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@ARTICLE{Doering:1024599,
      author       = {Doering, Elena and Hönig, Merle C. and Dzialas, Verena and
                      Lothmann, Julia and Giehl, Kathrin and Theis, Hendrik and
                      Jäger, Elena and Andrassy, Gregory and Bauer, Andreas and
                      Elmenhorst, David and Kroll, Tina and Matusch, Andreas and
                      Krapf, Philip and Neumaier, Bernd and Lerche, Christoph and
                      Tellmann, Lutz and Frensch, Silke and Zeyen, Philip and
                      Sand, Frederik and Richter, Nils and Jessen, Frank and Onur,
                      Oezguer A. and Ramirez, Alfredo and van Eimeren, Thilo and
                      Drzezga, Alexander and Bischof, Gerard N},
      title        = {{A} {V}olume‐{B}ased {A}lternative for classifying {ATN}:
                      {D}ata from the {T}au {P}ropagation over {T}ime
                      ({T}‐{POT}) cohort},
      journal      = {Alzheimer's and dementia},
      volume       = {19},
      number       = {S24},
      issn         = {1552-5260},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {FZJ-2024-02273},
      pages        = {e082991},
      year         = {2023},
      abstract     = {Background:Alzheimer’sdisease(AD)ischaracterizedbythecerebralaccumulationofamyloid-beta(A),tau(T),andprogressiveneurodegeneration(N).ThewidelyusedATNsystem,withregardtopositronemissiontomography(PET)biomarkers,catego-rizesADbasedonthemeansignalinspecificregionsofinterest(ROI).However,thisprocedure
                      disregards the spatial extent of pathology and
                      neurodegeneration.
                      $Here,weproposeanalternativequantificationofthevolume,i.e.,fillstates,ofA,TandNin(pre)-clinicalAD.Method:WeanalyzeddatafromtheTauPropagationoverTime(T-POT)study,includ-ingcognitivelyunimpairedindividuals(CU,n=58),andpatientswithmildcognitiveimpairment(MCI,n=20)orADdementia(n=4).C11-PIB-PET(A),18F-AV1451(T)andperfusion-phase18F-AV1451scans(N)werespatiallyandintensity-normalized(reference:cerebellum).ToquantifythevolumeofA,TandN,wez-standardizedandsubsequentlybinarizedallscanswithin–modalityusingaz-scorethreshold.Fillstateswerethencomputedasthesumofabnormalvoxelsrelativetoawhole-brainmask.Finally,meanfillstateswerecomparedacrossgroupsofclinicalstatus(CU,MCI,AD)andpartialcorrelationsofeitherfillstatesormeanPETsignalinestablished,tracer-specificROIswithcognitiveperformance(MMSE)werecomputed,adjustingforage,sexandeducation.Result:Meanfillstatesreflectedclinicalstatus,astheyincreasedwithdiseaseprogres-sion(CU:A=4\%,T=4\%,N=3\%;MCI:A=15\%,T=11\%,N=4\%;ADdementia:A=20\%,T=23\%,N=5\%).Moreover,AandTfillstateswerenegativelyassociatedwithMMSE(rhoA=-.299,p<.001;rhoT=-.318,p<.01;rhoN=-.147,p=.20),whileassoci-Alzheimer’sDement.2023;19(Suppl.24):e082991.©2023theAlzheimer’sAssociation.1of2wileyonlinelibrary.com/journal/alzhttps://doi.org/10.1002/alz.0829912of2BIOMARKERSationsofmeanPETsignalandMMSEtendedtobeweaker(rhoA(global)=-.255,p=.03;rhoT(temporalmetaROI)=-.275,p=.01;rhoN(metaROI)=.179,p=.12).Conclusion:We$
                      present a competitive quantification scheme for ATN that is
                      asso-ciated with both, clinical status and cognitive
                      performance. These results, whilecurrently validated in a
                      larger sample, suggest that the spatiotemporal dynamics
                      ofpathologyandneurodegenerationintheADcontinuumarewellcapturedbyourmulti-parametricapproach,whichispossiblysuperiorcomparedtoclassificationfrommeanPETsignalintensity.},
      cin          = {INM-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {5251 - Multilevel Brain Organization and Variability
                      (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5251},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1002/alz.082991},
      url          = {https://juser.fz-juelich.de/record/1024599},
}