2023
Blood‐based biomarkers for predicting treatment response in the Apathy in Dementia Methylphenidate Trial 2 randomized clinical trial
Tumati S, Vieira D, Bawa K, Andreazza A, Mintzer J, Scherer R, Rosenberg P, van Dyck C, Padala P, Brawman‐Mintzer O, Porsteinsson A, Lerner A, Craft S, Levey A, Burke W, Perin J, Shade D, Herrmann N, Lanctôt K. Blood‐based biomarkers for predicting treatment response in the Apathy in Dementia Methylphenidate Trial 2 randomized clinical trial. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079161.Peer-Reviewed Original ResearchLocalization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease
Datta D, Perone I, Morozov Y, Arellano J, Duque A, Rakic P, van Dyck C, Arnsten A. Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease. Cerebral Cortex 2023, 33: 11501-11516. PMID: 37874022, PMCID: PMC10724870, DOI: 10.1093/cercor/bhad382.Peer-Reviewed Original ResearchConceptsHCN1 channelsTau pathologyGlutamate synapsesEntorhinal cortexCalcium actionInternal calcium releaseEntorhinal cortex stellate cellsDorsolateral prefrontal cortexSusceptible neuronsInitial pathologySelective vulnerabilityEtiological factorsTau phosphorylationStellate cellsAlzheimer's diseaseSpecific neuronsCalcium releasePrefrontal cortexCortexSynapse strengthPathologyCalcium signalingCalbindinDiseaseNeuronsAssessment 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 impairmentDiseaseEffects of methylphenidate on neuropsychiatric symptoms in Alzheimer's disease: Evidence from the ADMET 2 study
Clark E, Perin J, Herrmann N, Brawman‐Mintzer O, Lanctôt K, Lerner A, Mintzer J, Padala P, Rosenberg P, Sami S, Shade D, van Dyck C, Porsteinsson A, Group F. Effects of methylphenidate on neuropsychiatric symptoms in Alzheimer's disease: Evidence from the ADMET 2 study. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12403. PMID: 37538343, PMCID: PMC10394740, DOI: 10.1002/trc2.12403.Peer-Reviewed Original ResearchNeuropsychiatric symptomsEffects of methylphenidateAlzheimer's diseaseSecondary analysisNeuropsychiatric Inventory scoresElation/euphoriaSymptoms of apathyIndividual neuropsychiatric symptomsPresentation of symptomsImpact of methylphenidateIndividual domain scoresAppetite/Catecholaminergic dysfunctionMonth 6Neuropsychiatric InventoryCaregiver scoresNPI domainsNew symptomsTreatment periodDomain scoresMeaningful improvementsMethylphenidateSymptomsPlaceboDiseaseCost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).
Lanctôt K, Chen C, Mah E, Kiss A, Li A, Shade D, Scherer R, Vieira D, Coulibaly H, Rosenberg P, Lerner A, Padala P, Brawman-Mintzer O, van Dyck C, Porsteinsson A, Craft S, Levey A, Burke W, Mintzer J, Herrmann N. Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2). International Psychogeriatrics 2023, 35: 664-672. PMID: 37066690, PMCID: PMC10579450, DOI: 10.1017/s1041610223000327.Peer-Reviewed Original ResearchConceptsCost-consequence analysisTreatment of apathyFive-level questionnaireTrial 2Quality of lifeBinary logistic regressionPlacebo groupPlacebo treatmentMethylphenidate treatmentSignificant apathyHealth utilityResource utilization costsAlzheimer's diseaseLogistic regressionMethylphenidateTime interactionLevel questionnaireHealthcare systemCost predictorsMeasures analysisPatientsTreatmentDiseaseMonthsUtilization costs
2022
Synaptic 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
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 correlatesNeurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate
van Dyck CH, Arnsten AFT, Padala PR, Brawman-Mintzer O, Lerner AJ, Porsteinsson AP, Scherer RW, Levey AI, Herrmann N, Jamil N, Mintzer JE, Lanctôt KL, Rosenberg PB. Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate. American Journal Of Geriatric Psychiatry 2020, 29: 51-62. PMID: 32461027, PMCID: PMC7641967, DOI: 10.1016/j.jagp.2020.04.026.Peer-Reviewed Original ResearchConceptsTreatment of apathyAlzheimer's diseaseCortical-basal ganglia circuitsPrefrontal cortexMotivated behaviorPublic health burdenSymptoms of apathyCatecholaminergic treatmentNeurobiologic rationaleNeuropsychiatric symptomsDopamine actionGanglia circuitsHealth burdenThalamocortical circuitsCognitive symptomsMethylphenidate actionsCatecholamine actionNeuronal circuitsSymptomsDiseaseApathetic behaviorTreatmentInitial trialMethylphenidateAD results
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaquesAnti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise
van Dyck CH. Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise. Biological Psychiatry 2017, 83: 311-319. PMID: 28967385, PMCID: PMC5767539, DOI: 10.1016/j.biopsych.2017.08.010.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAmyloid-related imaging abnormalitiesPutative disease-modifying treatmentsMonoclonal antibodiesOngoing prevention trialsDisease-modifying treatmentsPresymptomatic Alzheimer's diseaseImaging abnormalitiesPrevention trialsClinical efficacyPassive immunizationClinical trialsTherapeutic approachesDisease processPreclinical stageAβ-MAbNew trialsDiseaseAdditional studiesTrialsBest treatmentMAbsTreatmentAntibodiesConformation of Aβ[O1–01–06]: MEASURING APATHY IN ALZHEIMER'S DISEASE IN THE APATHY IN DEMENTIA METHYLPHENIDATE TRIAL 2 (ADMET 2): A COMPARISON OF INSTRUMENTS
Lanctot K, Scherer R, Li A, Rosenberg P, Herrmann N, Lerner A, Padala P, Brawman‐Mintzer O, van Dyck C, Porsteinsson A, Craft S, Levey A, Burke W, Mintzer J. [O1–01–06]: MEASURING APATHY IN ALZHEIMER'S DISEASE IN THE APATHY IN DEMENTIA METHYLPHENIDATE TRIAL 2 (ADMET 2): A COMPARISON OF INSTRUMENTS. Alzheimer's & Dementia 2017, 13: p184-p184. DOI: 10.1016/j.jalz.2017.07.038.Peer-Reviewed Original Research
2015
Resveratrol is safe and well-tolerated in individuals with mild-moderate dementia due to Alzheimer’s disease. (S33.009)
Turner R, Thomas R, Craft S, van Dyck C, Mintzer J, Reynolds B, Brewer J, Rissman R, Raman R, Aisen P. Resveratrol is safe and well-tolerated in individuals with mild-moderate dementia due to Alzheimer’s disease. (S33.009). Neurology 2015, 84 DOI: 10.1212/wnl.84.14_supplement.s33.009.Peer-Reviewed Original Research
2013
P1–343: A phase II study of the gamma‐secretase inhibitor avagacestat (BMS‐708163) in predementia Alzheimer's disease
Coric V, Salloway S, van Dyck C, Kerselaers W, Kaplita S, Curtis C, Ross J, Richter R, Andreasen N, Brody M, Sharma S, Cedarbaum J, Berman R. P1–343: A phase II study of the gamma‐secretase inhibitor avagacestat (BMS‐708163) in predementia Alzheimer's disease. Alzheimer's & Dementia 2013, 9: p283-p283. DOI: 10.1016/j.jalz.2013.05.569.Peer-Reviewed Original Research
2012
IC‐O1‐03: Amyloid burden and neuropsychological performance in presymptomatic first‐degree relatives at varying APOE‐ɛ4 risk for Alzheimer's disease
van Dyck C, Barcelos N, Brück A, Planeta‐Wilson B, Gelernter J, Carson R. IC‐O1‐03: Amyloid burden and neuropsychological performance in presymptomatic first‐degree relatives at varying APOE‐ɛ4 risk for Alzheimer's disease. Alzheimer's & Dementia 2012, 8: p5-p5. DOI: 10.1016/j.jalz.2012.05.018.Peer-Reviewed Original Research
2011
O4‐06‐07: Imaging and cerebrospinal fluid biomarker results of a phase II dose‐ranging study of ELND005 (Scyllo‐inositol) in mild‐to‐moderate Alzheimer's disease
Porsteinsson A, Sperling R, Salloway S, Keren R, van Dyck C, Tariot P, Arnold D, Crans G, Hernandez R, Liang E, Bairu M, Cedarbaum J, Pastrak A, Abushakra S. O4‐06‐07: Imaging and cerebrospinal fluid biomarker results of a phase II dose‐ranging study of ELND005 (Scyllo‐inositol) in mild‐to‐moderate Alzheimer's disease. Alzheimer's & Dementia 2011, 7: s695-s695. DOI: 10.1016/j.jalz.2011.05.2010.Peer-Reviewed Original ResearchP2‐499: Safety and efficacy results of a phase II randomized, placebo‐controlled, dose‐ranging study of elnd005 (scyllo‐inositol) in mild‐to‐moderate Alzheimer's disease
Salloway S, Porsteinsson A, Sperling R, Keren R, van Dyck C, Tariot P, Gilman S, Crans G, Hernandez R, Quinn G, Bairu M, Cedarbaum J, Pastrak A, Abushakra S. P2‐499: Safety and efficacy results of a phase II randomized, placebo‐controlled, dose‐ranging study of elnd005 (scyllo‐inositol) in mild‐to‐moderate Alzheimer's disease. Alzheimer's & Dementia 2011, 7: s472-s472. DOI: 10.1016/j.jalz.2011.05.1371.Peer-Reviewed Original ResearchO4‐06‐08: Safety and tolerability of BMS‐708163 in a phase II study in mild‐to‐moderate Alzheimer's disease
Salloway S, Coric V, Brody M, Andreasen N, van Dyck C, Soininen H, Thein S, Shiovitz T, Kumar S, Pilcher G, Colby S, Rollin L, Feldman H, Berman R. O4‐06‐08: Safety and tolerability of BMS‐708163 in a phase II study in mild‐to‐moderate Alzheimer's disease. Alzheimer's & Dementia 2011, 7: s695-s696. DOI: 10.1016/j.jalz.2011.05.2011.Peer-Reviewed Original ResearchIC‐P‐106: Amyloid‐ß burden and neuropsychological test performance in cognitively normal first‐degree relatives at varying genetic risk for Alzheimer's disease
van Dyck C, Brück A, Barcelos N, Planeta‐Wilson B, Benincasa A, MacAvoy M, Ding Y, Gelernter J, Carson R. IC‐P‐106: Amyloid‐ß burden and neuropsychological test performance in cognitively normal first‐degree relatives at varying genetic risk for Alzheimer's disease. Alzheimer's & Dementia 2011, 7: s51-s52. DOI: 10.1016/j.jalz.2011.05.071.Peer-Reviewed Original ResearchP1‐387: Amyloid‐ß burden and neuropsychological test performance in cognitively normal first‐degree relatives at varying genetic risk for Alzheimer's disease
van Dyck C, Brück A, Barcelos N, Planeta‐Wilson B, Benincasa A, MacAvoy M, Ding Y, Gelernter J, Carson R. P1‐387: Amyloid‐ß burden and neuropsychological test performance in cognitively normal first‐degree relatives at varying genetic risk for Alzheimer's disease. Alzheimer's & Dementia 2011, 7: s236-s236. DOI: 10.1016/j.jalz.2011.05.668.Peer-Reviewed Original Research
2009
Regional 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