MRCPsych Training:Down’s Syndrome and Alzheimer’s

Disease

Dr Shelley Bevins, Clinical PsychologistLorna Rogers Community Nurse

Community Learning Disabilities Team, Plymouth Community Healthcare, CIC

Once you’ve met one person with dementia….you’ve met one person with

dementia” Tom Kitwood

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?

• 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%)

Fronto-temporal 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) statusMcCullagh et al., (2001)

Alzheimer’s Disease: Plaques and Tangles

• ? Cause or symptom

• Amyloid Plaques are deposits of beta-amyloid protein that build up in the spaces between nerve cells.

• Neurofibrillary Tangles are twisted fibres of tau protein that build up inside cells.

• Neocortical atrophy with neuronal loss

• Synaptic loss

• Neurochemical changes – cholinergic deficits to cortical and limbic regions.

Diagnostic Triangle

History (Medical, Personal)History (Medical, Personal)

PresentationPresentation Test ScoresTest Scores

Symptoms of Alzheimer’s Disease - ‘What to look out for’EARLY ‘STAGE’

Loss of short-term

memory

Loss of daily living skills

Loss of sociability

Loss of interest in favoured hobbies

Withdrawal of spontaneous communication

Disorientation / confusion

Increased wandering

Onset of seizures

MID ‘STAGE’

Language problems - naming objects,

maintaining conversation, understanding others.

Disorientation in time, place and person.

Confusion.

Loss of self-care / incontinence.

More severe changes in personality

and social behaviour.

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

• Average age of onset is 55 years. 9 years (on average) from diagnosis to death.

• Virtually all people with DS >40 years show characteristic brain changes of AD - although not all show clinical signs.

Comparative Rates of Dementia -Down’s syndrome, Learning disabilities, General Population

Cooper (reproduced in BPS/RCP Guidance 2009)

DSLD

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??

• 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

Orientation

ADLs

Social skills

Ability to organise life

LanguageMemory

Praxis

Visuospatial skills

Executive functions

Neuropsychological assessment of dementia (non LD)

• Screening tools include:– AMTS, MMSE, ACE-R, CamCog, MEAMS, RBANs– NART / WTAR (premorbid functioning)

• Further Assessments may include– 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

– 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 & OliverObject 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 6-12 months later.

104 people with DS on screening

programme register

5 with Dementia

92 no concerns

5 with concerns

being investigate

d

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

• 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

• Donepezil (Aricept)

• Rivastigmine

• Galantamine

• Memantine – partial NMDA antagonist

Acetyl cholinesterase inhibitors (AChIs)

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 mild-

moderate 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?