2024
Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial)
Zeng L, Perin J, Gross A, Shade D, Lanctôt K, Lerner A, Mintzer J, Brawman‐Mintzer O, Padala P, van Dyck C, Porsteinsson A, Craft S, Levey A, Herrmann N, Rosenberg P. Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial). International Journal Of Geriatric Psychiatry 2024, 39: e6108. PMID: 38858522, PMCID: PMC11265565, DOI: 10.1002/gps.6108.Peer-Reviewed Original ResearchConceptsMethylphenidate groupTreating apathyPlacebo-controlled trial of methylphenidateTreatment of apathyAssociated with methylphenidateEffects of methylphenidateTrial of methylphenidateAlzheimer's diseaseFollow-upNo treatment group differencesAdverse effects of methylphenidateDiastolic blood pressureSymptom ChecklistAdverse eventsTreatment group differencesMonitoring weightMethylphenidate useMethylphenidate treatmentMedical comorbiditiesPlacebo groupParticipantsMethylphenidateGroup differencesPlacebo-controlled trialMonthly visitsUpdated safety results from phase 3 lecanemab study in early Alzheimer’s disease
Honig L, Sabbagh M, van Dyck C, Sperling R, Hersch S, Matta A, Giorgi L, Gee M, Kanekiyo M, Li D, Purcell D, Dhadda S, Irizarry M, Kramer L. Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 105. PMID: 38730496, PMCID: PMC11084061, DOI: 10.1186/s13195-024-01441-8.Peer-Reviewed Original ResearchConceptsOpen-label extensionInfusion-related reactionsIntracerebral hemorrhageAdverse eventsAmyloid-related imaging abnormalitiesARIA-HParallel-group studyClinical laboratory parametersMonths of treatmentMild-to-moderateMagnetic resonance imagingHomozygous participantsAPOE e4 carriersDouble-blindPlacebo-controlledLaboratory parametersStudy treatmentARIA-E.Imaging abnormalitiesOptimal patient carePhysical examinationSafety resultsClinical trialsHemosiderin depositionResonance imaging
2023
Trial of Solanezumab in Preclinical Alzheimer’s Disease
Sperling R, Donohue M, Raman R, Rafii M, Johnson K, Masters C, van Dyck C, Iwatsubo T, Marshall G, Yaari R, Mancini M, Holdridge K, Case M, Sims J, Aisen P. Trial of Solanezumab in Preclinical Alzheimer’s Disease. New England Journal Of Medicine 2023, 389: 1096-1107. PMID: 37458272, PMCID: PMC10559996, DOI: 10.1056/nejmoa2305032.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesPreclinical Alzheimer's diseasePositron emission tomographyBrain amyloid levelsPlacebo groupAmyloid levelsAlzheimer's diseaseF-florbetapir positron emission tomographyGlobal Clinical Dementia Rating (CDR) scoreMini-Mental State ExaminationPrimary end pointClinical Dementia Rating scorePhase 3 trialPreclinical Alzheimer's cognitive composite scoresDementia Rating scoreYears of ageForms of amyloidBrain positron emission tomographyImaging abnormalitiesCognitive composite scoreMean ageFamily historyMean changePersons 65State ExaminationRelationships of in vivo brain norepinephrine transporter and age, BMI, and gender
Koohsari S, Sadabad F, Pittman B, Gallezot J, Carson R, van Dyck C, Li C, Potenza M, Matuskey D. Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender. Synapse 2023, 77: e22279. PMID: 37382240, PMCID: PMC10416616, DOI: 10.1002/syn.22279.Peer-Reviewed Original ResearchConceptsBody mass indexMultilinear reference tissue model 2Gender-related differencesBrain norepinephrine transportersNorepinephrine transporterAge-related declineStructural MR scansBrain regionsReference tissue model 2Mass indexRaphe nucleusLocus coeruleusOccipital cortexBMI relationshipHealthy adultsHigh-resolution research tomographAvailable radiotracersHealthy participantsMR scansAgeAnatomic templateReference regionNegative associationNet availabilityPotential ageHeterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial
Lanctôt K, Rivet L, Tumati S, Perin J, Sankhe K, Vieira D, Mintzer J, Rosenberg P, Shade D, Lerner A, Padala P, Brawman-Mintzer O, van Dyck C, Porsteinsson A, Craft S, Levey A, Padala K, Herrmann N. Heterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial. American Journal Of Geriatric Psychiatry 2023, 31: 1077-1087. PMID: 37385898, PMCID: PMC10765607, DOI: 10.1016/j.jagp.2023.06.002.Peer-Reviewed Original ResearchConceptsDiastolic blood pressureBlood pressureClinical predictorsDisease patientsAlzheimer's Disease Cooperative Study-ActivitiesHg diastolic blood pressureOptimal diastolic blood pressureMulti-center clinical trialDaily Living ScaleYears of ageAlzheimer's disease patientsHeterogeneity of responseApathy domainApathetic patientsClinical trialsFunctional impairmentTreatment benefitSignificant apathyLiving ScaleImpaired functionBaseline anxietyCholinesterase inhibitorsMedium effect sizeMethylphenidatePotential predictors
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 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
2012
Safety and biomarker effects of solanezumab in patients with Alzheimer's disease
Farlow M, Arnold SE, van Dyck C, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Paul SM, Siemers ER. Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimer's & Dementia 2012, 8: 261-271. PMID: 22672770, DOI: 10.1016/j.jalz.2011.09.224.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedCognition DisordersDose-Response Relationship, DrugDouble-Blind MethodElectroencephalographyEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesHumansMaleMiddle AgedNeuropsychological TestsPeptide FragmentsPsychiatric Status Rating ScalesPyridinesTomography, Emission-Computed, Single-PhotonTreatment OutcomeConceptsAlzheimer's Disease Assessment Scale-cognitive portionAntibody administrationDose-dependent mannerAlzheimer's diseaseAntibody treatmentAnti-β-amyloid antibodiesPlacebo-controlled clinical trialMagnetic resonance imaging (MRI) scansCerebrospinal fluid examinationClinical laboratory valuesActive treatment periodCSF cell countResonance imaging scansModerate Alzheimer's diseaseDose-dependent increaseMagnetic resonance imagingWeekly infusionsAdverse eventsFluid examinationImaging scansClinical trialsLaboratory valuesTreatment periodAmyloid plaquesCell count
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 imagingRegional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer's disease with [18F]deuteroaltanserin and PET
Santhosh L, Estok KM, Vogel RS, Tamagnan GD, Baldwin RM, Mitsis EM, MacAvoy MG, Staley JK, van Dyck CH. Regional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer's disease with [18F]deuteroaltanserin and PET. Psychiatry Research 2009, 173: 212-217. PMID: 19682865, DOI: 10.1016/j.pscychresns.2009.03.007.Peer-Reviewed Original ResearchConceptsPositron emission tomographyAD patient samplesAlzheimer's diseaseAD patientsAnterior cingulateBehavioral symptomsBrain serotonin 2A (5-HT(2A)) receptorsPatient samplesConstant infusion paradigmSerotonin 2A receptorProbable Alzheimer's diseaseMajor behavioral symptomsBehavioral correlatesInfusion paradigmPostmortem studiesPsychotic symptomsElderly controlsMRI scansSubcortical regionsSerotonergic dysregulationEmission tomographyPatientsDiseaseInterest analysisSymptoms
2008
Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT
Mitsis EM, Cosgrove KP, Staley JK, Bois F, Frohlich EB, Tamagnan GD, Estok KM, Seibyl JP, van Dyck CH. Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT. Neurobiology Of Aging 2008, 30: 1490-1497. PMID: 18242781, PMCID: PMC3523217, DOI: 10.1016/j.neurobiolaging.2007.12.008.Peer-Reviewed Original ResearchConceptsHigh-affinity nicotineEffect of ageReceptor availabilityBrain regionsNicotinic acetylcholine receptor availabilityConstant infusion paradigmHuman postmortem studiesHuman subjectsSingle photon emissionIA-85380NAChR availabilityAge-related declineInfusion paradigmPostmortem studiesPostmortem reportsAgePhoton emissionNicotinePearson correlationCognitive agingSubjectsLinear regressionNonsmokersBolusNAChRs
2007
Striatal dopamine transporters correlate with simple reaction time in elderly subjects
van Dyck CH, Avery RA, MacAvoy MG, Marek KL, Quinlan DM, Baldwin RM, Seibyl JP, Innis RB, Arnsten AF. Striatal dopamine transporters correlate with simple reaction time in elderly subjects. Neurobiology Of Aging 2007, 29: 1237-1246. PMID: 17363113, PMCID: PMC3523216, DOI: 10.1016/j.neurobiolaging.2007.02.012.Peer-Reviewed Original ResearchConceptsStriatal DAT availabilityDAT availabilitySimple reaction timeStriatal dopamine transporter availabilityNigrostriatal dopamine systemNigrostriatal dopaminergic functionStriatal dopamine transporterMotor performanceDopamine transporter availabilityHealthy elderly individualsBrain uptakeDopaminergic functionAdvanced ageElderly subjectsContribution of ageTransporter availabilityHealthy volunteersElderly individualsDopamine systemCarbomethoxy-3betaNeuropsychological evaluationDopamine transporterMotor measuresNeurobiological substratesAge
2006
Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease
Zdanys KF, Kleiman TG, MacAvoy MG, Black BT, Rightmer TE, Grey M, Garman KS, Tampi RR, Gelernter J, van Dyck CH. Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease. Neuropsychopharmacology 2006, 32: 171-179. PMID: 16841077, DOI: 10.1038/sj.npp.1301148.Peer-Reviewed Original ResearchConceptsAD patientsPsychotic symptomsAlzheimer's diseaseBehavioral symptomsNeuropsychiatric InventoryApolipoprotein EMultiple logistic regression modelSporadic Alzheimer's diseaseGenetic risk factorsSevere-stage Alzheimer's diseaseLogistic regression modelsDifferent risk profilesDementia progressesRisk factorsIncrease riskBehavioral disturbancesPatientsDisease severitySymptomsSignificant psychosisRisk profileGreater riskApoEExploratory analysisDisease
2005
Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease
Basso M, Gelernter J, Yang J, MacAvoy MG, Varma P, Bronen RA, van Dyck CH. Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease. Neurobiology Of Aging 2005, 27: 1416-1424. PMID: 16182410, DOI: 10.1016/j.neurobiolaging.2005.08.002.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD patientsAPOE epsilon4AD groupImportant genetic risk factorApolipoprotein E epsilon4Regional brain atrophyAPOE epsilon4 alleleElderly control subjectsNormal elderly control subjectsGenetic risk factorsAmygdaloid volumesBrain atrophyControl subjectsEpsilon4 carriersRisk factorsEpsilon4 alleleHippocampal volumeEpsilon4 doseAnalysis of covarianceDisease severityPatientsEpsilon4AmygdalaAtrophy
2001
Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and [18F]deuteroaltanserin
Soares J, van Dyck C, Tan P, Zoghbi S, Garg P, Soufer R, Baldwin R, Fujita M, Staley J, Fu X, Amici L, Seibyl J, Innis R. Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and [18F]deuteroaltanserin. Psychiatry Research 2001, 106: 81-93. PMID: 11306248, DOI: 10.1016/s0925-4927(01)00071-3.Peer-Reviewed Original ResearchConceptsTest/retest reproducibilityPositron emission tomographyCortical brain areasIntra-class correlation coefficientRetest reproducibilityBrain areasBrain measuresHealthy human subjectsMean intra-class correlation coefficientOutcome measuresConstant infusionParent tracerBlood measurementsEmission tomographyNeuropsychiatric disordersPET measuresReceptorsHuman subjectsPET acquisitionMean intraEquilibrium imagingImaging methodInfusionBolusRT
2000
Equilibrium modeling of 5-ht2a receptors with [18f]deuteroaltanserin and pet: feasibility of a constant infusion paradigm
van Dyck C, Soares J, Tan P, Staley J, Baldwin R, Amici L, Fu X, Garg P, Seibyl J, Charney D, Innis R. Equilibrium modeling of 5-ht2a receptors with [18f]deuteroaltanserin and pet: feasibility of a constant infusion paradigm. Nuclear Medicine And Biology 2000, 27: 715-722. PMID: 11150702, DOI: 10.1016/s0969-8051(00)00160-8.Peer-Reviewed Original ResearchConceptsSpecific brain uptakeConstant infusion paradigmBrain uptakeInfusion paradigmConstant infusionPromising positron emission tomography (PET) ligandPositron emission tomography (PET) ligandVenous blood samplingHealthy male subjectsSerotonin 2A receptorStable radiotracerCerebellar ratioInfusion periodBlood samplingTomography ligandH postinjectionTime-activity curvesParent tracerLinear regression analysisMale subjectsPET radioligandSlow metabolismHuman subjectsBrain activityRegression analysis