Introduction, use of imaging and current guidelines. John O Brien Professor of Old Age Psychiatry University of Cambridge

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1 Introduction, use of imaging and current guidelines John O Brien Professor of Old Age Psychiatry University of Cambridge

2 Why do we undertake brain imaging in AD and other dementias? Exclude other causes for dementia Help confirm diagnosis - imaging biomarkers increasingly becoming part of clinical diagnostic criteria (but can t diagnose from the scan) Research enhance mechanistic understanding and as outcome measures for trials

3 Health warning No scan is diagnostic, like other tests and biomarkers are just a part of the jigsaw Dementia can be associated with normal scan Scans only as good as request And the report!

4 What is available for clinical imaging in Dementia? Computed tomography (CT) Magnetic resonance imaging (MRI) Perfusion (HMPAO) SPECT Glucose (FDG) PET Dopamine (FP-CIT) SPECT (for Lewy body dementia) Amyloid (florbetapir, flutemetamol, flurbetaben) PET

5 Computed Tomography (CT) Most widely available Relatively cheap (NHS Tariff 78, including report) Builds map based on electron density of brain Quick (5-60 secs on modern multislice scanners) Well tolerated Good resolution for Space Occupying Lesions, bone well visualised

6 Magnetic Resonance Imaging (MRI) Becoming more available More expensive (NHS Tariff 124, including report) Builds image based on proton density and proton response to magnetic excitation 5% subjects have claustrophobia Unsuitable for those with pacemakers Excellent anatomical resolution and sensitive for white matter pathology

7 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 Roman et al, 1993

8 Single Photon Emission Tomography (SPECT) Scanning Available with Gamma camera in District Hospital Slightly more expensive than MRI ( ) Image interpretation requires expertise Requires injection of radioactive tracer (eg Tc- HMPAO (Ceretec) or IMP for blood flow, FP-CIT (DaTSCAN) for dopamine transporter) HMPAO Distributes and fixes in brain proportional to blood flow (i.e. metabolism) Poor resolution (7-10mm)

9 Dopaminergic imaging, a biomarker for Lewy body dementia Phase 2 study of diagnosis (DLB v AD). Sens 78% Spec 90% Phase 3 Study (GE Healthcare funded). Similar diagnosistic accuracy in 40 sites Autopsy validation Use in possible cases Pooled data analysis C-PBB3 Licensed for clinical use in dementia in EU (2006) Walker et al, 2002; O Brien et al, 2004; McKeith et al, 2007; O Brien et al, 2009; Colloby et al, 2012; Walker et al, 2014; O Brien et al, 2014

10 NINCDS/ ADRDA Criteria for AD (Old) Dementia (2 or more cognitive deficits) Memory (new learning) impairment Impairment in social/ occupational functioning Progressive deterioration No disturbances of consciousness Onset Not accounted for by another brain disorder McKhann et al, 1984

11 Criteria for the diagnosis of very early Alzheimer s disease Gradual and progressive change in memory function reported by patients or an informant over more than 6 months Objective evidence of significantly impaired episodic memory m Plus at least one of: Medial temporal lobe atrophy on MR Bilateral temporal/parietal hypometabolism on PET/SPECT Amyloid positive PET imaging Abnormal CSF biomarkers (reduced A beta 42, raised tau / p-tau) International Working Group (IWG) Dubois B et al. Lancet Neurol 2007;6:734-46; Dubois B et al. Lancet Neurol 2010;9:

12 Alzheimer s and Dementia, 2011

13 Dementia with Lewy bodies Evidence of cognitive impairment (esp characteristic profile) of sufficient magnitude to interfere with normal social and occupational function Core features Fluctuating cognitive impairment 80% Recurrent complex visual hallucinations 70% Spontaneous features of parkinsonism 25-50% (75% eventually) Suggestive features REM sleep behaviour disorder Severe neuroleptic / antipsychotic sensitivity Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging McKeith et al. Diagnosis and management of dementia: Third Report of the DLB consortium. Neurology 2005

14 Canadian Consensus Conference on Dementia Not all subjects need structural imaging. A cranial CT scan is recommended if one or more of the following criteria are present: Age less than 60 years Rapid (eg over one to two months) unexplained decline Short duration of dementia (less than 2 years) Recent/significant head trauma Unexplained/ localising neurological symptoms History of cancer or use of anticoagulants or history of a bleeding disorder History of urinary incontinence and gait disorder early in the course of dementia Unusual or atypical cognitive symptoms or presentation Patterson et al, 2001

15 Practice parameter: diagnosis of dementia Structural neuroimaging with either a noncontrast CT or MR scan in the routine initial evaluation of patients with dementia is appropriate Linear or volumetric MR or CT measurement strategies for the diagnosis of AD are not recommended for routine use at this time For patients with suspected dementia, SPECT cannot be recommended for routine use in either initial or differential diagnosis as it has not demonstrated superiority to clinical criteria PET imaging is not recommended for routine use in the diagnostic evaluation of dementia at this time American Academy of Neurology, Knopman et al 2001

16 NICE/SCIE Dementia Guidelines (2006) 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 subcortical vascular changes, though CT can be used. Imaging may not always be needed in those presenting with moderate to severe dementia, if the diagnosis is already clear 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 Guideline currently under revision, due 2017

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18 Canadian Consensus Conference on Dementia Maintained guidance on not all subjects needing structural imaging, though it would be indicated in most. Suggested FDG PET (or perfusion SPECT if PET not available) if: After clinical assessment and structural imaging diagnosis is unclear and Diagnostic uncertainty is preventing appropriate management Support Appropriate use criteria for use of amyloid imaging Gauthier et al, 2012; Laforce et al, 2016

19 Evidence-based indications for PET-CT: 18F- Florbetapir Use in highly selected patients where: Alzheimer s dementia (AD) is a possible diagnosis but this remains uncertain after comprehensive evaluation by a dementia expert and conventional imaging work-up, and Knowledge of the presence or absence of amyloid is expected to increase diagnostic certainty and influence patient management Appropriate uses: unexplained dementia, unusual clinical presentation, very young age of onset Inappropriate uses: established AD, in those with no cognitive impairment or as a screening test November 2013

20 Last but very far indeed from least. Find out what imaging is available locally, and how to access it Try to get access to the actual images Put good quality information on the referral form, the reporting physician isn t telepathic.? Dementia not helpful Meet your reporting colleagues, both neuroradiology and nuclear medicine A joint MDT, even infrequently, has incredible value for clinical care, training and education and building relationship

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