Neuroimaging in Dementia

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1 Outline Neuroimaging in Dementia Frederik Barkhof Dept of Radiology & Nuclear Medicine VUMC Amsterdam NL Institutes of Neurology & Biomedical Engineering UCL London UK 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 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 - Herpes Simplex Encephalitis Swelling Infection, paraneoplastic Primary GM loss AD, FTD, Parkinsonian syndromes Vascular pathology Infarcts, lacunes, WMC (CAA, CADASIL) Primary WM disease Leukodystrophies, MS, FXTAS, *

2 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 Structured reporting primary WM Primary WM Vanishing White Matter 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 Structured reporting primary GM Amyloid and neurodegeneration 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 2

3 Medial temporal lobe atrophy (MTA) The Radiology Assistant 0 I II III IV <75 years score > 1.5 abnormal >75 years score > 2 abnormal Wattjes, Radiology Hippocampal volume automated Hippocampal volume: age matters van der Pol, Neurology 2006;66:236 MTA unresolved issues FTLD semantic 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 3

4 Hippocampal atrophy - DD FTLD right sided FTLD pathology (Pick s disease) Dementia with Parkinsonism Amyloid and dopamine PET AD DLB FTD PIB Pittsburg compund B (amyloid) DLB normal hippo PSP Humming bird MSA hot-cross bun DTBZ di-hydro-tetra-benazine (vesicular monamine) Burke JF, Brain

5 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 Posterior atrophy rating scale Posterior cortical atrophy Koedam E, Eur Radiology 2011 Male, 50 yr * Posterior/parietal atrophy - DD Cortico-basal degeneration 5

6 Structured reporting Vascular VaD - NINDS-AIREN criteria 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 LVD dominant hemisphere SVD >25% WM involved THAL bilateral medial lacunes Van Straaten ECW, Stroke 2003 (Operational criteria) FLAIR misses thalamic lesions 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 Bastos-Leite, Stroke 2004 Pure VaD, no MTA MTA in VaD mixed dementia * *

7 Cerebral microbleeds (SWI) Anti-amyloid therapy ARIA* Central Lobar Before During After *ARIA Amyloid Related Imaging Abnormalities Goos J, Stroke 2009 Ostrowski S, Arch Neurol 2011 ARIA and amyloid-pet changes Alzheimer s disease treatment strategies Ostrowski S, Arch Neurol 2011 Mucke, Nature 2009 Bapineuzimab effect on 11 C-PIB Amyloid PET MCI converters BAP PLC Rinne JO. Lancet Neurol 2010 Forsberg A, Neurobiol Aging

8 CSF A /03/2018 ADNI - PIB vs CSF Amyloid- 300 Total N = 55 (11 Control, 34 MCI, 10 AD) MCI conversion in ADNI MCI 250 AD Control Penn Autopsy Sample (56 AD, 52 Cog normal) 192 pg/ml Courtesy W Jagust Mean Cortical SUVR Heister D, Neurology 2011 FDG-PET in AD posterior cingulate Frisoni GB. Nat Rev Neurol 2010 ASL reduced perfusion in AD Decreased Default Mode Activity Corrected for age & gender Lower CBF in AD compared to MCI (FWE p<0.05, corrected for age / sex) AD versus SMC p<0.05 FWE-corrected Corrected for age, gender and GM volume Binnewijzend MAA, Radiology 2012 Binnewijzend M, NBA

9 Stages of preclinical AD 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 Sperling RA, Alz & Dem 2011 Thanks to Philip and Nick Restaurant La ICAD 2011 in Paris 9