John O’Brien Institute for Ageing and Health Newcastle University and Northumberland, Tyne and Wear NHS Trust Making the diagnosis well: experience from the Newcastle Memory Service

Why diagnose dementia? Iliffe et al, 2003 Excluding remedial causes Excluding remedial causes Provides certainty, allows understanding Provides certainty, allows understanding Information about illness and prognosis Information 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 conditions and their treatment Allows search for common co-morbid symptoms and conditions and their treatment Medico-legal issues Medico-legal issues Early access to services/benefits Early access to services/benefits Wider benefits (planning services, research) Wider benefits (planning services, research)

Diagnosis of dementia is easy Myth

Diagnosis of dementia is not easy Fact

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

Diagnosis of dementia is not easy Fact Diagnosis of subtype of dementia is even more challenging

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

NINDS-AIREN Criteria for VaD (Roman et al, 1993) n Dementia (memory and 2 or more domains) n Cerebrovascular disease (focal neurology and CVD on brain imaging) n Link between the 2 (3 months or abrupt/fluctuating clinical course) n Possible VaD if brain imaging negative or relationship (3/12) not clear

NINDS Neuroimaging Criteria for VaD Topography Topography Large vessel strokes Large vessel strokes Extensive white matter change Extensive white matter change Lacunes (frontal/basal ganglia) Lacunes (frontal/basal ganglia) Bilateral thalamic lesions Bilateral thalamic lesions Severity Severity Large vessel lesion of dominant hemisphere Large vessel lesion of dominant hemisphere Bilateral strokes Bilateral strokes WML affecting >25% white matter (Price et al, 2005) WML affecting >25% white matter (Price et al, 2005)

Accuracy of DLB diagnosis SensitivitySpecificityPPV Mega et al Litvan et al Holmes et al Luis et al Lopez et al Verghese et al Hohl, et al McKeith et al Lopez et al Litvan et al. Mov Disord 2003; 18:

New Criteria for Probable DLB McKeith et al, Neurology, 2005 Cognitive decline sufficient to interfere with social/occupational function Cognitive decline sufficient to interfere with social/occupational function CORE features (at least one core + one suggestive or 2 core features must be present): CORE features (at least one core + one suggestive or 2 core features must be present): Fluctuation Fluctuation Recurrent visual hallucinations Recurrent visual hallucinations Spontaneous parkinsonism Spontaneous parkinsonism Suggestive features: Suggestive features: REM sleep behaviour disorder REM sleep behaviour disorder Neuroleptic sensitivity Neuroleptic sensitivity Dopaminergic abnormalities in basal ganglia on SPECT/PET Dopaminergic abnormalities in basal ganglia on SPECT/PET One core or suggestive feature sufficient for Possible DLB

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

n 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 n EEG and CSF measurement should not be used as routine investigations NICE/SCIE Guidelines

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

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

6-8 weeks later Case discussed at MDT Second appointment lasts mins: Patient and (usually) carer seen together Investigations explained Diagnostic disclosure started Management plan outlined Follow-up arrangements made 2. Review appointment

n n 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 n n Plus one or more of supportive features A. A.Presence of medial temporal lobe atrophy on MR B. B.Abnormal CSF biomarkers C. 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 AD Dubois et al, Lancet Neurology, 2007

n n Amyloid vaccination approaches »Active Aß immunization »Passive Aß immunization »Aß aggregation inhibitors n n Tau (TauRx, inhibits aggregation) n n Metal chelaters n n Anti-inflammatories n n Statins n n Dimebon Potential disease modifying treatments for AD

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

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