2023
Spatiotemporal Correlation between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging
Kim C, Diez I, Bueichekú E, Ahn S, Montal V, Sepulcre J. Spatiotemporal Correlation between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging. Journal Of Neuroscience 2023, 44: e0488232023. PMID: 38123362, PMCID: PMC10869152, DOI: 10.1523/jneurosci.0488-23.2023.Peer-Reviewed Original ResearchMeSH KeywordsAgedAgingAlzheimer DiseaseAmyloidAmyloid beta-PeptidesCognitionCognitive DysfunctionHumansPositron-Emission TomographyTau ProteinsConceptsHarvard Aging Brain StudyCognitive changesCognitive declineAssociated with cognitive changesAssociated with early cognitive declineAging Brain StudyEarly cognitive declineTau depositionCognitive scoresBrain studiesHuman brainTau pathologyOlder adultsTau accumulationTau associationImpaired associationAD symptomsClinical trajectoryCortical patternsTauBraak stageSpatiotemporal levelsTemporal accumulationBraakFuture increasesAssociation of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults
Hanseeuw B, Jacobs H, Schultz A, Buckley R, Farrell M, Guehl N, Becker J, Properzi M, Sanchez J, Quiroz Y, Vannini P, Sepulcre J, Yang H, Chhatwal J, Gatchel J, Marshall G, Amariglio R, Papp K, Rentz D, Normandin M, Price J, Healy B, El Fakhri G, Sperling R, Johnson K. Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults. Neurology 2023, 101: e2533-e2544. PMID: 37968130, PMCID: PMC10791053, DOI: 10.1212/wnl.0000000000207962.Peer-Reviewed Original ResearchConceptsAssociated with cognitive declineOlder adultsNon-AD pathologyCognitive declineHippocampal volumeCognitive dataPreclinical Alzheimer Cognitive CompositeInferior temporal tauProspective cohort studyClinically normal older adultsHarvard Aging Brain StudyPittsburgh compound B PET scansOvert cognitive impairmentAnalyzed dataNormal older adultsAging Brain StudyClinically normal adultsLongitudinal associationsAlzheimer's diseaseCohort studyMemory impairmentCognitive compositeCognitive impairmentHippocampal atrophyCognitionAssociation of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease
Prokopiou P, Engels-Domínguez N, Schultz A, Sepulcre J, Koops E, Papp K, Marshall G, Normandin M, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease. Neurology 2023, 101: e1206-e1217. PMID: 37491329, PMCID: PMC10516269, DOI: 10.1212/wnl.0000000000207646.Peer-Reviewed Original ResearchConceptsLC activityMemory declineLocus coeruleusCognitive declineEC tauHarvard Aging Brain StudyHuman neuroimaging studiesSteeper memory declineNoradrenergic brainstem nucleiLongitudinal cognitive dataFunctional MRI dataTau depositionAging Brain StudyPreclinical Alzheimer's diseaseTau progressionCortical tau depositionElevated beta-amyloidInterventions promoting resilienceMild cognitive impairmentExecutive dysfunctionExecutive functionNeuroimaging studiesTau spreadingTemporal cortexCognitive composite
2022
Correlations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals
Hong Y, Kim C, Lee J, Sepulcre J. Correlations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals. Scientific Reports 2022, 12: 14307. PMID: 35995824, PMCID: PMC9395408, DOI: 10.1038/s41598-022-18325-2.Peer-Reviewed Original ResearchConceptsApolipoprotein epsilon 4Apolipoprotein epsilon 4 alleleAlzheimer's Disease Neuroimaging InitiativeApolipoprotein epsilon 4 carriersTau burdenAmyloid depositsAPOE4 non-carriersAssociated with amyloid depositionPresence of ApoE4 alleleCross-sectional studyRegional tau burdenAssess correlationsCognitively normal participantsIncreased amyloid burdenNormal cognitive functionCognitively normal older individualsStandardized uptake value ratioEpsilon 4AD-related biomarkersAPOE4 alleleTau depositionCortical thicknessAmyloidCarrier statusAllelesAmyloid-β and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer’s disease
Guzmán-Vélez E, Diez I, Schoemaker D, Pardilla-Delgado E, Vila-Castelar C, Fox-Fuller J, Baena A, Sperling R, Johnson K, Lopera F, Sepulcre J, Quiroz Y. Amyloid-β and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2113641119. PMID: 35380901, PMCID: PMC9169643, DOI: 10.1073/pnas.2113641119.Peer-Reviewed Original ResearchConceptsDefault-mode networkFunctional connectivitySalience networkRetrospenial cortexFunctional segregationPosterior default-mode networkAmyloid-bDefault-mode network regionsHigher-order cognitive functionsEarly-onset AD dementiaTau pathologyMedial prefrontal cortexAnterior cingulate cortexDisrupting neural communicationGraph-based network analysisBrain functional architectureMedial temporal regionsFunctional networksAlzheimer's diseaseBrain functional connectivityPreclinical Alzheimer's diseasePrefrontal cortexTau burdenCingulate cortexEpisodic memory
2021
Association of cortical microstructure with amyloid-β and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults
Rodriguez-Vieitez E, Montal V, Sepulcre J, Lois C, Hanseeuw B, Vilaplana E, Schultz A, Properzi M, Scott M, Amariglio R, Papp K, Marshall G, Fortea J, Johnson K, Sperling R, Vannini P. Association of cortical microstructure with amyloid-β and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults. Molecular Psychiatry 2021, 26: 7813-7822. PMID: 34588623, PMCID: PMC8873001, DOI: 10.1038/s41380-021-01290-z.Peer-Reviewed Original ResearchConceptsCortical mean diffusivityCognitive declineOlder adultsCognitively normal older adultsHarvard Aging Brain StudyCortical microstructureInferior temporal tauProgression to mild cognitive impairmentNormal older adultsBrain structural changesAmyloid-bAging Brain StudyCompound B PETLongitudinal cognitive declineAD-vulnerable regionsHippocampal atrophy ratesCognitively normal individualsAlzheimer's diseaseMild cognitive impairmentCognitive slopesStructural MRIEntorhinal tauCognitive AssessmentCognitive impairmentLongitudinal cognition
2019
Distance disintegration delineates the brain connectivity failure of Alzheimer's disease
Costumero V, d'Oleire Uquillas F, Diez I, Andorrà M, Basaia S, Bueichekú E, Ortiz-Terán L, Belloch V, Escudero J, Ávila C, Sepulcre J. Distance disintegration delineates the brain connectivity failure of Alzheimer's disease. Neurobiology Of Aging 2019, 88: 51-60. PMID: 31941578, PMCID: PMC7085436, DOI: 10.1016/j.neurobiolaging.2019.12.005.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlzheimer DiseaseBrainCognitionCognitive DysfunctionExecutive FunctionFemaleHumansMaleNeural PathwaysConceptsAssociated with lower global cognitionCognitive impairmentAlzheimer's diseaseBrain network dysfunctionAD-related changesMild cognitive impairmentFrontoparietal networkSalience networkMode networkStrength of connectionsNetwork-based investigationsGlobal cognitionNetwork dysfunctionAD-related conditionsBrain connectivityConnectivity changesCortical regionsConnection distanceInvestigation of brain connectivityAD spectrumVoxel levelHealthy controlsDistance of connectionBrainPathways of connectivityRegional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1
Labayru G, Diez I, Sepulcre J, Fernández E, Zulaica M, Cortés J, de Munain A, Sistiaga A. Regional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1. NeuroImage Clinical 2019, 24: 102078. PMID: 31795042, PMCID: PMC6861566, DOI: 10.1016/j.nicl.2019.102078.Peer-Reviewed Original ResearchConceptsGlobal gray matterDiffusion tensor imagingCTG expansion sizeSubcortical regionsWhite matter lesionsMyotonic dystrophy type 1Fractional anisotropyStructural brain signaturesBrain atrophyAssociated with cognitive impairmentStructural cerebral changesAssociation cortical regionsDegree of muscular impairmentMicrostructural WM abnormalitiesVoxel Based MorphometryWhite matterHealthy controlsDM1 patientsRegional brain atrophyType 1Global white matterIQ estimatesNeuropsychological profileGM reductionNeuropsychological scores
2018
PET staging of amyloidosis using striatum
Hanseeuw B, Betensky R, Mormino E, Schultz A, Sepulcre J, Becker J, Jacobs H, Buckley R, LaPoint M, Vannini P, Donovan N, Chhatwal J, Marshall G, Papp K, Amariglio R, Rentz D, Sperling R, Johnson K, Initiative F, Study A. PET staging of amyloidosis using striatum. Alzheimer's & Dementia 2018, 14: 1281-1292. PMID: 29792874, PMCID: PMC6219621, DOI: 10.1016/j.jalz.2018.04.011.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlzheimer DiseaseAmyloid beta-PeptidesAmyloidosisApolipoprotein E4Brain ConcussionCognitive DysfunctionCorpus StriatumDisease ProgressionFemaleFollow-Up StudiesHumansImage Interpretation, Computer-AssistedLongitudinal StudiesMalePositron-Emission TomographyProspective StudiesSeverity of Illness IndexConceptsPositron emission tomographyHippocampal volumeCortical amyloidInvolvement of cortexPositron emission tomography dataStriatal signalingPositron emission tomography classificationAmyloid positron emission tomographyStriatumCognitive declineCortical measuresCortexPostmortem dataCognitionCortical depositsEmission tomographyIncreased predictive powerDementia progressionAdvanced amyloidosisDementia researchAlzheimerPET dataStriatalFollow-up dataPredictive power
2017
In vivo staging of regional amyloid deposition
Grothe M, Barthel H, Sepulcre J, Dyrba M, Sabri O, Teipel S, Initiative F, Initiative A, Weiner M, Aisen P, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Liu E, Green R, Montine T, Petersen R, Aisen P, Gamst A, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Jack C, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Morris J, Cairns N, Taylor-Reinwald L, Trojanowki J, Shaw L, Lee V, Korecka M, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder P, Molchan S, Kaye J, Quinn J, Lind B, Dolen S, Schneider L, Pawluczyk S, Spann B, Brewer J, Vanderswag H, Heidebrink J, Lord J, Petersen R, Johnson K, Doody R, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig L, Bell K, Morris J, Ances B, Carroll M, Leon S, Mintun M, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, deToledo-Morrell L, Shah R, Duara R, Varon D, Roberts P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon M, Glodzik L, De Santi S, Doraiswamy P, Petrella J, Coleman R, Arnold S, Karlawish J, Wolk D, Smith C, Jicha G, Hardy P, Lopez O, Oakley M, Simpson D, Porsteinsson A, Goldstein B, Martin K, Makino K, Ismail M, Brand C, Mulnard R, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Swerdlow R, Apostolova L, Lu P, Bartzokis G, Silverman D, Parfitt F, Johnson H, Farlow M, Hake A, Matthews B, Herring S, van Dyck C, Carson R, MacAvoy M, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung G, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam M, Lipowski K, Wu C, Johnson N, Sadowsky C, Martinez W, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Johnson K, Marshall G, Frey M, Yesavage J, Taylor J, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Kowall N, Killiany R, Budson A, Norbash A, Johnson P, Obisesan T, Wolday S, Bwayo S, Lerner A, Hudson L, Ogrocki P, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre D, Kataki M, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Saykin A, Santulli R, Schwartz E, Sink K, Williamson J, Garg P, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J, Longmire C, Spicer K, Finger E, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz S, Ponto L, Shim H, Smith K, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj B. In vivo staging of regional amyloid deposition. Neurology 2017, 89: 2031-2038. PMID: 29046362, PMCID: PMC5711511, DOI: 10.1212/wnl.0000000000004643.Peer-Reviewed Original ResearchConceptsAmyloid depositionAmyloid pathologyVivo stagingCognitive impairmentPrimary sensory-motor areasAmyloid stagesRegional amyloid depositionCSF Aβ42 levelsAlzheimer's disease dementiaSensory-motor areasAlzheimer's Disease Neuroimaging Initiative (ADNI) cohortNormal older individualsMedial temporal lobeMild cognitive impairmentAβ42 levelsDisease dementiaNeuropathologic observationsInitiative cohortAmyloid positivityTemporal lobeFull cohortCN individualsAssociative neocortexBrain regionsOlder individualsComplexity analysis of cortical surface detects changes in future Alzheimer's disease converters
de Miras J, Costumero V, Belloch V, Escudero J, Ávila C, Sepulcre J. Complexity analysis of cortical surface detects changes in future Alzheimer's disease converters. Human Brain Mapping 2017, 38: 5905-5918. PMID: 28856799, PMCID: PMC5745046, DOI: 10.1002/hbm.23773.Peer-Reviewed Original ResearchFunctional network integrity presages cognitive decline in preclinical Alzheimer disease
Buckley R, Schultz A, Hedden T, Papp K, Hanseeuw B, Marshall G, Sepulcre J, Smith E, Rentz D, Johnson K, Sperling R, Chhatwal J. Functional network integrity presages cognitive decline in preclinical Alzheimer disease. Neurology 2017, 89: 29-37. PMID: 28592457, PMCID: PMC5496516, DOI: 10.1212/wnl.0000000000004059.Peer-Reviewed Original ResearchConceptsPreclinical Alzheimer Cognitive CompositePreclinical Alzheimer Cognitive Composite scoreClinically normal older adultsNormal older adultsPreclinical Alzheimer's diseaseRs-fcMRICognitive declineBaseline connectivityResting-state functional connectivity MRIControl networkAD-related cognitive declineMeasures of network integrationFunctional connectivity MRIAlzheimer's diseaseNeuropsychological follow-upControl network connectivityOlder adultsFunctional network integrationCompound B PETPittsburgh compound B PETPredictor of ratingsNetwork integrationDorsal attentionCognitive compositeYears of follow-up
2015
Tau positron emission tomographic imaging in aging and early Alzheimer disease
Johnson K, Schultz A, Betensky R, Becker J, Sepulcre J, Rentz D, Mormino E, Chhatwal J, Amariglio R, Papp K, Marshall G, Albers M, Mauro S, Pepin L, Alverio J, Judge K, Philiossaint M, Shoup T, Yokell D, Dickerson B, Gomez-Isla T, Hyman B, Vasdev N, Sperling R. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Annals Of Neurology 2015, 79: 110-119. PMID: 26505746, PMCID: PMC4738026, DOI: 10.1002/ana.24546.Peer-Reviewed Original ResearchConceptsPositron emission tomographyCognitive impairmentMild cognitive impairmentClinical impairmentAssociated with clinical impairmentInferior temporal gyrusBrain tau depositionAssociation of cognitive impairmentMild AD dementiaAD dementiaAlzheimer's diseasePositron emission tomographic imagingTau positron emission tomographyTemporal gyrusMonitoring of disease progressionEmission tomographic imagingDisease-modifying therapiesSymptomatic patientsClinically normal individualsPittsburgh compound BControl subjectsDisease progressionClinically normal controlsNormal controlsImpairment
2013
Functional Connectivity in Alzheimer’s Disease: Measurement and Meaning
Johnson K, Sperling R, Sepulcre J. Functional Connectivity in Alzheimer’s Disease: Measurement and Meaning. Biological Psychiatry 2013, 74: 318-319. PMID: 23932342, DOI: 10.1016/j.biopsych.2013.07.010.Peer-Reviewed Original Research