AAN –Toronto, April 11, 2010

Development of a harmonized protocol for hippocampal tracing

An EADC-ADNI joint effort

INTRODUCTION

Structure:MR hippo volumetry

Alz

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ime

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Normal

CS

F t

ota

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u

CSF Abeta42

Biochemistry:CSF tau/Abeta

Function:FDG PET

Amyloid deposits:PET

BACKGROUNDHippocampal volume as a diagnostic marker

Dubois, Feldman et al., Lancet Neurol 2007

Geuze et al., Mol Psychiatry 2005;10:147-59

Ref. Med borderLat border

Inf border

Norm. hippo vol (cm3)

Left Right

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

4.903 5.264

Zipursky et al.

Regional outline at choroidal fissure

Not mentioned

The interface of hippocampal tissue and parahippocampal gyrus white matter

1.990 2.070

BACKGROUNDThe effect of segmentation protocols

on hippocampal volume

BACKGROUNDHippocampal volume as an outcome measure

in trials of disease modifiersDrug Study Effect Segment. method Ref

Tramiprosate Alphase 68% (100 mg)120% (150 mg)

n.m. Gauthier et al., JNHA 2009

Atorvastatin ADCLT “Chv* mm³ -134±174 vs -583±354 p> .05”

Manual protocolInsausti 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 2008Feldman et al., Neurology 2010

AN1792 “Chv* % 3.78±2.63 vs 2.86±3.19

p = 0.124”

Manual protocolWatson 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 protocolJack 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

BACKGROUNDHippocampal volume (manual segmentation)

as gold standard for automated segmentation algorithms

Morey et al., NeuroImage 2009

To Harmonize Available Protocols for Manual Hippocampal Segmentation

To Test the Validity of the Harmonized Protocol

AIMS

F Barkhof/P Scheltens Amsterdam B Dubois/S Leherici ParisN Fox LondonGB Frisoni BresciaH Hampel/J Pantel FrankfurtA Simmons LondonH Soininen KuopioS Teipel RostockLO Wahlund Stockholm

THE WORKGROUPEADC

CR Jack Jr Rochester, MNG Barzokis UCLA, CAD Bennet Chicago, ILJ Csernansky NorthW U, WAC DeCarli UC Davis, CAM De Leon New York, NYJ Kaye Portland, ORR Killiany Boston USM, MAPM Thompson LoNI, UCLA, CAM Weiner/S Mueller UCSF/VAMC

THE WORKGROUP ADNI

THE WORKGROUPother relevant hippo experts

R Camicioli Univ Alberta, CanadaJ O’Brien NewCastle, UKJ Pruessner McGill, QC, Canada

EADC-ADNI P.I.sB Vellas Toulouse, FranceB Winblad Stockholm, SwedenM Weiner UCSF, US

Population-based studiesM Breteler / T Den Heijer Rotterdam Scan StudyP Sachdev/ JJ Maller PATH through lifeL Launer NIA BethesdaW Jagust Berkeley

THE WORKGROUPAdvisory Boards

Statistical BoardS Duchesne Laval Univ, CanadaL Collins MNI, McGill, MontrealP Pasqualetti AFaR, Rome

Clinical AdvisorPJ Visser Maastricht, The Netherlands

Dissemination/EducationG Waldemar Copenhagen, Denmark

THE WORKGROUPBoards

Marina Boccardi psychologist, PhDRossana Ganzola psychologistEnrica Cavedo psychologistMichela Pievani mathematicianAnna Caroli mathematicianAlberto Redolfi bioinformaticist

THE WORKGROUPPersonnel in Brescia