1. AAN –Toronto, April 11, 2010 Development of a harmonized protocol for hippocampal tracing An EADC-ADNI joint effort INTRODUCTION

2. Structure: MR hippo volumetry Biochemistry: CSF tau/Abeta Function: FDG PET Amyloid deposits: PET BACKGROUND Hippocampal volume as a diagnostic marker Dubois, Feldman et al., Lancet Neurol 2007

3. Geuze et al., Mol Psychiatry 2005;10:147-59 Ref.Med border Lat border Inf border Norm. hippo vol (cm 3 ) LeftRight Watson et al. Mesial edge of temporal lobe Temp horn of lat ventr Incl subicular complex & uncal cleft w/ border separating subicular complex from parahippo gyrus 4.9035.264 Zipursky et al. Regional outline at choroidal fissure Not mentioned The interface of hippocampal tissue and parahippocampal gyrus white matter 1.9902.070 BACKGROUND The effect of segmentation protocols on hippocampal volume

4. BACKGROUND Hippocampal volume as an outcome measure in trials of disease modifiers DrugStudyEffectSegment. methodRef TramiprosateAlphase 68% (100 mg) 120% (150 mg) n.m.Gauthier et al., JNHA 2009 AtorvastatinADCLT “Chv* mm³ -134±174 vs - 583±354 p>.05” Manual protocol Insausti et al., 1998 AJNR; Machulda et al., 2001, Neuroimage Sparks et.a,l CCJM,2008 LEADe “significant at p<.05” MIDAS (semiautomated) Jones et al., Alz&Dem 2008 Feldman et al., Neurology 2010 AN1792 “Chv* % 3.78±2.63 vs 2.86±3.19 p = 0.124” Manual protocol Watson et al., 1992, Neurology Fox N et al., Neurology, 2005 Xaliproden Sanofi- Aventis Trials “significant atrophy” §n.m.From Vellas B et al. (Review), Lancet Neurol.,2008 Donepezil “p= 0.07” ε4 carriers only Manual protocol Jack et al., 1989;Radiology Jack et al., 2004; Neurology Jack CR et al., Neurobiol. Aging, 2008 * Chv= Change in hippocampal volume; § referenced link not working; n.m. = not mentioned

5. BACKGROUND Hippocampal volume (manual segmentation) as gold standard for automated segmentation algorithms Morey et al., NeuroImage 2009

6. To Harmonize Available Protocols for Manual Hippocampal Segmentation To Test the Validity of the Harmonized Protocol AIMS

7. F Barkhof/P ScheltensAmsterdam B Dubois/S LehericiParis N FoxLondon GB Frisoni Brescia H Hampel/J PantelFrankfurt A SimmonsLondon H SoininenKuopio S TeipelRostock LO WahlundStockholm THE WORKGROUP EADC

8. CR Jack Jr Rochester, MN G Barzokis UCLA, CA D Bennet Chicago, IL J Csernansky NorthW U, WA C DeCarli UC Davis, CA M De Leon New York, NY J Kaye Portland, OR R Killiany Boston USM, MA PM Thompson LoNI, UCLA, CA M Weiner/S Mueller UCSF/VAMC THE WORKGROUP ADNI

9. THE WORKGROUP other relevant hippo experts R CamicioliUniv Alberta, Canada J O’BrienNewCastle, UK J PruessnerMcGill, QC, Canada

10. EADC-ADNI P.I.s B VellasToulouse, France B WinbladStockholm, Sweden M WeinerUCSF, US Population-based studies M Breteler/ T Den HeijerRotterdam Scan Study P Sachdev/ JJ Maller PATH through life L LaunerNIA Bethesda W JagustBerkeley THE WORKGROUP Advisory Boards

11. Statistical Board S DuchesneLaval Univ, Canada L CollinsMNI, McGill, Montreal P PasqualettiAFaR, Rome Clinical Advisor PJ VisserMaastricht, The Netherlands Dissemination/Education G WaldemarCopenhagen, Denmark THE WORKGROUP Boards

12. Marina Boccardi psychologist, PhD Rossana Ganzola psychologist Enrica Cavedopsychologist Michela Pievanimathematician Anna Carolimathematician Alberto Redolfibioinformaticist THE WORKGROUP Personnel in Brescia