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?

• 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) status McCullagh 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

twisted fibres of tau protein that build up inside cells. are • Neocortical atrophy with neuronal loss • Synaptic loss • Neurochemical changes limbic regions.

– cholinergic deficits to cortical and

Diagnostic Triangle

History (Medical, Personal) Test Scores Presentation

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.

Problems with walking/balance

LATE ‘STAGE’

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. • 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) DS LD 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

Visuospatial skills Executive functions ADLs Language Memory Praxis Orientatio n Ability to organise life 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 – 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 & 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 6 12 months later.

104 people with DS on screening programme register 5 with Dementia 5 with concerns being investigated 92 no concerns

Age group

30-39 40-49 50-59 60+

National rates (from BPS/MRCPsych)

Up to 2% 10-25% 20-50% 30-75%

Plymouth rates

0 2/31 (7%) 1/18 (6%) 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

supporting the person with dementia.

for • 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 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?