Making the diagnosis well: experience from the Newcastle Memory Service

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

2. 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)

3. Diagnosis of dementia is easy Myth

4. Diagnosis of dementia is not easy Fact

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

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

7. 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

8. 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

9. 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 >25% white matter (Price et al, 2005)

10. 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; 18:467-486

11. 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

12. www.nice.org.uk

13. 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

14. 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

15. 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

16. 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

17. 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 • Addenbrooke’s Cognitive exam • Rey Auditory Verbal Learning Test • National Adult Reading Test (pre-morbid IQ)

18. 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

19. 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

20. 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)

21. 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

22. 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

23. THANK YOU j.t.o’brien@ncl.ac.uk