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 atrophyCognitionTau-PET abnormality as a biomarker for Alzheimer’s disease staging and early detection: a topological perspective
Ding J, Shen C, Wang Z, Yang Y, Fakhri G, Lu J, Liang D, Zheng H, Zhou Y, Sun T, Study F. Tau-PET abnormality as a biomarker for Alzheimer’s disease staging and early detection: a topological perspective. Cerebral Cortex 2023, 33: 10649-10659. PMID: 37653600, DOI: 10.1093/cercor/bhad312.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersBrainCognitive DysfunctionHumansPositron-Emission TomographyTau ProteinsConceptsStandardized uptake value ratioMild cognitive impairmentBrain regionsCognitive impairmentPositron emission tomographyMedial temporal lobeAlzheimer's diseaseVisual-related regionsTopological perspectiveTau positron emission tomographyMode networkTau PET imagingTopological featuresIndependent data cohortsTemporal lobeConnection strengthExtract topological featuresTau networksAbnormal networkProgression of Alzheimer's diseaseAbnormal protein accumulationAssociation 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 compositeMeasurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging
Guehl N, Dhaynaut M, Hanseeuw B, Moon S, Lois C, Thibault E, Fu J, Price J, Johnson K, El Fakhri G, Normandin M. Measurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging. Journal Of Nuclear Medicine 2023, 64: 968-975. PMID: 36997330, PMCID: PMC10241011, DOI: 10.2967/jnumed.122.265072.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAniline CompoundsBrainCerebrovascular CirculationCognitive DysfunctionHumansPositron-Emission TomographyConceptsTime-activity curvesCerebral perfusionMetabolite-corrected arterial input functionBrain time-activity curvesEarly phaseRegional time-activity curvesIndices of cerebral perfusionDynamic [<sup>18</sup>FBlood-brain barrierPlasma to brain tissueStatistically significant differenceArterial blood samplesForty-nine subjectsCNArterial input functionPathophysiological mechanismsPerfusion indicatorsPET imagingBlood samplesSignificant differenceSurrogate indexNoninvasive estimationAnatomical informationCompound BForty-nine
2022
Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [18F]MK-6240 PET uptake
Fu J, Lois C, Sanchez J, Becker J, Rubinstein Z, Thibault E, Salvatore A, Sari H, Farrell M, Guehl N, Normandin M, Fakhri G, Johnson K, Price J. Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [18F]MK-6240 PET uptake. Cerebrovascular And Brain Metabolism Reviews 2022, 43: 581-594. PMID: 36420769, PMCID: PMC10063833, DOI: 10.1177/0271678x221142139.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCognitive DysfunctionCross-Sectional StudiesHumansKineticsPositron-Emission TomographyConceptsPartial volume correctionLongitudinal changesReference regionStandardized uptake valueFollow-up scansExtracerebral signalsAssessment of longitudinal changesCross-sectional effect sizesUptake valuePET uptakeDistribution volumeRegional uptakeArterial samplesExtracerebral contaminationOne-yearCognitively-normalEffect sizePonsGroup differentiationVolume correctionSubject levelSubjectsLower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals
Prokopiou P, Engels-Domínguez N, Papp K, Scott M, Schultz A, Schneider C, Farrell M, Buckley R, Quiroz Y, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals. Nature Communications 2022, 13: 1571. PMID: 35322012, PMCID: PMC8943159, DOI: 10.1038/s41467-022-28986-2.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCognitive DysfunctionLocus CoeruleusPositron-Emission TomographyTau ProteinsConceptsCognitive declineLC activityLC-FCFunctional connectivityLocus coeruleusAssociated with altered neuronal activityNeuronal activityFace-name paradigmAD-related cognitive declineHuman imaging researchIn vivo neuronal activityLongitudinal cognitive dataAssociated with cognitive declineBeta-amyloid-PETIndividuals at-riskAlzheimer's diseaseCognitively unimpaired older individualsBeta-amyloidSubcortical regionsFunctional MRICognitive dataNeurofibrillary tauImaging researchHippocampusCognition
2021
Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease
Sprugnoli G, Munsch F, Cappon D, Paciorek R, Macone J, Connor A, El Fakhri G, Salvador R, Ruffini G, Donohoe K, Shafi M, Press D, Alsop D, Pascual Leone A, Santarnecchi E. Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease. Alzheimer's Research & Therapy 2021, 13: 203. PMID: 34930421, PMCID: PMC8690894, DOI: 10.1186/s13195-021-00922-4.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseCognitive DysfunctionHippocampusHumansPerfusionTranscranial Direct Current StimulationConceptsTemporal lobeMethodsIn two open-label studiesMild to moderate AD participantsPreclinical models of ADGamma bandBrain oscillatory activityModerate AD participantsBilateral temporal lobesEpisodic memoryAdministered 1 hSpectral power changesBrain areasModulates cerebral perfusionAD participantsPlacebo-controlled trialHippocampal perfusionModel of ADOpen-label studyNeural activityAssociated with alterationsNon-invasive countermeasureCognitive AssessmentCognitive impairmentCognitive protectionOscillatory activityIn vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline
Jacobs H, Becker J, Kwong K, Engels-Domínguez N, Prokopiou P, Papp K, Properzi M, Hampton O, d'Oleire Uquillas F, Sanchez J, Rentz D, El Fakhri G, Normandin M, Price J, Bennett D, Sperling R, Johnson K. In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline. Science Translational Medicine 2021, 13: eabj2511. PMID: 34550726, PMCID: PMC8641759, DOI: 10.1126/scitranslmed.abj2511.Peer-Reviewed Original ResearchConceptsLC integrityLongitudinal cognitive measuresCognitive measuresLocus coeruleusIndicators of Alzheimer's disease pathologyLocus coeruleus integrityMedial temporal lobeTangle densityRush Memory and Aging ProjectBraak stageMemory and Aging ProjectHyperphosphorylated tau aggregatesAlzheimer's diseaseB-amyloidAD-related processesMemory declineCognitive dysfunctionDisease pathologyCognitive trajectoriesTemporal lobeLC neuronsPostmortem correlationsCognitive declineEntorhinal cortexPreclinical AD
2019
Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects
Guehl N, Wooten D, Yokell D, Moon S, Dhaynaut M, Katz S, Moody K, Gharagouzloo C, Kas A, Johnson K, El Fakhri G, Normandin M. Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2099-2111. PMID: 31332496, PMCID: PMC6709592, DOI: 10.1007/s00259-019-04419-z.Peer-Reviewed Original ResearchConceptsReference tissue methodDistribution volume ratioTissue methodIn vivo quantificationPharmacokinetic modeling strategiesArterial plasma input functionMultilinear reference tissue methodsTwo-tissue compartment modelBlood:plasma ratioTissue-to-plasmaPlasma input functionPlasma concentration time courseBlood-based methodMethodsThirty-five subjectsSUV ratioBlood-based analysesData setsArterial input functionPET scansControl subjectsMild cognitive impairmentPlasma ratioRadiometabolite analysisHealthy controlsConcentration time course