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, 20: 7847-7858. PMID: 39324520, PMCID: PMC11567835, 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 conversionSynaptic density patterns in early Alzheimer’s disease assessed by independent component analysis
Fang X, Raval N, O’Dell R, Naganawa M, Mecca A, Chen M, van Dyck C, Carson R. Synaptic density patterns in early Alzheimer’s disease assessed by independent component analysis. Brain Communications 2024, 6: fcae107. PMID: 38601916, PMCID: PMC11004947, DOI: 10.1093/braincomms/fcae107.Peer-Reviewed Original ResearchMedial temporal brain regionsAlzheimer's diseaseTemporal brain regionsCognitive deficitsBrain regionsCognitive impairmentPostmortem studiesBinds to SV2ASynaptic densityReduction of synaptic densityIndependent component analysisSynaptic lossAlzheimerDeficitsImpairmentBrainNeocortexComponent analysisPrimary pathologySV2A
2023
Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET
Silva-Rudberg J, Salardini E, O'Dell R, Chen M, Ra J, Georgelos J, Morehouse M, Melino K, Varma P, Toyonaga T, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET. American Journal Of Geriatric Psychiatry 2023, 32: 17-28. PMID: 37673749, PMCID: PMC10840732, DOI: 10.1016/j.jagp.2023.08.002.Peer-Reviewed Original ResearchSynaptic densityAlzheimer's diseaseMean diffusivitySynaptic lossGray matter microstructureGray matter mean diffusivityDisease pathologyHippocampal synaptic densityMajor pathological correlateSetting of ADAD-related neuropathologySynaptic vesicle glycoprotein 2AHippocampal mean diffusivityAlzheimer's disease pathologyAmyloid-positive participantsMatter mean diffusivityPositron emission tomography (PET) imagingEmission Tomography ImagingGray matter structuresPathological correlatesPositive participantsInverse associationAD groupCognitive impairmentDiseasePrincipal 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 ResearchConceptsCognitive 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 patternsCorrelation between changes in apathy and global cognition in apathetic associated with Alzheimer's disease: analysis of the Apathy Dementia Methylphenidate 2 (ADMET 2) clinical trial
Lanctôt K, Sankhe K, Perin J, Herrmann N, Brawman-Mintzer O, Lerner A, Mintzer J, Padala P, Rosenberg P, Shade D, van Dyck C, Porsteinsson A. Correlation between changes in apathy and global cognition in apathetic associated with Alzheimer's disease: analysis of the Apathy Dementia Methylphenidate 2 (ADMET 2) clinical trial. American Journal Of Geriatric Psychiatry 2023, 31: s100-s101. DOI: 10.1016/j.jagp.2022.12.146.Peer-Reviewed Original ResearchDigit Span BackwardMini-Mental Status ExaminationSelective attentionGlobal cognitionApathy scoresGreater cognitive declineExecutive functionDigit spanCognitive testsCognitionMethylphenidate groupApathy symptomsCognitive declineSignificant apathyMethylphenidateCognitive impairmentStatus ExaminationApathy subscaleMemoryChange scoresApathyDisease dementiaAlzheimer's disease dementiaParticipantsAttentionInvestigating 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 difference
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 subscoresSynaptic 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 ResearchConceptsSynaptic 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 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 recordsIn 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 correlates
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
1992
Peptide T Treatment of Cognitive Impairment in HIV‐Positive Intravenous Drug Users
Rosen M, Bridge T, O'Malley S, Pearsall H, Martini B, O'Connor P, Brett‐Smith H, Thomas H, Van Dyck C, Woods S, Kosten T. Peptide T Treatment of Cognitive Impairment in HIV‐Positive Intravenous Drug Users. American Journal On Addictions 1992, 1: 332-338. DOI: 10.1111/j.1521-0391.1992.tb00359.x.Peer-Reviewed Original ResearchHIV-positive intravenous drug usersDouble-blind crossover studyPeptide T treatmentHIV-positive patientsPeptide TOpen clinical trialIntravenous drug usersVasoactive intestinal peptideAIDS dementiaCrossover studyNeuropsychological improvementAZT treatmentIntestinal peptideClinical trialsDrug usersCognitive impairmentPatientsNeuropsychological functionCognitive functionT treatmentPlaceboThree timesWeeksPotential utilityTreatment