Use of imaging in dementia

John O’Brien

Professor of Old Age Psychiatry

NIHR National Specialty Lead for Dementia

Department of Psychiatry

University of Cambridge

Brain imaging in dementia

• Rule out other brain disorders

• Assist with subtype diagnosis

• Stratify subjects for clinical trials/ treatments

• Outcome biomarker for clinical trials

• Investigate underlying neurobiology and

mechanismsResearch use

Clinical practice

Current imaging in Dementia

• Computed tomography (CT)

• Magnetic resonance imaging (MRI)

• Perfusion (HMPAO) SPECT

• Glucose (FDG) PET

• Dopamine (FP-CIT) SPECT

• Amyloid (PIB, florbetapir, flutemetamol, flurbetaben)

PET

• MIBG cardiac imaging

6/7 NICE Recommended

Dementia diagnosis in specialist dementia

diagnostic services

• Offer structural imaging to rule out reversible

causes of cognitive decline and assist with

subtype diagnosis, unless dementia is well

established and the subtype diagnosis is clear

• Do not rule out dementia based solely on the

results of CT or MRI scans

• Don’t forget coronal CT

(JOB recommended)

NICE Dementia guideline, June 2018 (www.nice.org.uk)

Diagnosing vascular dementia

• If the dementia subtype is uncertain and vascular

dementia is suspected, use MRI.

• Do not diagnose vascular dementia based solely

on vascular lesion burden

NICE Dementia Guideline, June 2018

Diagnosing Alzheimer’s disease

If the diagnosis is uncertain and Alzheimer’s disease is

suspected, consider either:

• FDG-PET (fluorodeoxyglucose-positron emission tomography)

- or perfusion SPECT (single-photon emission CT) if FDG-

PET is unavailable

or

• Examining CSF for phosphorylated-tau 181 and total tau and

either amyloid beta 1-42 or a ratio of amyloid beta 1-42 and

amyloid beta 1-40

NICE Dementia Guideline, June 2018

FDG

FDG

Consensus visual rating diagnosis

FDG-PET SPECT

Normal AD DLB Normal AD DLB

Actual

Clinical

Diagnosis

Control 27 1 2 21 0 9

AD 3 26 9 14 13 11

DLB 7 7 16 6 8 16

Dementia (AD/DLB) vs Control*

PET: Sensitivity 85% Specificity 90%

SPECT: Sensitivity 71% Specificity 70%

AD vs DLB

PET: Sensitivity 74% Specificity 70%

SPECT: Sensitivity 54% Specificity 67%

*p <0.05

O’Brien et al, Journal of Nuclear Medicine (2014)

Is PET more stressful than SPECT?

Bamford et al, 2015

0

10

20

30

40

50

60

70

80

90

100

Patients

Controls

Carers

Important factors associated with scan

Overall 97% rated PET and 91% SPECT as worthwhile

Bamford et al, 2015

Dopaminergic SPECT: a robust

biomarker for DLB

Pooled sensitivity 78%, specificity 90%

O’Brien et al, BMJ Open, 2014

Normal

DLB

Diagnosing dementia with Lewy bodies

• If the diagnosis is uncertain and dementia with Lewy

bodies is suspected, use 123I-FP-CIT SPECT

• If 123I-FP-CIT SPECT is unavailable, consider 123I-

MIBG cardiac scintigraphy

• Do not rule out dementia with Lewy bodies based

solely on normal results on 123I-FP-CIT SPECT or 123I-MIBG cardiac scintigraphy

NICE Dementia Guideline, June 2018

Diagnosing frontotemporal dementia

If the diagnosis is uncertain and frontotemporal

dementia is suspected, use either:

• FDG-PET or

• perfusion SPECT

Do not rule out frontotemporal dementia based

solely on the results of structural, perfusion or

metabolic imaging tests

NICE Dementia Guideline, June 2018

Amyloid imaging in Dementia

Negative scan:

normal

Positive scan:

Amyloid present

(AD, DLB, old age)

Flurbetapir

(Amyvid)

Flutametamol

(Vizamyl

Flurbetaben

(NeuraCeq)

3 commercially available Fluorine based ligands for AD diagnosis

What does NICE say about the use of

amyloid imaging?

NICE Dementia Guideline, June 2018

• 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

Evidence-based indications for PET-CT:

Amyloid imaging

May, 2016

Jansen et al, JAMA 2015

55 studies of 8694 people

Rates:

10% at 50 yo

20% at 70 yo

40% at 90 yo

Sevigny et al, Nature, 2016

ARIA:

5% - Placebo

6% - 1mg

13% - 3mg

37% - 6mg

47% - 10mg

Imaging tau: the AD and the FTD spectrum

TAU TDP-43

AD

Courtesy of Matthew Jones, from BAP

Dementia Guidelines: O’Brien et al, 2017

Leuzy et al, Mol Psych, 2019

Tau imaging with AV1451 in AD and PSP

Clearly differentiates AD from PSP with

differences in keeping with known and distinct

regional distributions

Passamonti, Vázquez Rodríguez et al, Brain 2017

Imaging tau: the AD and the FTD spectrum

TAU TDP-43

AD

Bevan-Jones et al, 2017

But how early do brain imaging changes occur?

The PREVENT-Dementia study

• 5 site study, Cambridge, Imperial, Oxford, Dublin,

Edinburgh

• Aim to recruit 600-700 cognitively normal 40-59 yo

• Half of group have FH dementia (parent)/ half do not

• Comprehensive assessment over 3-4 visits

− Baseline physical, cognition, blood, urine and saliva

− Multi-modal MR scan

− Optional: Lumbar puncture for CSF, Amyloid PET, 7T

MRI

• Follow-up at 2 and 5 years

Ritchie et al, Alz and Dementia, 2017

P<0.001

Mean age 53, mean age

parental dementia 72

JNNP, 2020

Conclusions

• CT, MR, perfusion SPECT and Glucose PET are

established clinical tools

• FP-CIT and MIBG (heart) can assist with DLB

diagnosis

• Amyloid imaging available, not yet in wide clinical use;

tau and other ligands in development

• Brain imaging changes can be detected years

(decades) before dementia onset

• When ordering scans don’t forget other aspects

(referral form, report, MDTs)

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