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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
