John O

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Making the diagnosis well experience from the
Newcastle Memory Service

• John OBrien
• Institute for Ageing and Health
• Newcastle University and Northumberland, Tyne and
  Wear NHS Trust

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Why diagnose dementia?Iliffe et al, 2003

• Excluding remedial causes
• Provides certainty, allows understanding
• Information about illness and prognosis
• Allows planning for future
• Appropriate subtype specific management
• Allows search for common co-morbid symptoms and
  conditions and their treatment
• Medico-legal issues
• Early access to services/benefits
• Wider benefits (planning services, research)

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Diagnosis of dementia is easy
Myth
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Diagnosis of dementia is not easy
Fact
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Why?

• Normal Ageing
• Mild Cognitive Impairment (MCI)
• Dementia
• Depression
• Anxiety
• Physical disorder
• Delirium
• Secondary to medication
• Other brain pathology (space occupying lesion)
• Etc

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Diagnosis of dementia is not easy
Fact
Diagnosis of subtype of dementia is even more
challenging
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DSM-IV Criteria for AD

• Development of multiple cognitive deficits
  manifested by both
• Memory impairment
• One or more of the following deficits (aphasia,
  apraxia, agnosia, disturbance in executive
  function)
• Deficits cause significant impairment in social
  and occupational functioning
• Represent a decline from previous level of
  functioning
• Not accounted for by another disorder

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NINDS-AIREN Criteria for VaD(Roman et al, 1993)

• Dementia (memory and 2 or more domains)
• Cerebrovascular disease (focal neurology and CVD
  on brain imaging)
• Link between the 2 (3 months or
  abrupt/fluctuating clinical course)
• Possible VaD if brain imaging negative or
  relationship (3/12) not clear

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NINDS Neuroimaging Criteria for VaD

• Topography
• Large vessel strokes
• Extensive white matter change
• Lacunes (frontal/basal ganglia)
• Bilateral thalamic lesions
• Severity
• Large vessel lesion of dominant hemisphere
• Bilateral strokes
• WML affecting gt25 white matter (Price et al,
  2005)

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Accuracy of DLB diagnosis

• Sensitivity Specificity PPV
• Mega et al. 1996 0.75 0.79 1.00
• Litvan et al. 1998 0.18 0.99 0.75
• Holmes et al. 1999 0.22 1.00 1.00
• Luis et al. 1999 0.57 0.90 0.91
• Lopez et al. 1999 0.00 1.00 0.00
• Verghese et al. 1999 0.61 0.84 0.48
• Hohl, et al. 2000 0.80 0.80 0.80
• McKeith et al. 2000 0.83 0.91 0.96
• Lopez et al. 2002 0.23 1.00 1.00

Litvan et al. Mov Disord 2003 18467-486
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New Criteria for Probable DLB McKeith et al,
Neurology, 2005

• Cognitive decline sufficient to interfere with
  social/occupational function
• CORE features (at least one core one suggestive
  or 2 core features must be present)
• Fluctuation
• Recurrent visual hallucinations
• Spontaneous parkinsonism
• Suggestive features
• REM sleep behaviour disorder
• Neuroleptic sensitivity
• Dopaminergic abnormalities in basal ganglia on
  SPECT/PET

One core or suggestive feature sufficient for
Possible DLB
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www.nice.org.uk
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NICE/SCIE Guidelines

• Comprehensive assessment, including
• history from patient and informant
• medication review
• mental state exam, including cognitive testing
• physical examination
• Investigations
• Routine blood screen
• HIV/ Syphilis if indicated
• MSU if delirium suspected
• CXR if indicated

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NICE/SCIE Guidelines

• Neuroimaging
• Structural imaging should be used to exclude
  other cerebral pathologies and to help establish
  the subtype diagnosis
• MRI is preferred modality to assist with early
  diagnosis and detect sub-cortical vascular
  changes, though CT can be used
• HMPAO SPECT should be used to help differentiate
  between AD, VaD and FTD if the diagnosis is in
  doubt
• FP-CIT SPECT should be used to help establish the
  diagnosis of DLB if the diagnosis is in doubt
• EEG and CSF measurement should not be used as
  routine investigations

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NICE/SCIE Guidelines

• A diagnosis of subtype of dementia should be made
  by healthcare professionals with expertise in
  differential diagnosis using standardised and
  validated criteria

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Newcastle Memory Clinic

• Currently 1-2 days/week
• Staffing
• Consultant and ST4-6 doctor sessions
• Psychologist and psychology assistant
• Clinic nurse
• OT
• Others as needed (e.g. speech therapy)
• Two stop shop

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1. Baseline appointment

• Basic screen (MMSE and routine bloods) before
  referral
• First appointment approx 1.5 hours
• Informant history
• Bristol Activities of Daily Living scale (BADL)
• Informant questionnaire on cognitive decline
  (IQCODE)
• Patient history
• Mental state
• Hospital anxiety and depression
• Focussed physical exam
• Basic cognitive testing
• Addenbrookes Cognitive exam
• Rey Auditory Verbal Learning Test
• National Adult Reading Test (pre-morbid IQ)

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Further investigations

• Further history/ information
• Other assessments
• Formal neuropsychological testing
• OT/ SW/ Speech and language
• Neurology/ geriatric medicine
• Investigations
• Neuroimaging (CT, MRI, SPECT)
• Other
• EEG/ ECG
• Other bloods
• Lumbar puncture

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2. Review appointment

• 6-8 weeks later
• Case discussed at MDT
• Second appointment lasts 30-45 mins
• Patient and (usually) carer seen together
• Investigations explained
• Diagnostic disclosure started
• Management plan outlined
• Follow-up arrangements made

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Proposed new diagnostic criteria for early
AD Dubois et al, Lancet Neurology, 2007

• Core diagnostic criteria
• Gradual and progressive change in memory function
  reported by patients or informants over more than
  6 months
• Objective evidence of significantly impaired
  episodic memory
• Plus one or more of supportive features
• Presence of medial temporal lobe atrophy on MR
• Abnormal CSF biomarkers
• Bilateral temporal/parietal hypo-metabolism on
  PET/ SPECT
• And other biomarkers as they are validated (e.g.
  Amyloid imaging)

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Potential disease modifying treatments for AD

• Amyloid vaccination approaches
• Active Aß immunization
• Passive Aß immunization
• Aß aggregation inhibitors
• Tau (TauRx, inhibits aggregation)
• Metal chelaters
• Anti-inflammatories
• Statins
• Dimebon

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Conclusions

• Specialist Memory Clinic/ Memory Assessment and
  Management Service (MAMS) has advantages
• Development of core team with expertise
• Structured environment/ protocol for assessment
• Facilitates standardisation of approach and
  multi-team working
• Easier access to investigations/ imaging when
  required
• Allows patient and carer to be assessed together
• Resource for teaching and research
• Focus for patient and carer centred education and
  training
• Hospital based service can have outreach
  (domiciliary) arm and vice versa
• Allows management to follow seamlessly from
  assessment and diagnosis
• A two stop shop is better than a one stop shop
• Try to future proof services against (or at least
  be aware of) possible future changes in diagnosis
  and management

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THANK YOU
j.t.obrien_at_ncl.ac.uk