Scb alzforum

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Scb alzforum

  1. 1. Samantha Burnham | Research Statistician17 June 2013CSIRO MATHEMATICS INFORMATICS AND STATISTICS | PREVENTATIVE HEALTHAIBL: A blood-based predictor forneocortical Aβ burden
  2. 2. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade, Clifford R Jack Jr, David SKnopman, et al. Lancet Neurol 2010; 9: 119–28The HypothesisBioinformatics and Biostatistics | Sam Burnham2 |
  3. 3. MotivationBioinformatics and Biostatistics | Sam Burnham3 |Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimers disease: a prospectivecohort study, V.L. Villemagne, S.C. Burnham, et al. Lancet Neurol 2013; 12 (4): 357-67
  4. 4. CohortsBioinformatics and Biostatistics | Sam Burnham4 |
  5. 5. MethodsBioinformatics and Biostatistics | Sam Burnham5 |NABDemographicsBloodMeasures=• SUVR• + vs -• Age• Gender• ...• Blood 1• Blood 2• ...• Blood 176Cross ValidateValidate• Base Model• Full modelCheck Value AddedRandom Forest
  6. 6. ResultsModel Markers AIBL Imaged CohortSens%(SD%)Spec%(SD%)AUC%(SD%)M1Age, APOE Genotype, CXCL-13, IgM-1, IL-17, PPY, VCAM-1, Aβ1-42, CDR sum of boxes79.6(1.3)82.4(1.2)87.6(0.7)M2Age, APOE Genotype, CXCL-13, IgM-1, IL-17, PPY, VCAM-1, Aβ1-4279.6(1.6)79.4(1.4)83.9(1.0)M3Age, CXCL-13, IgM-1, IL-17,PPY, VCAM-1, Aβ1-4273.2(1.8)73.3(1.8)80.8(1.7)M4Age, APOE Genotype, CDRsum of boxes71.4(1.1)71.5(1.1)78.3(0.8)M5 Age, CDR sum of boxes69.0(2.1)68.9(2.2)76.0(2.0)M6 Age, APOE Genotype66.7(1.6)66.7(1.6)70.2(1.3)Bioinformatics and Biostatistics | Sam Burnham6 |A blood-based predictor for neocortical Aβburden in Alzheimer’s disease: results fromthe AIBL study, S.C. Burnham, N.G. Faux, etal. Mol Psy 2013; doi:10.1038/mp.2013.40
  7. 7. ValidationModel Markers ADNI ImagedCohortSens%Spec%AUC%M1Age, APOE Genotype, CXCL-13,IgM-1, IL-17, PPY, VCAM-1, Aβ1-42, CDR sum of boxes78.3 76.3 84.7M2Age, APOE Genotype, CXCL-13,IgM-1, IL-17, PPY, VCAM-1, Aβ1-4273.9 74.6 81.7M3Age, CXCL-13, IgM-1, IL-17, PPY,VCAM-1, Aβ1-4268.1 73.6 68.8M4Age, APOE Genotype, CDR sumof boxes72.7 67.9 73.7M5 Age, CDR sum of boxes 59.1 62.3 64.5M6 Age, APOE Genotype 77.3 62.3 67.8Bioinformatics and Biostatistics | Sam Burnham7 |A blood-based predictor for neocortical Aβburden in Alzheimer’s disease: results fromthe AIBL study, S.C. Burnham, N.G. Faux, etal. Mol Psy 2013; doi:10.1038/mp.2013.40
  8. 8. Other SupportBioinformatics and Biostatistics | Sam Burnham8 |A blood-based predictor forneocortical Aβ burden inAlzheimer’s disease: resultsfrom the AIBL study, S.C.Burnham, N.G. Faux, et al. MolPsy 2013;doi:10.1038/mp.2013.40
  9. 9. Summary• Early detection is critical• Likely need multimodal and multistage screening process• Require cheap and non-invasive medium for widespread screen• Proof of principal for blood biomarker use• Composite scores, unlikely to be a single marker• Validation is imperativeBioinformatics and Biostatistics | Sam Burnham9 |
  10. 10. AcknowledgmentsBioinformatics and Biostatistics | Sam Burnham10 |AIBL is a large collaborative study and a complete listof contributors can be found at www.aibl.csiro.auAIBL is funded in part by a grant from the Science andIndustry Endowment Fund. We thank all who took partin the study.Acknowledgements andthanks to the AIBL studyparticipants and theirfamiliesDavid AmesArti AppannahMary BarnesKevin BarnhamJustin BedoShayne BellinghamLynette BonPierrick BourgeatBelinda BrownRachel BuckleySamantha BurnhamAshley BushGraeme ChandlerPrastishtha ChatterjeeKarren ChenRoger ClarnetteSteven CollinsIan CookeTiffany CowieKay CoxRhona CreeganEmily CuninghamDavid DarbyKarl DeruyckPatricia DesmondHang DingJames DoeckeVincent DoreHarriet DowningBelinda DridanKonsta DuesingDenise El- SheikhKathryn EllisMichael FaheyMaree FarrowNoel FauxMichael FenechJonathan FosterChristopher FowlerMaxime FrancoisJurgen FrippShaun FrostSam GardenerSimon GibsonDavid GothPetra GrahamVeer GuptaGarry HannanDavid HansenKarra HarringtonRichard HeadAndy HillMaryam HorMalcolm HorneBrenda HucksteppPete HudsonAndrew JonesGareth JonesAdrian KamerYogi KanagasingamMohan KarunanithiLisa KeamNeil KilleenAdam KowalczykDebra KrauseBetty KrivdicRebecca LachovitskiChiou Peng LamFiona LambNicola LautenschlagerSimon LawsWayne LeifertNat LenzoHugo LerouxFalak LftikharQiao-Xin LiFlorence LimYen Ying LimTeresa LinternLinda LockettKathleen LucasJames LuiLance MacaulayMark ManoGeorgia MartinsRalph MartinsPaul MaruffColin MastersYumiko MatsumotoSabine MatthaesSimon McBrideRachel McKayAndrew MilnerAlinda MondalClaire MontagueLynette MooreAudrey MuirRachel MulliganTabitha NashJulie NigroStewart NuttallNathan O’CallaghanChristopher O’HalloranGraeme OKeefeTim O’MearaKevin OngLisa OsborneChaoyi PangBernadette ParkerGlen PattenJeremiah PeifferSvetlana PejoskaLisa PennyKeyla PerezKelly PertilePramit PhalKerryn PikeStephanie Rainey-SmithParnesh RanigaAlan RembachCarolina RestrepoMalcolm RileyBlaine RobertsJo RobertsonMark RodriguesAlicia RooneyChristopher RoweRebecca RumbleTim RyanOlivier SalvadoIan SaundersGreg SavageBrendan SilbertHamid SohrabiJulie SyretteCassandra SzoekeKevin TaddeiTania TaddeiMichelle TeggPhilip ThomasDarshan TrivediBrett TrounsonAlison TuckfieldJose VargheseRobyn VeljanovskiGiuseppe VerdileVictor VillemagneIrene VolitakisMichael VovosStacey WalkerAndrew WattMike WeinbornAndrea WilsonBill WilsonMichael WoodwardOlga YastrubetskayaPaul YatesPing ZhangQing ZhangLuping Zhou

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