2023
Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloidAmyloidogenic ProteinsBrainCognitive DysfunctionHumansPositron-Emission TomographyPrincipal Component AnalysisConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patterns
2022
Hypothalamic Functional Connectivity and Apathy in People with Alzheimer’s Disease and Cognitively Normal Healthy Controls
Chaudhary S, Zhornitsky S, Chao H, van Dyck C, Li C. Hypothalamic Functional Connectivity and Apathy in People with Alzheimer’s Disease and Cognitively Normal Healthy Controls. Journal Of Alzheimer's Disease 2022, 90: 1615-1628. PMID: 36314209, PMCID: PMC10064487, DOI: 10.3233/jad-220708.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesApathyCognitive DysfunctionHumansMagnetic Resonance ImagingConceptsMiddle temporal gyrusMild cognitive impairmentMotivation circuitsFunctional connectivityPath analysisWhole-brain regressionPCu/PCCState functional connectivityTotal scoreTemporal gyrusNeural markersCingulate cortexMemory dysfunctionRSFCHealthy controlsCognitive statusCognitive impairmentAlzheimer's diseaseApathyPrecuneusMemoryRsFCsDepressionScale total scoreCognitive subscoresPerformance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease
Wilson E, Young C, Ramos Benitez J, Swarovski M, Feinstein I, Vandijck M, Le Guen Y, Kasireddy N, Shahid M, Corso N, Wang Q, Kennedy G, Trelle A, Lind B, Channappa D, Belnap M, Ramirez V, Skylar-Scott I, Younes K, Yutsis M, Le Bastard N, Quinn J, van Dyck C, Nairn A, Fredericks C, Tian L, Kerchner G, Montine T, Sha S, Davidzon G, Henderson V, Longo F, Greicius M, Wagner A, Wyss-Coray T, Poston K, Mormino E, Andreasson K. Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease. Alzheimer's Research & Therapy 2022, 14: 172. PMID: 36371232, PMCID: PMC9652927, DOI: 10.1186/s13195-022-01116-2.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitive DysfunctionHumansTau ProteinsConceptsPlasma p-tau181Alzheimer's Disease Research CenterP-tau181Disease Research CenterAlzheimer's diseasePositron emission tomographyAD dementiaBlood-based biomarker assaysAmyloid positron emission tomographyTreatment monitoringNovel blood-based biomarkersCSF p-tau181P-tau181 concentrationsDisease-modifying therapiesAβ42/Aβ40 ratioBlood-based biomarkersClinical AD diagnosisDetection of ADMild cognitive impairmentStudy cohortCSF biomarkersPlasma levelsAD groupPrognostic performanceCDR sumSynaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J
Mecca AP, O'Dell RS, Sharp ES, Banks ER, Bartlett HH, Zhao W, Lipior S, Diepenbrock NG, Chen M, Naganawa M, Toyonaga T, Nabulsi NB, Vander Wyk B, Arnsten AFT, Huang Y, Carson RE, van Dyck C. Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J. Alzheimer's & Dementia 2022, 18: 2527-2536. PMID: 35174954, PMCID: PMC9381645, DOI: 10.1002/alz.12582.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseBrainCognitionCognitive DysfunctionHumansPositron-Emission TomographySynapsesConceptsSynaptic densityEarly Alzheimer's diseaseAlzheimer's diseaseCognitive performanceMajor pathological correlateGray matter volumePositron emission tomography (PET) imagingEmission Tomography ImagingPET imaging studiesIndividual cognitive domainsNeuropathologic studiesSignificant positive associationSynapse lossSynaptic alterationsPathological correlatesNeuropsychological test performanceMatter volumeCognitive impairmentSignificant associationImaging studiesDiseaseTomography imagingGlobal cognitionStrongest predictorPositive association
2021
Recruitment of a multi‐site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial
Shadyab AH, LaCroix AZ, Feldman HH, van Dyck C, Okonkwo OC, Tam SP, Fairchild JK, Welsh‐Bohmer K, Matthews G, Bennett D, Shadyab AA, Schafer KA, Morrison RH, Kipperman SA, Mason J, Tan D, Thomas RG, Cotman CW, Baker LD, Group F. Recruitment of a multi‐site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial. Alzheimer's & Dementia 2021, 17: 1808-1817. PMID: 34297895, PMCID: PMC9292825, DOI: 10.1002/alz.12401.Peer-Reviewed Original ResearchMeSH KeywordsAgedAmnesiaCognitionCognitive DysfunctionExerciseFemaleHumansMalePamphletsPatient SelectionPostal ServiceConceptsMild cognitive impairmentAmnestic mild cognitive impairmentAerobic exerciseOlder adultsCognitive impairmentMass mailingElectronic health recordsClinic rostersRandomized participantsExercise trialsIntervention trialsPublic service announcementsLocal registryTrialsHealth recordsAdultsCognitive trajectoriesCommunity presentationsImpairmentMailingAgeExerciseRecruitment ratesAge‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates
Datta D, Leslie SN, Wang M, Morozov YM, Yang S, Mentone S, Zeiss C, Duque A, Rakic P, Horvath TL, van Dyck C, Nairn AC, Arnsten AFT. Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates. Alzheimer's & Dementia 2021, 17: 920-932. PMID: 33829643, PMCID: PMC8195842, DOI: 10.1002/alz.12325.Peer-Reviewed Original ResearchConceptsTau pathologyCalcium leakTau phosphorylationNeuronal firingAlzheimer's diseaseEarly tau phosphorylationPyramidal cell dendritesSporadic Alzheimer's diseasePrimary cortical neuronsPotential therapeutic targetCognitive performanceAge-related reductionMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexNon-human primatesCalcium dysregulationCell dendritesCortical neuronsCalcium-binding proteinsAD biomarkersPathology markersTherapeutic targetAnimal modelsAged monkeysPrefrontal cortex
2020
In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET
Mecca AP, Chen M, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Nabulsi NB, Vander Wyk B, Varma P, Arnsten AFT, Huang Y, Carson RE, van Dyck C. In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET. Alzheimer's & Dementia 2020, 16: 974-982. PMID: 32400950, PMCID: PMC7383876, DOI: 10.1002/alz.12097.Peer-Reviewed Original ResearchConceptsWidespread synaptic lossEarly Alzheimer's diseaseSynaptic lossAlzheimer's diseaseSynaptic vesicle glycoprotein 2AGray matter volumeMajor structural correlatePositron emission tomography (PET) imagingEmission Tomography ImagingDistribution volume ratioCerebellar reference regionNeocortical brain regionsSynaptic densityAD progressionConsistent pathologyPotential therapyMatter volumePromising biomarkerCognitive impairmentCN participantsBrain regionsDiseaseTomography imagingNormal participantsStructural correlatesPET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
2018
Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.Peer-Reviewed Original ResearchConceptsPositron emission tomographic imagingSynaptic vesicle glycoprotein 2ASynaptic densityAlzheimer's diseaseEmission tomographic imagingHigh-resolution PET scanningPET scanningCognitive impairmentDisease-modifying therapiesDisease-modifying treatmentsNormal participantsCross-sectional studyPittsburgh compound BMajor structural correlateAmnestic mild cognitive impairmentMagnetic resonance imagingMild cognitive impairmentJ PET imagingRestoration of synapsesSpecific bindingNeurologic evaluationSynaptic lossDisease stagePostmortem studiesOutcome measuresGuanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial
Barcelos NM, Van Ness PH, Wagner AF, MacAvoy MG, Mecca AP, Anderson GM, Trentalange M, Hawkins KA, Sano M, Arnsten AFT, van Dyck CH. Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial. Neurobiology Of Aging 2018, 70: 117-124. PMID: 30007160, PMCID: PMC6503670, DOI: 10.1016/j.neurobiolaging.2018.05.033.Peer-Reviewed Original ResearchConceptsDose of guanfacineQuality of lifeZ-scoreCognitive functionPrefrontal cognitive dysfunctionCommon adverse eventsPrimary outcome measureRandomized clinical trialsGlobal functionOlder participantsHealthy older participantsPrefrontal cognitive functionDry mouthAdverse eventsAgonist guanfacineClinical trialsGuanfacine treatmentCognitive dysfunctionMean changeOutcome measuresPlaceboGuanfacineOlder individualsWeeksDose