E-ADNI (PharmaCog WP5) Italian ADNI. E-ADNI / PharmaCog WP5

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E-NI (PharmaCog WP5) Italian NI E-NI / PharmaCog WP5 DESIGN 1

E-NI / PharmaCog WP5 5 HV, T0 T1, scan rescan Within-site reproducibility (volume, thickness) Siemens Allegra 3T Average vol. change = 4.0 % Average thick. change = 4.8 % Siemens Trio 3T Average vol. change = 2.3 % Average thick. change = 2.8 % E-NI / PharmaCog WP5 5 HV, T0 T1, scan rescan Within-site reproducibility (volume, thickness) Literature* S. Allegra (n=5) S. Trio (n=5) Group average age (y) 69 ± 5 68 ± 10 74 ± 3 Percent reproducibility across sessions Hemispheric Averages Hippocampus 3.6 4.0 ± 5.4 2.3 ± 1.8 Thalamus 4.0 4.0 ± 3.0 3.9 ± 2.4 Caudate 2.0 2.7 ± 1.8 2.8 ± 1.8 Putamen 3.1 4.9 ± 3.6 6.0 ± 3.6 Pallidum 6.5 6.6 ± 6.5 5.7 ± 6.5 Amygdala 6.5 8.4 ± 1.1 7.8 ± 1.1 Lateral Ventricle 2.4 2.9 ± 2.3 1.8 ± 2.3 Jovicic et al., Neuroimage. 2009; 46:177 192 2

AIMS - - To disseminate the NI platform for structural MR data collection in Italy DESIGN - Cross sectional assessment of 400 consecutive patients with cognitive complaints - 9 academic memory clinics - 2-year project, 250k overall - Harmonization: installation of NI volumetric sequences + phantom acquisition WP1: Qualification MR scanners completed Center UO Scanner/Manufacturer Field Strenght Coils Qualification IRCCS Centro S. Giovanni di Dio, Brescia IRCCS Fondazione S. Lucia, Roma 1 GE Signa Excite 1.5T 8 channels head approved 2 Siemens Allegra 3T 8 channels head approved Fond. SDN Napoli 3 Philips Achieva 3T 8 channels head approved Università Campus Bio_Medico, Roma 4 Siemens, Avanto 1.5 T 8 channel head approved Università di Foggia 5 Siemens Sonata 1.5 T Body Coil approved Università di Firenze 6 Siemens synphony 1.5 T Bird Cage approved Fond. IRCCS Istituto Neurologico Besta 7 Siemens Avanto 1.5T 12 channels head approved Fond. IRCCS Mondino 8 Philips intera Gyroscan 1.5 T 8 channel head approved Università di Napoli 9 General Electrics 3T 8 channel head approved Centro Neurolesi "Bonino- Pulejo" 10 Siemens Sonata 1.5 T 8 channel head approved 3

- IRCCS S. Giovanni Dio -Brescia - IRRCS Besta -Milano - IRCCS Mondino- Pavia N=92 - IRCCS Santa Lucia - Uni Campus Biomedico ROMA N=93 - IRCCS SDN - II Uni Napoli NAPOLI N=109 Uni Foggia FOGGIA N=63 IRCCS Bonino Pulejo MESSINA N=38 Total subjects enrolled N=395 Subjects with Neuropsy N= 395 Subjects with FDG-PET N= 13 Subjects with MRI N=342 Subjects with EEG N=200 3 Tesla N= 136 1.5 Tesla N=206 MCI MSI FTD MCI FTD CTRL MCI SMI FTD CTRL 4

MRI QC 2% 10% 88% Low Quality Medium Quality High Quality 60 40 20 HQ: no artifacts, good G-W contrast, suitable for automated segmentation MQ: artifacts (e.g. head motion), suitable for manual segmentation only LQ: severe artifacts (e.g. incomplete brain coverage) UO1 UO2 UO3 UO4 UO5 UO7 UO8 UO9UO10 0 ITALIAN NI Stability of Total Intracranial Volume among scanners Scan 3T p> 0.05 Post-hoc Bonferroni Scan 1.5T p> 0.05 * Post-hoc Games Howell test 5

Core Clinical Features SMI (n=11) MCI (n=71) (n=164) FTD (n=14) SMI core features: No objective cognitive deficits 0 cognitive deficits 3 (27%) 9 (13%) 1 (1%) 0 1 or more cognitive deficits 7 (63%) 62 (87%) 163 (99%) 14 (100%) MCI core features: CDR score= 0.5 CDR=0 5 (50%) 0 1 0 CDR=0.5 5 (50%) 55 (88%) 39 (31%) 3 (21%) CDR>1 0 7 (11%) 86 (68%) 11(79%) core features: progressive deterioration, memory impairment plus other domains, functional deficits None 4 (40%) 10 (14%) 0 0 1 feature 5 (50%) 16 (23%) 14 (11%) 1(7%) 2 features 1 (10%) 23 (32%) 67 (53%) 12 (86%) All 3 0 13 (18%) 45 (36%) 1 (7%) FTD core features: language, behavioural and disinhibition problems None 9 (53%) 39 (59%) 65 (43%) 3 (21%) 1 feature 1 (6%) 14 (21) 53 (35%) 9 (64%) 2 features 0 0 0 1 (7%) All 3 0 0 0 0 ITALIAN NI AAIC 2012, Vancouver The Italian Alzheimer s Disease Neuroimaging Initiative (I-NI) Clinical Characterization and Methods Cavedo E. a, Babiloni C. b, Redolfi A. a, Lizio R. c, Chiapparini L. d, Sabatini U. e, Soricelli A. f, Vernieri F g., Sinforiani E. h, Tedeschi G. i, Marino S. l, Bruzzone MG d, Acquino D. d,, Alesiani M. e, Cherubuni A. e,salvatore E. i, Angeloni F. f, Scrascia F. g, Patrizia Chiarati h, Paolo Vitali h, Montella P i, Daniele Corbo i, Annalisa Baglieri, l Placido Bramanti l, Carducci F. m,carlo C. Quattrocchi n and Frisoni G.B. a a LENITEM Laboratory of Epidemiology, Neuroimaging, & Telemedicine - IRCCS Centro San Giovanni di Dio-FBF, Brescia, Italy b Department of Biomedical Sciences, University of Foggia, Foggia, Italy c IRCCS San Raffaele Pisana, Rome, Italy Roberta Lizio d Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy e Santa Lucia Foundation, Radiology Department, Rome, Italy f Fondazione SDN per la Ricerca e l Alta Formazione in Diagnostica Nucleare, IRCCS Naples, Italy g Neurol. University Campus Biomedico Rome, Italy h IRCCS C. Mondino National Institute of Neurology Foundation, Pavia, Italy.t i Department of Neurological Sciences, Second University of Naples, Naples, Italy l IRCCS Centro Neurolesi Bonino-Pulejo - Messina, Italy m Laboratory of Neuroimaging, Department of Physiology and Pharmacology, University of Rome Sapienza, Rome, Italy n IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy 6