Biomarkers for dementia - ESNR in dementia - Barkhof .pdfNeuroimaging in Dementia, Springer 2011 FTLD –right sided Neuroimaging in Dementia, Springer 2011 FTLD pathology (Pick’s

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Neuroimaging in Dementia

Frederik Barkhof

Dept of Radiology & Nuclear Medicine

VUMC – Amsterdam – NL

Institutes of Neurology & Biomedical Engineering

UCL – London – UK

[email protected]; [email protected]

Outline

• Structural imaging in work-up of dementia

– systematic approach

• Atrophy patterns in AD, FTD

– regional atophy: beyond hippocampus

• Other neurodegenerative disorders

– dementia with parkinsonism, CJD

• Vascular co-morbidity versus VaD

– pattern of microbleeds

• Role of CSF and PET

– advanced MR techniques (ASL)

Work-up in suspected dementia

Neuroimaging in Dementia, Springer 2011

Routine MRI protocol Dementia

no contrast material injection

• 3D T1-weighted images (+ cor MPR)

– evaluation of the medial temporal lobe (MTA)

• axial FLAIR & T2 TSE

– hypoxic/ischaemic (white matter) pathology

• axial T2* gradient-echo (or SWI)

– detection of micro-bleeds and calcification

• DWI (Creutzfeld-Jacob)

Structured reporting – MRI

• Swelling

– Infection, paraneoplastic

• Primary GM loss

– AD, FTD, Parkinsonian syndromes

• Vascular pathology

– Infarcts, lacunes, WMC (CAA, CADASIL)

• Primary WM disease

– Leukodystrophies, MS, FXTAS,

Swelling - Herpes Simplex Encephalitis

*6674085 Neuroimaging in Dementia, Springer 2011

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Structured reporting – Swelling

• Neoplastic

– gliomatosis cerebri, intravascular lymphoma

• Autoimmune Limbic Encephalitis

– paraneoplastic, Hashimoto, VGKC, anti-NMDA

• Infections:

– PML, herpes

• NPH (rarely shunt-responsive)

• Vascular

– dural AVF, AVM

• RPLS/PRES

Swelling – Gliomatosis cerebri

Neuroimaging in Dementia, Springer 2011

Structured reporting – primary WM

• Infectious

– HIV, Whipple, syphilis

• Inflammatory

– MS, sarcoid, coeliac disease

• Leukodystrophy

– mitochondrial, peroxisomal

– FXTAS, vanishing white matter (VWM)

– adult polyglucogan body disease

• Toxic/metabolic

– CO, vitamin B, heroin

– delayed post-hypoxic demyelination

• Trauma

Primary WM – Vanishing White Matter

Neuroimaging in Dementia, Springer 2011

Structured reporting – primary GM

• Alzheimer

– mediotemporal, posterior variant

• FTD

– semantic, aphasic, frontal, right-temporal

• Parkinsonian

– DLB, PSP, MSA

• Other movement disorders

– Huntington, NBIA, Wilson

• Prion disease

– CJD, FFI, GSS

Amyloid and neurodegeneration

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Medial temporal lobe atrophy (MTA)

Wattjes, Radiology 2009

0 I II III IV

<75 years score > 1.5 abnormal

>75 years score > 2 abnormal

The Radiology Assistant

www.radiologyassistant.nl

Hippocampal volume – automated Hippocampal volume: age matters

van der Pol, Neurology 2006;66:236

MTA – unresolved issues

• Implementation of volumetric analysis

– better understanding of impact by scan quality

– move from workstations to scanner console

• Visual analysis: training of radiologists

– from training to certification?

• Interpretation issues

– normative data not standardized / available

• Integration with other data

– MRI: vascular burden, other ND features (including AD)

– non-imaging: CSF, genetic, clinical

FTLD – semantic

Neuroimaging in Dementia, Springer 2011

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Hippocampal atrophy - DD

Neuroimaging in Dementia, Springer 2011

FTLD – right sided

Neuroimaging in Dementia, Springer 2011

FTLD pathology (Pick’s disease)

Dementia with Parkinsonism

DLB normal hippo

PSP Humming bird

MSA hot-cross bun

Amyloid and dopamine PET

Burke JF, Brain 2011

DLB FTD AD

PIB Pittsburg compund B

(amyloid)

DTBZ di-hydro-tetra-benazine

(vesicular monamine)

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Presenile AD Patterns of atrophy - Alzheimer

• Medio-temporal

– Hippocampus, parahippocampus

– APOE-4 positive, senile age, memory

• Posterior pattern

– posterior cingulate, interparietal sulcus

– APOE-4 negative, presenile, visuo-spatial

• Atypical patterns

– frontal or occipital predominance (Benton)

– behavioral or visual symptoms

• DD with FTLD and DLB

Koedam E, Eur Radiology 2011

Posterior atrophy rating scale

*4467030

Posterior cortical atrophy

Male, 50 yr

Posterior/parietal atrophy - DD

Neuroimaging in Dementia, Springer 2011

Cortico-basal degeneration

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Structured reporting – Vascular

• Small vessel disease

– extensive WML, multiple lacunes

– specific diseases: CADASIL, CAA

• Large vessel pathology

– strategic infracts, dominant hemisphere

• Systemic causes of ischemia

– vasulitis

– mitochondrial

– post-hypoxic demyelination

VaD - NINDS-AIREN criteria

Van Straaten ECW, Stroke 2003 (Operational criteria)

LVD

dominant

hemisphere

SVD

>25% WM

involved

THAL

bilateral

medial lacunes

FLAIR misses thalamic lesions

Bastos-Leite, Stroke 2004

Vascular disease and dementia

• combination of infarcts & AD best predicts dementia

(Nun & MRC-CFAS studies)

– “double hit” concept

• WML stepping stone for clinical AD

– subclinical damage lowers threshold

• atherosclerosis accelerates AD pathology

• amyloid deposits in vessels & parenchyma

– lobar microbleeds in CAA and AD

– central MBs in hypertension

Pure VaD, no MTA

*0283537

MTA in VaD – mixed dementia

*0094523

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Cerebral microbleeds (SWI)

Goos J, Stroke 2009

Central Lobar

Anti-amyloid therapy – ARIA*

Before During After

*ARIA – Amyloid Related Imaging Abnormalities

Ostrowski S, Arch Neurol 2011

ARIA and amyloid-PET changes

Ostrowski S, Arch Neurol 2011

Alzheimer’s disease – treatment strategies

Mucke, Nature 2009

Rinne JO. Lancet Neurol 2010

Bapineuzimab – effect on 11C-PIB

BAP

PLC

Amyloid PET – MCI converters

Forsberg A, Neurobiol Aging 2008

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ADNI - PIB vs CSF Amyloid-

Penn Autopsy

Sample (56 AD, 52

Cog normal)

192 pg/ml

50.0

100

150

200

250

300

1 1.2 1.4 1.6 1.8 2 2.2 2.4

MCI

AD

Control

CS

F A 1

-42

Mean Cortical SUVR

Total N = 55 (11 Control, 34 MCI, 10 AD)

Courtesy W Jagust

MCI conversion in ADNI

Heister D, Neurology 2011

Frisoni GB. Nat Rev Neurol 2010

FDG-PET in AD – posterior cingulate

ASL – reduced perfusion in AD

Lower CBF in AD compared to MCI

(FWE p<0.05, corrected for age / sex)

Binnewijzend MAA, Radiology 2012

Decreased Default Mode Activity

Corrected for

age & gender

Corrected for

age, gender

and GM

volume

AD versus SMC p<0.05 FWE-corrected

Binnewijzend M, NBA 2011

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Stages of preclinical AD

Sperling RA, Alz & Dem 2011

Take home points

• Exclude structural lesions

– WM disease and swelling

• Neurodegeneration ~AD signature

– medio-temporal OR posterior cingulate

• Differential atrophy patterns

– FTD, PSP, MSA (DLB)

• VaD of vascular co-morbidity?

– separate target for Rx

• Functional PET/MRI techniques

– bridge gap between amyloid & atrophy

Thanks to Philip and Nick

Restaurant La Coupole @ ICAD 2011 in Paris