2024
Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging
Diez I, Ortiz-Terán L, Ng T, Albers M, Marshall G, Orwig W, Kim C, Bueichekú E, Montal V, Olofsson J, Vannini P, El Fahkri G, Sperling R, Johnson K, Jacobs H, Sepulcre J. Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging. Nature Communications 2024, 15: 4809. PMID: 38844444, PMCID: PMC11156945, DOI: 10.1038/s41467-024-48462-3.Peer-Reviewed Original ResearchConceptsOlfactory systemMedial temporal lobe structuresCognitively normal older adultsOlfactory pathwayOdor identification deficitsNormal older adultsTemporal lobe structuresTau accumulationAlzheimer's diseaseIdentification deficitsGenetic vulnerabilityLobe structuresCortical systemsOlfactory circuitsAssociated with tau accumulationIdentification measuresCortical neurodegenerationOlder adultsPiB-PETTau propagationTau progressionPathological aggregationGenetic backgroundDiffusion MRIPredictive powerSpatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition
Bueichekú E, Diez I, Kim C, Becker J, Koops E, Kwong K, Papp K, Salat D, Bennett D, Rentz D, Sperling R, Johnson K, Sepulcre J, Jacobs H. Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition. Nature Aging 2024, 4: 625-637. PMID: 38664576, PMCID: PMC11108787, DOI: 10.1038/s43587-024-00626-y.Peer-Reviewed Original ResearchConceptsTau spreadingDisease pathologyGene expression profilesTau positron emission tomography imagingTranscriptomic informationLocus coeruleusHyperphosphorylated tauAlzheimer's disease pathologyTau accumulationBiological functionsExpression profilesTau depositionGenetic featuresCortical tauAlzheimer's diseaseLocus coeruleus integrityTauAssociated with lower cognitive performanceLower cognitive performanceTransport regulationLC integrityCognitive performanceAlzheimerAllocortical regionsSpatiotemporal patterns
2023
Association 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 atrophyCognition
2021
Network interdigitations of Tau and amyloid‐beta deposits define cognitive levels in aging
Kim C, Montal V, Diez I, Orwig W, Initiative A, Sepulcre J. Network interdigitations of Tau and amyloid‐beta deposits define cognitive levels in aging. Human Brain Mapping 2021, 42: 2990-3004. PMID: 33955621, PMCID: PMC8193537, DOI: 10.1002/hbm.25350.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAgingAmyloid beta-PeptidesBrainFemaleHumansMaleNerve NetPositron-Emission TomographyTau ProteinsConceptsCognitively normal older adultsAmyloid-betaPathological hallmarks of Alzheimer's diseaseHallmarks of Alzheimer's diseaseTau depositionPositron emission tomographyGeneral cognitive impairmentTau neurofibrillary tanglesAlzheimer's diseaseNormal older adultsOlder adultsAmyloid-beta depositionCognitive test scoresTau pathogenesisAD vulnerable areasNeurofibrillary tanglesHeteromodal areasTau accumulationCognitive changesCognitive deteriorationCognitive impairmentCognitive declinePathological hallmarkPreclinical ADCognitive levelLongitudinal predictive modeling of tau progression along the structural connectome
Yang F, Chowdhury S, Jacobs H, Sepulcre J, Wedeen V, Johnson K, Dutta J. Longitudinal predictive modeling of tau progression along the structural connectome. NeuroImage 2021, 237: 118126. PMID: 33957234, PMCID: PMC8260445, DOI: 10.1016/j.neuroimage.2021.118126.Peer-Reviewed Original ResearchConceptsHarvard Aging Brain StudyTau progressionDiffusion tensor imagingLongitudinal predictive modelsAlzheimer's Disease Neuroimaging InitiativeAlzheimer's diseaseTau PET scansPositron emission tomographyLongitudinal positron emission tomographyTau neurofibrillary tanglesAging Brain StudyTau measuresNeurofibrillary tanglesTau transmissionStructural connectivity mapsPET scansCognitive declineBrain studiesPhysiological processesTensor imagingTauStructural connectomeGoodness of model fitClosed-form solutionPrediction framework
2019
Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults
Vannini P, Uquillas F, Jacobs H, Sepulcre J, Gatchel J, Amariglio R, Hanseeuw B, Papp K, Hedden T, Rentz D, Pascual-Leone A, Johnson K, Sperling R. Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults. NeuroImage Clinical 2019, 24: 102097. PMID: 31795044, PMCID: PMC6879982, DOI: 10.1016/j.nicl.2019.102097.Peer-Reviewed Original ResearchConceptsFeeling-of-knowingEpisodic feeling-of-knowingCognitively unimpaired older adultsMeta-memoryMedial temporal lobe regionsOlder adultsFace-name pairsRegion-of-interest analysisTemporal lobe regionsAlzheimer's diseaseVoxel-wise correlationSemantic knowledge networkTemporal poleLobe regionsEntorhinal cortexNon-famousSensitive clinical indicatorMulti-tracer PETMemory efficiencySemantic informationAdultsTau pathologyAD pathophysiologyParticipantsPET dataFunctional and Pathological Correlates of Judgments of Learning in Cognitively Unimpaired Older Adults
Uquillas F, Jacobs H, Schultz A, Hanseeuw B, Buckley R, Sepulcre J, Pascual-Leone A, Donovan N, Johnson K, Sperling R, Vannini P. Functional and Pathological Correlates of Judgments of Learning in Cognitively Unimpaired Older Adults. Cerebral Cortex 2019, 30: 1974-1983. PMID: 31696223, PMCID: PMC7132950, DOI: 10.1093/cercor/bhz217.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingCognitively unimpaired older adultsMetamemory processesMemory performanceOlder adultsMidline regionVentromedial prefrontal cortexFunctional magnetic resonance imaging signalsHarvard Aging Brain StudyJudgments of learningAging Brain StudyAlzheimer's diseaseMemory successPrefrontal cortexAssociated with overestimationNeural substratesTau pathologyBilateral hippocampiBrain studiesJOLsCohort of older adultsMagnetic resonance imagingCognitionAD dementiaTau deposition
2018
Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology
Grothe M, Sepulcre J, Gonzalez-Escamilla G, Jelistratova I, Schöll M, Hansson O, Teipel S, Initiative A. Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology. Brain 2018, 141: 2755-2771. PMID: 30016411, PMCID: PMC6113636, DOI: 10.1093/brain/awy189.Peer-Reviewed Original ResearchConceptsRegional gene expression profilesGene expression profilesAlzheimer's disease pathologyExpression profilesPathophysiological mechanism of Alzheimer's diseaseDisease pathologyAlzheimer's diseaseAmyloid depositsExpression levelsMechanisms of Alzheimer's diseaseHuman brain transcriptomeGene set enrichment analysisTau kinasesAlzheimer's Disease Neuroimaging InitiativeMicroarray measurementsTau proteinMAPT expressionAllen Brain AtlasGene setsAmyloid precursorBrain transcriptomeRas-ERKNeurofibrillary degenerationRegionally selective vulnerabilityMitochondrial respiration
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 individualsHierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex
Sepulcre J, Grothe M, Sabuncu M, Chhatwal J, Schultz A, Hanseeuw B, Fakhri G, Sperling R, Johnson K. Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex. JAMA Neurology 2017, 74: 813-820. PMID: 28558094, PMCID: PMC5710537, DOI: 10.1001/jamaneurol.2017.0263.Peer-Reviewed Original ResearchConceptsHeteromodal areasTemporal lobeHarvard Aging Brain StudyHeteromodal association regionsAging Brain StudyCognitively normal participantsElderly brainsPositron emission tomographicPrimary somatomotor cortexDistribution volume ratioAlzheimer's diseaseTau depositionStandardized uptake value ratioVisual regionsNormal participantsAb depositionSomatomotor cortexTemporal areaPittsburgh compound BCarbon 11-labeled Pittsburgh Compound BBrain studiesAssociation regionsHuman brainPathological hallmarks of Alzheimer's diseaseCortical distributionFunctional 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-upThe association between tau PET and retrospective cortical thinning in clinically normal elderly
LaPoint M, Chhatwal J, Sepulcre J, Johnson K, Sperling R, Schultz A. The association between tau PET and retrospective cortical thinning in clinically normal elderly. NeuroImage 2017, 157: 612-622. PMID: 28545932, PMCID: PMC5772972, DOI: 10.1016/j.neuroimage.2017.05.049.Peer-Reviewed Original ResearchConceptsTemporal regionsCortical thinningCortical ROIsCortical thicknessRetrospective longitudinal analysisRight temporal regionAssociated with neuronal lossBaseline ageNormal cohortNeuronal lossRate of cortical thinningLeft cuneusPathologyMedial temporal regionsVolumetric ROIsReference regionAtrophyThick cross-sectionsCortical regionsBilateral parahippocampal cortexLongitudinal atrophyLongitudinal analysisLeft superior temporal sulcusCortexBrain studiesFluorodeoxyglucose metabolism associated with tau‐amyloid interaction predicts memory decline
Hanseeuw B, Betensky R, Schultz A, Papp K, Mormino E, Sepulcre J, Bark J, Cosio D, LaPoint M, Chhatwal J, Rentz D, Sperling R, Johnson K. Fluorodeoxyglucose metabolism associated with tau‐amyloid interaction predicts memory decline. Annals Of Neurology 2017, 81: 583-596. PMID: 28253546, PMCID: PMC5404378, DOI: 10.1002/ana.24910.Peer-Reviewed Original ResearchConceptsMemory declineFrontal hypometabolismHarvard Aging Brain StudyAssociated with frontal hypometabolismCourse of preclinical ADAssociated with memory lossAging Brain StudySignificant memory declinePreclinical Alzheimer's diseaseCerebral glucose metabolismAlzheimer's diseaseCingulate metabolismPosterior cingulate metabolismEntorhinal tauEntorhinal cortexPositron emission tomographyPittsburgh compound BPreclinical ADBrain studiesMemory lossImpact of amyloidOlder adultsHypometabolismAge-related tauopathyEmission tomographyTau and amyloid β proteins distinctively associate to functional network changes in the aging brain
Sepulcre J, Sabuncu M, Li Q, Fakhri G, Sperling R, Johnson K. Tau and amyloid β proteins distinctively associate to functional network changes in the aging brain. Alzheimer's & Dementia 2017, 13: 1261-1269. PMID: 28366797, PMCID: PMC5623176, DOI: 10.1016/j.jalz.2017.02.011.Peer-Reviewed Original ResearchConceptsAging brainFunctional connectivityAlzheimer's disease-related pathologyCognitively normal individualsPositron emission tomography scanHyperconnected regionsFunctional network changesMisfolded tauDisease-related pathologyBrain areasEmission tomography scanAmyloid-bFunctional reorganizationB proteinHuman brainNeuronal circuitsTauBrainNeuronal functionNegative associationAmyloidCortical patternsNetwork changesElderly subjectsPositive associationPhases of Hyperconnectivity and Hypoconnectivity in the Default Mode and Salience Networks Track with Amyloid and Tau in Clinically Normal Individuals
Schultz A, Chhatwal J, Hedden T, Mormino E, Hanseeuw B, Sepulcre J, Huijbers W, LaPoint M, Buckley R, Johnson K, Sperling R. Phases of Hyperconnectivity and Hypoconnectivity in the Default Mode and Salience Networks Track with Amyloid and Tau in Clinically Normal Individuals. Journal Of Neuroscience 2017, 37: 4323-4331. PMID: 28314821, PMCID: PMC5413178, DOI: 10.1523/jneurosci.3263-16.2017.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseFunctional connectivity MRITau neurofibrillary tanglesAssociated with <i>inTau-PETNeurofibrillary tanglesAmyloid pathologyCourse of preclinical ADTau levelsTau-PET signalTau PET tracersRegional tauTau PET imagingInferior temporalPreclinical ADMolecular pathologyTauReports of associationsAmyloid PET imagingCortical association networksInferior parietal cortexAmyloidAssociated with connectivityAssociation networksPreclinical Alzheimer's disease
2016
In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain
Sepulcre J, Schultz A, Sabuncu M, Gomez-Isla T, Chhatwal J, Becker A, Sperling R, Johnson K. In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain. Journal Of Neuroscience 2016, 36: 7364-7374. PMID: 27413148, PMCID: PMC4945661, DOI: 10.1523/jneurosci.0639-16.2016.Peer-Reviewed Original ResearchConceptsHallmarks of AD pathologyAmyloid-bAlzheimer's diseaseAD pathologyHallmarks of Alzheimer's diseaseElderly human brainPositron emission tomographyBrain tissue lossHuman brainTau depositionCortical associationMatter profileCortical mantleGrey matter intensityTauSpatial patternsLocal-to-localTau positron emission tomographyCognitively normal individualsEmission tomographyCognitive symptomsHallmarksTemporal lobeNetwork analysisAssociation areas
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
In vivo characterization of the early states of the amyloid-beta network
Sepulcre J, Sabuncu M, Becker A, Sperling R, Johnson K. In vivo characterization of the early states of the amyloid-beta network. Brain 2013, 136: 2239-2252. PMID: 23801740, PMCID: PMC3692037, DOI: 10.1093/brain/awt146.Peer-Reviewed Original ResearchConceptsAmyloid-bAlzheimer's diseasePittsburgh compound B positron emission tomography imagingPrecuneus/posterior cingulate cortexMedial temporal lobeRegional brain atrophyAlzheimer's disease pathologyAmyloid-betaOrbitofrontal cortexCingulate cortexAmygdala nucleiTemporal lobeCortical regionsAssociated with accumulationHub propertiesEmission tomography imagingNeurodegenerative diseasesBrain atrophyDisease pathologyAlzheimerHippocampusAbnormal accumulationCortexIn vivo characterizationElderly subjects
2011
The Dynamics of Cortical and Hippocampal Atrophy in Alzheimer Disease
Sabuncu M, Desikan R, Sepulcre J, Yeo B, Liu H, Schmansky N, Reuter M, Weiner M, Buckner R, Sperling R, Fischl B, Initiative F. The Dynamics of Cortical and Hippocampal Atrophy in Alzheimer Disease. JAMA Neurology 2011, 68: 1040-1048. PMID: 21825241, PMCID: PMC3248949, DOI: 10.1001/archneurol.2011.167.Peer-Reviewed Original ResearchConceptsMini-Mental State Examination scoreHippocampal volume lossMini-MentalDecreased cognitive performanceCognitive performanceExamination scoresCortical thinningCortical regionsMeasures of cognitive performanceMulticenter case-control studyBaseline hippocampal volumeRate of hippocampal volume lossStudies of neuroimagingMild cognitive impairmentCross-subject analysisAnnual rate of hippocampal volume lossAlzheimer's Disease Neuroimaging InitiativeStudy participantsDementia stagesVolume lossHippocampal volumeIndicators of ADCognitive impairmentHippocampal atrophyLongitudinal atrophyNeuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden
Drzezga A, Becker J, Van Dijk K, Sreenivasan A, Talukdar T, Sullivan C, Schultz A, Sepulcre J, Putcha D, Greve D, Johnson K, Sperling R. Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain 2011, 134: 1635-1646. PMID: 21490054, PMCID: PMC3102239, DOI: 10.1093/brain/awr066.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloidAniline CompoundsBenzothiazolesBrain MappingCerebral CortexCognition DisordersFemaleFluorodeoxyglucose F18HumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMiddle AgedOxygenPositron-Emission TomographyStatistics as TopicThiazolesConceptsWhole-brain connectivityDisruption of functional connectivityCortical hubsEarly functional consequencesMild cognitive impairmentFunctional connectivityAmyloid burdenCognitive impairmentNon-demented older individualsVoxel-based morphometry measuresAmyloid-positive patientsStructural magnetic resonanceDisruption of connectivityEmission tomographyCerebral glucose metabolismAlzheimer-type neurodegenerationAssociated with neuronal dysfunctionClinical Alzheimer's diseaseNon-demented subjectsCognitive symptomsIncreased amyloid burdenBrain regionsFunctional disconnectionNeuronal dysfunctionWhole-brain