journal of Intellectual Disability Research, 44, 138–146.
1 People with Down’s syndrome:
Kishnani, P. S., Spiridigliozzi, G. A., Heller, J. H., et al
(2001) Donepezil for Down’s syndrome (comment).
a are at risk of developing early-onset Alzheimer’s
American Journal of Psychiatry, 158, 143.
disease
Lawlor, B. A., McCarron, M., Wilson, G., et al (2001)
b are at risk of developing dementia with Lewy bodies
Temporal lobe-oriented CT scanning and dementia in
c have senile plaques in middle age
Down’s syndrome. International Journal of Geriatric
d do not have neurofibrillary tangles in middle age
Psychiatry, 16, 427–429.
Mann, D. M., Iwatsubo, T., Ihara, Y., et al (1996)
e have mothers with an increased risk of Alzheimer’s
Predominant deposition of amyloid-beta 42(43) in
disease.
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57

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Stanton & Coetzee
2 As regards β-amyloid:
5 Cautions for acetylcholinesterase inhibitors
a it is formed by cleavage of amyloid precursor protein
include:
b it is cleaved to form AB1–40
a cardiac conduction abnormalities
c it is cleaved to form AB1–42
b hypothyroidism
d in the AB1–42 form it is implicated in the onset of
c hepatic impairment
Alzheimer’s disease
d peptic ulcer
e mutations in the amyloid precursor protein gene
e bladder outflow obstruction.
causing β-amyloid deposition are implicated in the
pathogenesis of familial Alzheimer’s disease.
3 Difficulties in diagnosing dementia in Down’s
syndrome:
a can be due to psychosocial masking
b can be reduced by diagnostic overshadowing
c can be due to impaired communication skills
d may be complicated by baseline exaggeration
e can be reduced by intellectual distortion, which helps
MCQ answers
in identifying subjective symptoms.
1
2
3
4
5
4 Affective symptoms of Alzheimer’s disease in
a T
a T
a T
a T
a T
Down’s syndrome include:
a low mood
b T
b T
b F
b T
b F
b insomnia
c T
c T
c T
c T
c T
c poor concentration
d F
d T
d T
d T
d T
d irritability
e T
e T
e F
e T
e T
e anergia.
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