MRCPsych Training:
Down’s Syndrome
and Alzheimer’s
Disease
Once you’ve met one person with dementia….you’ve met
one person with dementia” Tom Kitwood
Dr Shelley Bevins, Clinical Psychologist
Lorna Rogers Community Nurse
Community Learning Disabilities Team, Plymouth
Community Healthcare, CIC
This morning
• What we hope to cover:
– What is dementia and why is it more
prevalent in people with Down’s syndrome?
– Assessment of dementia (including a brief
introduction to neuropsychological
assessment in people with LD)
– Supporting people with LD and dementia.
– Case vignettes
What do you know about
dementia?
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What are the symptoms?
Who is at risk?
Can it be treated?
Can it be cured?
Is there a test for it?
How long does it last?
DSM-IV definition of dementia
• Diagnostic features include : memory impairment and
at least one of the following: aphasia, apraxia,
agnosia, disturbances in executive functioning.
• In addition, the cognitive impairments must be severe
enough to cause impairment in social and
occupational functioning.
• Importantly, the decline must represent a decline
from a previously higher level of functioning.
• Finally, the diagnosis of dementia should NOT be
made if the cognitive deficits occur exclusively during
the course of a delirium.
What causes dementia?
• Cerebral cortical degeneration:
AD, LBD, FTD (behavioural and language variants)
• Subcortical degeneration:
PD, HD, CBD, PSP
• Toxic/metabolic disorders:
Alcohol, Vitamin B12 deficiency
• Cerebrovascular:
Multi-infarct dementia, Subcortical Ischemic Vascular
Disease, CADISIL
• Infections/inflammation:
CJD, MS, AIDS
• Neurological insult:
Tumour, hydrocephalus, brain injury, dementia pugilistica,
subdural haematoma.
Alzheimer’s
type
dementia
(50-70%)
Vascular
Dementia
(10-15%)
Lewy
Body
Dementia
(10%)
Frontotemporal
dementia
(9-12%)
Causes & Risk Factors
of dementia
• Age
• Gender (even when controlling for longevity).
Females increased AD likelihood, Males VD
• Vascular risk factors (smoking, vascular disease,
diabetes etc), even in AD
• Head Trauma
• Education (and head size) ? Cognitive reserve
• Family history
• Apolipoprotein E (ApoE) status
McCullagh et al., (2001)
Alzheimer’s Disease: Plaques
and Tangles
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? Cause or symptom
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Amyloid Plaques are deposits of
beta-amyloid protein that build up
in the spaces between nerve cells.
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Neurofibrillary Tangles are
twisted fibres of tau protein that
build up inside cells.
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Neocortical atrophy with neuronal
loss
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Synaptic loss
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Neurochemical changes –
cholinergic deficits to cortical and
limbic regions.
Diagnostic Triangle
History (Medical, Personal)
Presentation
Test Scores
Symptoms of Alzheimer’s Disease - ‘What to look out for’
EARLY ‘STAGE’
Loss of short-term
MID ‘STAGE’
memory
Language problems - naming objects,
Loss of daily living skills
maintaining conversation, understanding others.
Loss of sociability
Disorientation in time, place and person.
Loss of interest in favoured hobbies
Confusion.
Withdrawal of spontaneous communication
Loss of self-care / incontinence.
Disorientation / confusion
More severe changes in personality
Increased wandering
and social behaviour.
Onset of seizures
Irrational fears.
Verbal / physical aggression.
LATE ‘STAGE’
Problems with walking/balance
Seizure activity
Loss of eating/drinking/self-care skills
Severe intellectual deterioration
Marked personality and mood changes
Incontinence
Down’s Syndrome (DS)
• DS is the most common syndrome associated with
learning disabilities (20%).
• 95% of DS cases are Trisomy 21, 5% caused by
other abnormalities of chromosome 21
(translocation and mosaicism.)
• People with DS are at higher risk of Alzheimer’s
Disease at an earlier age than the general
population.
Down’s Syndrome & Dementia
• Increased life expectancy
• Link between chromosome 21
and amyloid production
Comparative Rates of Dementia Down’s syndrome, Learning disabilities, General Population
• Average age of onset is 55
years. 9 years (on average)
from diagnosis to death.
DS
LD
• Virtually all people with DS >40
years show characteristic brain
changes of AD - although not all
show clinical signs.
Cooper (reproduced in
BPS/RCP Guidance
2009)
GP
Why this risk?
• In DS, apoE4 protein (established risk factor) might
interact with A deposit, promoting amyloid
formation.
• This results in the development of plaques and
tangles as seen in AD.
• This build up is thought to be due to the over
expression of the A precursor gene on
Chromosome 21.
Differential Diagnosis
If not dementia, what could it be??
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Thyroid Disease
Depression & grief reactions
Sensory Impairment
Tumours
Vitamin B12
Acute confusional state (delirium, constipation,
infections, sodium levels, lack of sleep)
Environmental changes
Medication Side Effects
Subdural haematomas
Stroke
Brain Injury
Cervical Spine Instability
Alcohol & drugs
Epilepsy in dementia
Neuropsychology and
the Assessment and
Treatment
of Dementia
What is clinical neuropsychology?
•The study of brain-behaviour relationships
•Neurologists - how the brain is functioning
•Neuropsychologists - how the person is functioning
as a result of the brain changes.
Neuropsychological
Assessment
Reasons for a neuropsychological assessment in
learning disability work
• Baseline of functioning
• Monitoring change over time
• Differential and clinical diagnosis
• Specificity of diagnosis (type of dementia)
• Monitoring impact of medication
• Cognitive strengths and weaknesses - capacity
• Assessment of executive functioning
• Intervention planning
Neuropsychological Assessment
Visuospatial
skills
Executive functions
ADLs
Language
Memory
Praxis
Ability to organise
life
Orientation
Social skills
Neuropsychological assessment
of dementia (non LD)
• Screening tools include:
– AMTS, MMSE, ACE-R, CamCog, MEAMS, RBANs
– NART / WTAR (premorbid functioning)
• Further Assessments may include
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Estimates of premorbid level of functioning
Memory
Language
Executive functions
Attention & concentration
Visuospatial
IQ
Praxis
Neuropsychological Assessment
of dementia (LD)
The Plymouth Psychology dementia screen
• Review all file information
• Individual testing
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Verbal comprehension (and general verbal ability level)
Tests of visual memory
Naming
Orientation
Tests of planning and problem solving (new)
• With an informed carer
– Clinical interview
– Checklist of memory, mood, daily living skills & behaviour
(DLD)
– Life events scale
– Depression scale, if relevant
BPVS
Crayton & Oliver
Object Memory
Dementia in Learning Disabilities
(DLD)
• Formerly known as the DMR (Evenhuis et al., 2007).
• 50 item informant questionnaire.
• Eight sub-scales: short term memory, long term
memory, orientation (making up Sum of Cognitive
Scores), speech, practical skills, mood, activity and
interest and behavioural disturbance (making up Sum
of Social Scores).
• Problems with poor inter-rater reliability
• Cut off scores are available for probable dementia in
people with Down’s syndrome (separated into people
with mild, moderate and severe LD)
Frequency of screening
• Under 30 years: screen once.
• 40-49 years: every 2 years.
• 50 + years: annually.
• On anti-dementia drugs: screen every 6
months for as long as required.
• For non-DS, people are screened as and
when concerns arise and re-screened 612 months later.
104 people
with DS on
screening
programme
register
5 with
Dementia
92 no
concerns
5 with
concerns
being
investigated
Age
group
National rates (from
BPS/MRCPsych)
Plymouth
rates
30-39
Up to 2%
0
40-49
10-25%
2/31 (7%)
50-59
20-50%
1/18 (6%)
60+
30-75%
2/4 (50%)
Group Activity
• Derek Video
Interventions
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ACIs (Anti-dementia medications)
Environmental modification
Memory boxes/books
Communication passports
Training and education for individual, friends,
carers and family
• Individualised (person-centred) plans for
supporting the person with dementia.
• Health Action Plans & Annual Health Checks
Acetyl cholinesterase inhibitors
(AChIs)
• Donepezil (Aricept)
• Rivastigmine
• Galantamine
• Memantine – partial NMDA antagonist
Cholinergic hypothesis
• Levels of choline acetyltransferase activity reduces in
AD, DLB and Parkinson’s dementia.
• There is a correlation of cholinergic deficit with degree of
dementia and with pathological lesions (plaques)
• Acetylecholinesterase inhibitors prevent the breakdown
of acetylcholine postsynaptically by deactivating AChE –
thereby increasing ACh activity
Choline acetyltransferase
synthesises choline and
acetyl-coenzyme A into the
neurotransmitter
acetylcholine
Acetylcholinesterase (AChE)
breaks acetylcholine back
into acetate and choline
Efficacy of medications
• NICE guidelines (2011) recommend for mildmoderate AD.
• Small treatment effects on RCT studies in general
population (Cochrane, 2009).
• However, AD2000 (2004) study showed no benefit
from donepezil in a large RCT.
– Cognition averaged 0.8 MMSE points better
– Functional skills 1.0 BADLs point better
– No significant benefits in terms of institutionalisation or
progression of disability
– No difference in BPSD, carer distress, formal care costs,
unpaid caregiver time, adverse events or deaths
• Conclusion: “Donepezil is not cost effective, with
benefits below minimally relevant thresholds. More
effective treatments than Cholinesterase Inhibitors
are needed for Alzheimer's disease.”
In people with Down’s syndrome:
– Rivastigmine
• Less decline over 24 weeks in global
functioning and adaptive behaviours (Prasher
et al., 2005)
– Mixed results for Donepezil
• No improvement in cognition (Prasher et al.,
2002)
• Significant positive effects (Lott et al., 2002).
• Initial improvement in global functioning and
adaptive behaviours. Follow up at 104 weeks
significantly less ↓ in the treatment group
(Prasher et al., 2003)
Recap
• Recap on dementia, particularly AD, including
risk factors and neurodegenrative process
• Down’s syndrome and link between DS and
AD
• Neuropsychological assessment of dementia
in general and Down’s syndrome populations
• Interventions, including non-pharmacological
interventions
• ACIs and evidence for their use in DS
populations
Vignettes
Consider:
• What might be happening for the
Service User?
• What differential diagnoses might you
consider?
• What assessments would you want to
undertake?
• What would you do next?
• Who else would you involve?