John O’BrienJohn O’Brien Institute for Ageing and Health Institute for Ageing and Health

Newcastle University and Newcastle University and Northumberland, Tyne and Wear Northumberland, Tyne and Wear

NHS TrustNHS Trust

Making the diagnosis well: experience from the Newcastle

Memory Service

Why diagnose dementia?Why diagnose dementia?Iliffe et al, 2003Iliffe et al, 2003

• Excluding remedial causes Excluding remedial causes

• Provides certainty, allows understandingProvides certainty, allows understanding

• Information about illness and prognosisInformation about illness and prognosis

• Allows planning for future Allows planning for future

• Appropriate subtype specific management Appropriate subtype specific management

• Allows search for common co-morbid symptoms and Allows search for common co-morbid symptoms and conditions and their treatmentconditions and their treatment

• Medico-legal issues Medico-legal issues

• Early access to services/benefitsEarly access to services/benefits

• Wider benefits (planning services, research)Wider benefits (planning services, research)

Diagnosis of dementia is Diagnosis of dementia is easyeasy

MythMyth

Diagnosis of dementia is Diagnosis of dementia is not easynot easy

FactFact

Why?Why?

•““Normal Ageing”Normal Ageing”•Mild Cognitive Impairment (“MCI”)Mild Cognitive Impairment (“MCI”)•DementiaDementia•DepressionDepression•AnxietyAnxiety•Physical disorderPhysical disorder•DeliriumDelirium•Secondary to medicationSecondary to medication•Other brain pathology (space occupying lesion)Other brain pathology (space occupying lesion)•EtcEtc

Diagnosis of dementia is Diagnosis of dementia is not easynot easy

FactFact

Diagnosis of subtype of dementia Diagnosis of subtype of dementia is is

even more challengingeven more challenging

DSM-IV Criteria for AD DSM-IV Criteria for AD

Development of multiple cognitive deficits Development of multiple cognitive deficits manifested by bothmanifested by both– Memory impairmentMemory impairment– One or more of the following deficits (aphasia, One or more of the following deficits (aphasia,

apraxia, agnosia, disturbance in executive function)apraxia, agnosia, disturbance in executive function) Deficits cause significant impairment in social Deficits cause significant impairment in social

and occupational functioningand occupational functioning Represent a decline from previous level of Represent a decline from previous level of

functioningfunctioning Not accounted for by another disorderNot accounted for by another disorder

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

Dementia (memory and 2 or more Dementia (memory and 2 or more domains)domains)

Cerebrovascular disease (focal neurology Cerebrovascular disease (focal neurology and CVD on brain imaging)and CVD on brain imaging)

Link between the 2 (3 months or Link between the 2 (3 months or abrupt/fluctuating clinical course)abrupt/fluctuating clinical course)

PossiblePossible VaD if brain imaging negative or VaD if brain imaging negative or relationship (3/12) not clearrelationship (3/12) not clear

NINDS Neuroimaging Criteria NINDS Neuroimaging Criteria for VaDfor VaD

• TopographyTopography•Large vessel strokesLarge vessel strokes

•Extensive white matter changeExtensive white matter change

•Lacunes (frontal/basal ganglia)Lacunes (frontal/basal ganglia)

•Bilateral thalamic lesionsBilateral thalamic lesions

• SeveritySeverity•Large vessel lesion of dominant hemisphereLarge vessel lesion of dominant hemisphere

•Bilateral strokesBilateral strokes

•WML affecting >25% white matter WML affecting >25% white matter (Price et (Price et al, 2005)al, 2005)

Accuracy of DLB diagnosisAccuracy of DLB diagnosis

SensitivitySensitivity SpecificitySpecificity PPVPPV

Mega et al. 1996Mega et al. 1996 0.750.75 0.790.79 1.001.00

Litvan et al. 1998Litvan et al. 1998 0.180.18 0.990.99 0.750.75

Holmes et al. 1999Holmes et al. 1999 0.220.22 1.001.00 1.001.00

Luis et al. 1999Luis et al. 1999 0.570.57 0.900.90 0.910.91

Lopez et al. 1999Lopez et al. 1999 0.000.00 1.001.00 0.000.00

Verghese et al. 1999Verghese et al. 1999 0.610.61 0.840.84 0.480.48

Hohl, et al. 2000Hohl, et al. 2000 0.800.80 0.800.80 0.800.80

McKeith et al. 2000McKeith et al. 2000 0.830.83 0.910.91 0.960.96

Lopez et al. 2002Lopez et al. 2002 0.230.23 1.001.00 1.001.00

Litvan et al. Mov Disord 2003; 18:467-486Litvan et al. Mov Disord 2003; 18:467-486

New Criteria for Probable DLB New Criteria for Probable DLB McKeith et al, Neurology, 2005McKeith et al, Neurology, 2005

•Cognitive decline sufficient to interfere with Cognitive decline sufficient to interfere with social/occupational functionsocial/occupational function

•CORE features (at least one core + one CORE features (at least one core + one suggestive or 2 core features must be present):suggestive or 2 core features must be present):•FluctuationFluctuation

•Recurrent visual hallucinationsRecurrent visual hallucinations

•Spontaneous parkinsonismSpontaneous parkinsonism

•Suggestive features:Suggestive features:•REM sleep behaviour disorderREM sleep behaviour disorder

•Neuroleptic sensitivityNeuroleptic sensitivity

•Dopaminergic abnormalities in basal ganglia on Dopaminergic abnormalities in basal ganglia on SPECT/PETSPECT/PET

One core or suggestive feature sufficient for Possible DLB

www.nice.org.uk

Comprehensive assessment, including:Comprehensive assessment, including:– history from patient and informanthistory from patient and informant– medication reviewmedication review– mental state exam, including cognitive testingmental state exam, including cognitive testing– physical examinationphysical examination

InvestigationsInvestigations– Routine blood screenRoutine blood screen– HIV/ Syphilis if indicatedHIV/ Syphilis if indicated– MSU if delirium suspectedMSU if delirium suspected– CXR if indicatedCXR if indicated

NICE/SCIE GuidelinesNICE/SCIE Guidelines

NeuroimagingNeuroimaging– Structural imaging should be used to exclude other cerebral Structural imaging should be used to exclude other cerebral

pathologies and to help establish the subtype diagnosispathologies and to help establish the subtype diagnosis– MRI is preferred modality to assist with early diagnosis and detect MRI is preferred modality to assist with early diagnosis and detect

sub-cortical vascular changes, though CT can be used sub-cortical vascular changes, though CT can be used – HMPAO SPECT should be used to help differentiate between AD, HMPAO SPECT should be used to help differentiate between AD,

VaD and FTD if the diagnosis is in doubt VaD and FTD if the diagnosis is in doubt

– FP-CIT SPECT should be used to help establish the diagnosis of FP-CIT SPECT should be used to help establish the diagnosis of DLB if the diagnosis is in doubt DLB if the diagnosis is in doubt

EEG and CSF measurement should not be used as routine EEG and CSF measurement should not be used as routine investigationsinvestigations

NICE/SCIE GuidelinesNICE/SCIE Guidelines

NICE/SCIE GuidelinesNICE/SCIE Guidelines

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

Newcastle Memory ClinicNewcastle Memory Clinic

•Currently 1-2 days/weekCurrently 1-2 days/week

•Staffing:Staffing:•Consultant and ST4-6 doctor sessionsConsultant and ST4-6 doctor sessions

•Psychologist and psychology assistantPsychologist and psychology assistant

•Clinic nurseClinic nurse

•OTOT

•Others as needed (e.g. speech therapy)Others as needed (e.g. speech therapy)

•Two stop shopTwo stop shop

•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•Addenbrooke’s Cognitive exam

•Rey Auditory Verbal Learning Test

•National Adult Reading Test (pre-morbid IQ)

1. Baseline appointment1. Baseline appointment

•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

Further investigationsFurther investigations

•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

2. Review appointment2. Review appointment

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 featuresA. Presence of medial temporal lobe atrophy on MR

B. Abnormal CSF biomarkers

C. Bilateral temporal/parietal hypo-metabolism on PET/ SPECT

And other biomarkers as they are validated (e.g. Amyloid imaging)

Proposed new diagnostic criteria for early ADProposed new diagnostic criteria for early ADDubois et al, Lancet Neurology, 2007

Amyloid vaccination approaches» Active Aß immunization Active Aß immunization » Passive Aß immunizationPassive Aß immunization» Aß aggregation inhibitorsAß aggregation inhibitors

Tau (TauRx, inhibits aggregation) Metal chelaters Anti-inflammatories Statins Dimebon

Potential disease modifying treatments for ADPotential disease modifying treatments for AD

ConclusionsConclusions

• Specialist Memory Clinic/ Memory Assessment and Specialist Memory Clinic/ Memory Assessment and Management Service (MAMS) has advantages:Management Service (MAMS) has advantages:

•Development of core team with expertiseDevelopment of core team with expertise•Structured environment/ protocol for assessmentStructured environment/ protocol for assessment•Facilitates standardisation of approach and multi-team workingFacilitates standardisation of approach and multi-team working•Easier access to investigations/ imaging when requiredEasier access to investigations/ imaging when required•Allows patient and carer to be assessed togetherAllows patient and carer to be assessed together•Resource for teaching and researchResource for teaching and research•Focus for patient and carer centred education and trainingFocus for patient and carer centred education and training•Hospital based service can have outreach (domiciliary) arm and vice Hospital based service can have outreach (domiciliary) arm and vice

versa versa •Allows management to follow seamlessly from assessment and diagnosisAllows management to follow seamlessly from assessment and diagnosis

• A two stop shop is better than a one stop shopA two stop shop is better than a one stop shop

• Try to future proof services against (or at least be aware of) Try to future proof services against (or at least be aware of) possible future changes in diagnosis and managementpossible future changes in diagnosis and management

THANK YOUTHANK YOUj.t.o’brien@ncl.ac.ukj.t.o’brien@ncl.ac.uk