A Volume‐Based Alternative for classifying ATN: Data from the Tau Propagation over Time (T‐POT) cohort
A Volume‐Based Alternative for classifying ATN: Data from the Tau Propagation over Time (T‐POT) cohort
Background:Alzheimer’sdisease(AD)ischaracterizedbythecerebralaccumulationofamyloid-beta(A),tau(T),andprogressiveneurodegeneration(N).ThewidelyusedATNsystem,withregardtopositronemissiontomography(PET)biomarkers,catego-rizesADbasedonthemeansignalinspecificregionsofinterest(ROI).However,thisprocedure d...
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Personal Name(s): | Doering, Elena (Corresponding author) |
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Hönig, Merle C. / Dzialas, Verena / Lothmann, Julia / Giehl, Kathrin / Theis, Hendrik / Jäger, Elena / Andrassy, Gregory / Bauer, Andreas / Elmenhorst, David / Kroll, Tina / Matusch, Andreas / Krapf, Philip / Neumaier, Bernd / Lerche, Christoph / Tellmann, Lutz / Frensch, Silke / Zeyen, Philip / Sand, Frederik / Richter, Nils / Jessen, Frank / Onur, Oezguer A. / Ramirez, Alfredo / van Eimeren, Thilo / Drzezga, Alexander / Bischof, Gerard N | |
Contributing Institute: |
Kognitive Neurowissenschaften; INM-3 |
Published in: | Alzheimer's and dementia, 19 (2023) S24, S. e082991 |
Imprint: |
Hoboken, NJ
Wiley
2023
|
DOI: |
10.1002/alz.082991 |
DOI: |
10.34734/FZJ-2024-02273 |
Document Type: |
Journal Article |
Research Program: |
Multilevel Brain Organization and Variability |
Link: |
OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.34734/FZJ-2024-02273 in citations.
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. |