Journal Article

FZJ-2024-02273

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Volume‐Based Alternative for classifying ATN: Data from the Tau Propagation over Time (T‐POT) cohort

Doering, E. (Corresponding author) ; Hönig, M. C.FZJ* ; Dzialas, V. ; Lothmann, J. ; Giehl, K.FZJ* ; Theis, H. ; Jäger, E. ; Andrassy, G. ; Bauer, A.FZJ* ; Elmenhorst, D.FZJ* ; Kroll, T.FZJ* ; Matusch, A.FZJ* ; Krapf, P.FZJ* ; Neumaier, B.FZJ* ; Lerche, C.FZJ* ; Tellmann, L.FZJ* ; Frensch, S.FZJ* ; Zeyen, P. ; Sand, F. ; Richter, N.FZJ* ; Jessen, F. ; Onur, O. A. ; Ramirez, A. ; van Eimeren, T. ; Drzezga, A.FZJ* ; Bischof, G. N.FZJ*

2023
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.082991  doi:10.34734/FZJ-2024-02273

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.

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)

Appears in the scientific report 2024

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Database coverage:
; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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