2024
Self‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort
Miller A, Sharp E, Wang S, Zhao Y, Mecca A, van Dyck C, O'Dell R, Initiative F. Self‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort. Alzheimer's & Dementia 2024 PMID: 39324520, DOI: 10.1002/alz.14252.Peer-Reviewed Original ResearchSelf-reported hearing lossFunctional Activities QuestionnaireHearing lossMild cognitive impairmentModifiable risk factorsMild cognitive impairment participantsFunctional declineImpairment diagnosisModified Preclinical Alzheimer Cognitive CompositeRate of functional declineRate of cognitive declinePreclinical Alzheimer Cognitive CompositeRisk factorsCognitive impairmentSignificant longitudinal associationsActivity QuestionnaireLongitudinal associationsAlzheimer's Disease Neuroimaging InitiativeLongitudinal relationshipCognitive compositeCN participantsIncreased riskCognitive declineParticipantsDiagnostic conversion
2023
Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab
Mallinckrodt C, Tian Y, Aisen P, Barkhof F, Cohen S, Dent G, Hansson O, Harrison K, Iwatsubo T, Mummery C, Muralidharan K, Nestorov I, Nisenbaum L, Rajagovindan R, von Hehn C, van Dyck C, Vellas B, Wu S, Zhu Y, Sandrock A, Chen T, Budd Haeberlein S. Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab. The Journal Of Prevention Of Alzheimer's Disease 2023, 10: 171-177. PMID: 36946443, DOI: 10.14283/jpad.2023.6.Peer-Reviewed Original ResearchConceptsHigh-dose armAmyloid-related imaging abnormalitiesPhase 3 studyBaseline characteristicsImaging abnormalitiesAlzheimer's diseaseDiscordant resultsParallel-group studyHigh-dose groupMild AD dementiaEarly Alzheimer's diseaseMild cognitive impairmentSecondary endpointsTreatment armsAD dementiaAmyloid pathologyMulticenter studyRapid progressionSignificant treatment effectSafety resultsTarget dosePatientsAducanumabCognitive impairmentNon-significant differenceLecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease
Cohen S, van Dyck C, Gee M, Doherty T, Kanekiyo M, Dhadda S, Li D, Hersch S, Irizarry M, Kramer L. Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease. The Journal Of Prevention Of Alzheimer's Disease 2023, 10: 771-777. PMID: 37874099, DOI: 10.14283/jpad.2023.123.Peer-Reviewed Original ResearchConceptsZarit Burden InterviewPhase 3 trialEarly Alzheimer's diseaseAlzheimer's diseaseQoL-ADPartner burdenMean changeDouble-blind phase 3 trialCerebrospinal fluid evidenceHumanized IgG1 monoclonal antibodyMarkers of amyloidLife-5 DimensionsHealth-related qualityPhase 3 developmentCare partner burdenLess increaseCerebral amyloid accumulationLess declineYears of ageQuality of lifePositron emission tomographyMild cognitive impairmentIgG1 monoclonal antibodyValuable patientsBurden Interview
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 ResearchConceptsMiddle temporal gyrusMild cognitive impairmentMotivation circuitsFunctional connectivityPath analysisWhole-brain regressionPCu/PCCState functional connectivityTotal scoreTemporal gyrusNeural markersCingulate cortexMemory dysfunctionRSFCHealthy controlsCognitive statusCognitive impairmentAlzheimer's diseaseApathyPrecuneusMemoryRsFCsDepressionScale total scoreCognitive subscoresLecanemab in Early Alzheimer’s Disease
van Dyck C, Swanson C, Aisen P, Bateman R, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer L, Iwatsubo T. Lecanemab in Early Alzheimer’s Disease. New England Journal Of Medicine 2022, 388: 9-21. PMID: 36449413, DOI: 10.1056/nejmoa2212948.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseasePositron emission tomographyDisease Assessment ScaleAlzheimer's diseaseAmyloid burdenAlzheimer's Disease Cooperative Study-ActivitiesAmyloid-related imaging abnormalitiesKey secondary end pointEnd pointAlzheimer's Disease Assessment ScaleClinical Dementia Rating SumHumanized IgG1 monoclonal antibodyMarkers of amyloidInfusion-related reactionsPrimary end pointSecondary end pointsCerebrospinal fluid testingPhase 3 trialBrain amyloid burdenDaily Living ScaleEvidence of amyloidCDR-SB scoresYears of ageMild cognitive impairmentIgG1 monoclonal antibodyPerformance 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 ResearchConceptsPlasma 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 sumTwo Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease
Budd Haeberlein S, Aisen P, Barkhof F, Chalkias S, Chen T, Cohen S, Dent G, Hansson O, Harrison K, von Hehn C, Iwatsubo T, Mallinckrodt C, Mummery C, Muralidharan K, Nestorov I, Nisenbaum L, Rajagovindan R, Skordos L, Tian Y, van Dyck C, Vellas B, Wu S, Zhu Y, Sandrock A. Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease. The Journal Of Prevention Of Alzheimer's Disease 2022, 9: 197-210. PMID: 35542991, DOI: 10.14283/jpad.2022.30.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseasePhase 3 studyAlzheimer's diseaseDisease dementiaAmyloid betaDisease pathophysiologyRandomized phase 3 studyClinical Dementia Rating SumCommon adverse eventsSecondary clinical endpointsPrimary outcome measureDose-dependent reductionAlzheimer's disease pathophysiologyAlzheimer's disease dementiaHuman monoclonal antibodyMild cognitive impairmentMild Alzheimer's disease dementiaPrimary endpointSecondary endpointsWeek 78Adverse eventsBiomarker substudyClinical outcomesEfficacy analysisBackgroundAlzheimer’s disease
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 ResearchConceptsMild cognitive impairmentAmnestic mild cognitive impairmentAerobic exerciseOlder adultsCognitive impairmentMass mailingElectronic health recordsClinic rostersRandomized participantsExercise trialsIntervention trialsPublic service announcementsLocal registryTrialsHealth recordsAdultsCognitive trajectoriesCommunity presentationsImpairmentMailingAgeExerciseRecruitment rates
2020
Recruitment for a multi‐site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial
LaCroix A, van Dyck C, Okonkwo O, Tam S, Fairchild J, Li C, Welsh‐Bohmer K, Shadyab A, Matthews G, Bennett D, Shadyab A, Schafer K, Morrison R, Kipperman S, Tan D, Feldman H, Cotman C, Baker L, Group E. Recruitment for a multi‐site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.044658.Peer-Reviewed Original ResearchAerobic exerciseCognitive impairmentPerson screeningExercise intervention studiesDays/weekAmnestic mild cognitive impairmentMild cognitive impairmentElectronic health recordsExercise trialsBrain healthConclusion AgeSedentary adultsFirst mailingAdults 65Wake Forest SchoolIntervention studiesClinical sitesStudy candidatesPatient rosterOlder adultsCoordinating CenterNational media campaignTrialsRecruitment challengesHealth recordsPET 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 measures
2009
123I-5-IA-85380 SPECT Imaging of Nicotinic Receptors in Alzheimer Disease and Mild Cognitive Impairment
Mitsis EM, Reech KM, Bois F, Tamagnan GD, MacAvoy MG, Seibyl JP, Staley JK, van Dyck CH. 123I-5-IA-85380 SPECT Imaging of Nicotinic Receptors in Alzheimer Disease and Mild Cognitive Impairment. Journal Of Nuclear Medicine 2009, 50: 1455-1463. PMID: 19690024, DOI: 10.2967/jnumed.109.064030.Peer-Reviewed Original ResearchConceptsAdvanced Alzheimer's diseaseMild cognitive impairmentHealthy control subjectsControl subjectsCognitive impairmentAge-matched healthy control subjectsAlzheimer's diseaseBrain regionsEffect of diagnosisNicotinic acetylcholine receptorsLate-stage phenomenonCholinergic reductionIA-85380Effect of ageUnivariate analysisNicotinic receptorsAnterior cingulateConstant infusionAcetylcholine receptorsTrail Making TestMultivariate analysisNeuropsychologic variablesDiagnostic groupsSignificant overall effectSPECT imaging