2023
Association 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
Lower novelty‐related locus coeruleus function is associated with entorhinal tau‐mediated memory decline in older individuals.
Prokopiou P, Engels N, Schneider C, Schultz A, Sepulcre J, Riphagen J, Koops E, Papp K, Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Lower novelty‐related locus coeruleus function is associated with entorhinal tau‐mediated memory decline in older individuals. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.067706.Peer-Reviewed Original ResearchMemory declineLC activityLocus coeruleusEC tauEntorhinal cortexLC phasic activationAssociated with memory declineFace-name pairsMediation effectHarvard Aging Brain StudySteeper memory declineExposure to noveltyAssociated with tau depositionInferior temporal lobeSpatial patterns of tauAging Brain StudyPreclinical Alzheimer's diseaseCortical tau depositionTau depositionFusiform cortexMemory testInsular cortexMixed-effects analysisMediation analysisInferior temporalAmyloid-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
Comparing PET and MRI Biomarkers Predicting Cognitive Decline in Preclinical Alzheimer Disease
Mayblyum D, Becker J, Jacobs H, Buckley R, Schultz A, Sepulcre J, Sanchez J, Rubinstein Z, Katz S, Moody K, Vannini P, Papp K, Rentz D, Price J, Sperling R, Johnson K, Hanseeuw B. Comparing PET and MRI Biomarkers Predicting Cognitive Decline in Preclinical Alzheimer Disease. Neurology 2021, 96: e2933-e2943. PMID: 33952655, PMCID: PMC8253562, DOI: 10.1212/wnl.0000000000012108.Peer-Reviewed Original ResearchPreclinical Alzheimer's diseaseCognitive declineHarvard Aging Brain StudyPreclinical Alzheimer Cognitive CompositePrevention trialsAlzheimer's diseaseAging Brain StudyClinically normal adultsPittsburgh compound B (PiB)-PETProspective cohort studyClass II evidenceCompound B (PiB)-PETCognitive compositeIsthmus cingulateIncrease of statistical powerStructural MRICognitive evaluationBackward stepwise regressionEntorhinal cortexHigher amyloidFDG-PETBrain studiesLinear mixed-effects modelsFollow-upCohort study
2020
The relationship between cortical microstructural changes and in vivo amyloid‐β and tau in aging and preclinical Alzheimer's disease
Rodriguez‐Vieitez E, Montal V, Sepulcre J, Lois C, Hanseeuw B, Vilaplana E, Schultz A, Properzi M, Scott M, Fortea J, Johnson K, Sperling R, Vannini P. The relationship between cortical microstructural changes and in vivo amyloid‐β and tau in aging and preclinical Alzheimer's disease. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.041626.Peer-Reviewed Original ResearchCortical mean diffusivityC-PiB PETTemporo-parietal brain regionsHarvard Aging Brain StudyAmyloid-bAlzheimer's diseaseMean diffusivityPreclinical stage of Alzheimer's diseaseAging Brain StudyGray matterPreclinical Alzheimer's diseaseStages of Alzheimer's diseaseCerebellar gray matterBrain regionsRegions-of-interestTemporal regionsSurface-based approachEntorhinal cortexBrain studiesGlial activationBrain microstructural propertiesLongitudinal studyCortical MDNon-linear trajectoriesCortical microstructure
2019
Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease
Hanseeuw B, Betensky R, Jacobs H, Schultz A, Sepulcre J, Becker J, Cosio D, Farrell M, Quiroz Y, Mormino E, Buckley R, Papp K, Amariglio R, Dewachter I, Ivanoiu A, Huijbers W, Hedden T, Marshall G, Chhatwal J, Rentz D, Sperling R, Johnson K. Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease. JAMA Neurology 2019, 76: 915-924. PMID: 31157827, PMCID: PMC6547132, DOI: 10.1001/jamaneurol.2019.1424.Peer-Reviewed Original ResearchMild cognitive impairmentOlder adultsChoice of outcome measuresPreclinical Alzheimer Cognitive CompositeCognitive impairmentAssociated with cognitive changesProspective cohort studyClinically normal participantsCognitive changesAssociated with subsequent changesMeasure cognitive changeHarvard Aging Brain StudyMeasured 7 yearsPreclinical Alzheimer's diseaseAging Brain StudyPittsburgh compound B PETAlzheimer's diseaseNormal older adultsPrevention trialsOutcome measuresSerial mediation modelCohort studyInclusion criteriaCompound B PETCognitive composite
2018
Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals
Jacobs H, Hedden T, Schultz A, Sepulcre J, Perea R, Amariglio R, Papp K, Rentz D, Sperling R, Johnson K. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nature Neuroscience 2018, 21: 424-431. PMID: 29403032, PMCID: PMC5857215, DOI: 10.1038/s41593-018-0070-z.Peer-Reviewed Original ResearchConceptsPosterior cingulate cortexMemory declineCingulate cortexHippocampal volumeTau accumulationAssociated with increased mean diffusivityCognitively healthy older individualsBaseline hippocampal volumeAmyloid-positive individualsWhite matter connectivityAmyloid-negative individualsPreclinical Alzheimer's diseaseAmyloid pathologyAnimal models of Alzheimer's diseaseHealthy older individualsTau pathology propagationModel of Alzheimer's diseaseAlzheimer's diseaseTau positron emission tomographyMemory performanceNeural vulnerabilityCingulum bundleOlder individualsPositron emission tomographyMean diffusivity
2017
Functional 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-upFluorodeoxyglucose 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 tomographyPhases 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