2024
CT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease
Lizama B, Williams C, North H, Pandey K, Duong D, Di V, Mecca A, Blennow K, Zetterberg H, Levey A, Grundman M, van Dyck C, Caggiano A, Seyfried N, Hamby M. CT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 6860-6880. PMID: 39166791, PMCID: PMC11485314, DOI: 10.1002/alz.14152.Peer-Reviewed Original ResearchVolumetric magnetic resonance imagingMagnetic resonance imagingPharmacodynamic biomarkersMeta-analysisClinical developmentCerebrospinal fluidPhase 2 clinical trialResonance imagingAlzheimer's diseaseMechanism of actionClinical trialsTandem mass tag-mass spectrometryClinical cohortMild to moderate ADCandidate biomarkersCT1812CohortBiomarker signaturesBiomarkersProteomic findingsUnbiased analysisNetwork analysisAmyloid-betaSynaptic biologyBiological impactUpdated 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 imagingExamining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease
Wang G, Li Y, Xiong C, Benzinger T, Gordon B, Hassenstab J, Aschenbrenner A, McDade E, Clifford D, Libre‐Guerra J, Shi X, Mummery C, van Dyck C, Lah J, Honig L, Day G, Ringman J, Brooks W, Fox N, Suzuki K, Levin J, Jucker M, Delmar P, Bittner T, Bateman R, Team F. Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease. Alzheimer's & Dementia 2024 PMID: 38400532, DOI: 10.1002/alz.13735.Peer-Reviewed Original ResearchLatent classesPositron emission tomographyAmyloid reductionCognitive efficacyLatent class analysisAmyloid positron emission tomographyCognitive outcomesCognitive declineDominantly Inherited Alzheimer's Network Trials UnitSurrogate biomarkerBaseline characteristicsInherited Alzheimer's diseaseMultiple measuresClass analysisEmission tomographyTrials UnitAlzheimer's diseaseClinical trialsSurrogate endpointsTreatment effectsA pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligands
2023
Heterogeneity 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 predictorsLongitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease
Chen C, McCullough A, Gordon B, Joseph-Mathurin N, Flores S, McKay N, Hobbs D, Hornbeck R, Fagan A, Cruchaga C, Goate A, Perrin R, Wang G, Li Y, Shi X, Xiong C, Pontecorvo M, Klein G, Su Y, Klunk W, Jack C, Koeppe R, Snider B, Berman S, Roberson E, Brosch J, Surti G, Jiménez-Velázquez I, Galasko D, Honig L, Brooks W, Clarnette R, Wallon D, Dubois B, Pariente J, Pasquier F, Sanchez-Valle R, Shcherbinin S, Higgins I, Tunali I, Masters C, van Dyck C, Masellis M, Hsiung R, Gauthier S, Salloway S, Clifford D, Mills S, Supnet-Bell C, McDade E, Bateman R, Benzinger T. Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2669-2682. PMID: 37017737, PMCID: PMC10330155, DOI: 10.1007/s00259-023-06209-0.Peer-Reviewed Original ResearchConceptsStandardized uptake value ratioPhase 2/3 clinical trialsPositron emission tomographyAnti-Aβ monoclonal antibodyClinical trialsPlacebo armDrug effectsLongitudinal changesMonoclonal antibodiesGlobal cortical standardized uptake value ratioHead comparisonCortical standardized uptake value ratioRegional standardized uptake value ratiosAβ positron emission tomographyAmyloid-β positron emission tomographyAlzheimer's disease clinical trialsPET imagingUptake value ratioAβ PET imagingSimulated clinical trialTwo-sample t-testDrug armPittsburgh CompoundPET scansWelch two sample t-testDisease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials
Van Dyck C, O'Dell R, Mecca A. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12388. PMID: 37187779, PMCID: PMC10175943, DOI: 10.1002/trc2.12388.Peer-Reviewed Original ResearchCost Consequence Analysis of ADMET 2
Mah E, Lanctôt K, Chen Q, Shade D, Scherer R, Vieira D, Coulibaly H, Rosenberg P, Lerner A, Padala P, Brawman-Mintzer O, van Dyck C, Porsteinsson A, Mintzer J, Herrmann N. Cost Consequence Analysis of ADMET 2. American Journal Of Geriatric Psychiatry 2023, 31: s101. DOI: 10.1016/j.jagp.2022.12.147.Peer-Reviewed Original ResearchCost-consequence analysisHealth utilityPlacebo groupMethylphenidate treatmentEuroQol-five dimensions-five levelsAlzheimer's diseaseHealth statesCommon neuropsychiatric symptomsHealth utility scoresQuality of lifeBinary logistic regressionApathy treatmentBaseline demographicsDifferent time pointsPreference-based measuresMethylphenidate groupNeuropsychiatric symptomsClinical trialsEQ-5DSignificant apathyPatientsUtility scoresBetter health stateLogistic regressionMethylphenidate
2022
Heterogeneity of response to methylphenidate in apathetic patients in the ADMET 2 Trial
Lanctôt K, Perin J, Vieira D, Rosenberg P, Herrmann N, Shade D, Lerner A, Padala P, Brawman‐Mintzer O, van Dyck C, Porsteinsson A, Craft S, Levey A, Mintzer J. Heterogeneity of response to methylphenidate in apathetic patients in the ADMET 2 Trial. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.066932.Peer-Reviewed Original ResearchHeterogeneity of responseAlzheimer's diseaseAD patientsBaseline anxietyPlacebo-controlled clinical trialApathetic AD patientsDaily Living ScaleCommon neuropsychiatric symptomsLow functional capacityLower functional capabilityNPI apathy scoreLower baseline anxietyAD medicationsDifference of changesNeuropsychiatric InventoryNeuropsychiatric symptomsApathetic patientsClinical trialsMonth visitTreatment outcomesEffect differencesSignificant apathyLiving ScaleApathy scoresFunctional capacity
2021
Apathy in Dementia Methylphenidate Trial 2 (ADMET2): Results of a phase III, placebo‐controlled, double‐blind, 6‐month, multi‐center, randomized clinical trial
Mintzer J, Scherer R, Drye L, Lanctôt K, Rosenberg P, Herrmann N, Padala P, Brawman‐Mintzer O, Lerner A, Levey A, Porsteinsson A, van Dyck C. Apathy in Dementia Methylphenidate Trial 2 (ADMET2): Results of a phase III, placebo‐controlled, double‐blind, 6‐month, multi‐center, randomized clinical trial. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.051489.Peer-Reviewed Original ResearchAlzheimer's diseasePlacebo groupMethylphenidate groupClinical trialsAD Cooperative Study-Clinical Global ImpressionPhase IIITreatment of apathyClinical Global ImpressionRatings of improvementADCS-CGICAdverse eventsSecondary outcomesMonth 6Primary outcomeNeuropsychiatric symptomsSafety profileGlobal ImpressionSmall studyViable treatmentStudy participantsMean differenceMonthsMethylphenidatePrevious trialsTrials
2020
Solanezumab in‐depth outcomes
Farlow M, Bateman R, Aschenbrenner A, Benzinger T, Clifford D, Coalier K, Cruchaga C, Fagan A, Goate A, Gordon B, Hassenstab J, Jack C, Koeppe R, McDade E, Mills S, Morris J, Salloway S, Santacruz A, Snyder P, Wang G, Xiong C, Snider B, Mummery C, Surti G, Hannequin D, Wallon D, Berman S, Lah J, Jiménez‐Velazquez I, Roberson E, van Dyck C, Honig L, Sanchez‐Valle R, Brooks W, Gauthier S, Masters C, Galasko D, Brosch J, Hsiung G, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Andersen S, Holdridge K, Mintun M, Sims J, Yaari R, Team D. Solanezumab in‐depth outcomes. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.038028.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseDelayed Recall scoresAlzheimer's diseaseDisease progressionDouble-blind placebo-controlled trialLate-onset sporadic Alzheimer's diseaseTotal scoreLow-dose trialPlacebo-controlled trialAnti-amyloid therapiesOnset of symptomsPrimary cognitive outcome measureΒ-amyloid proteinInternational Shopping List TestMMSE total scoreDisease progression modelPrimary endpointSecondary outcomesSymptomatic patientsDose trialControl subjectsCSF markersClinical trialsCognitive outcome measuresEarly initiationOverview of dominantly inherited AD and top‐line DIAN‐TU results of solanezumab and gantenerumab
Bateman R, Aschenbrenner A, Benzinger T, Clifford D, Coalier K, Cruchaga C, Fagan A, Farlow M, Goate A, Gordon B, Hassenstab J, Jack C, Koeppe R, McDade E, Mills S, Morris J, Salloway S, Santacruz A, Snyder P, Wang G, Xiong C, Snider B, Mummery C, Surti G, Hannequin D, Wallon D, Berman S, Lah J, Jiménez‐Velazquez I, Roberson E, Dyck C, Honig L, Sanchez‐Valle R, Brooks W, Gauthier S, Masters C, Galasko D, Brosch J, Hsiung G, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Andersen S, Holdridge K, Mintun M, Sims J, Yaari R, Baudler M, Delmar P, Doody R, Fontoura P, Kerchner G, Team D. Overview of dominantly inherited AD and top‐line DIAN‐TU results of solanezumab and gantenerumab. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.041129.Peer-Reviewed Original ResearchDisease prevention trialsPrevention trialsAlzheimer's disease prevention trialsDifferent antigenic targetsSignificant neuronal lossKey secondary outcomesParallel-group trialAD prevention trialsAdaptive platform trialFuture clinical trialsBeta monoclonal antibodyTiming of treatmentSymptomatic ADLast patientSecondary outcomesSymptom onsetNeuronal lossTop-line resultsTreatment trialsTau-PETAntigenic targetsBrain damageClinical trialsPlatform trialsAD hypotheses
2018
Guanfacine 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
2017
Anti-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
2012
P2‐414: Baseline clinical scores and volumetric MRI parameters across subjects randomized in mild‐to‐moderate (BMS CN156‐013) and predementia (BMS CN156‐018) Alzheimer's disease clinical trials of avagacestat
Bracoud L, Coric V, van Dyck C, Andreasen N, Ross J, Brody M, Curtis C, Belaroussi B, Yu H, Kaplita S, Feldman H, Pachai C, Berman R. P2‐414: Baseline clinical scores and volumetric MRI parameters across subjects randomized in mild‐to‐moderate (BMS CN156‐013) and predementia (BMS CN156‐018) Alzheimer's disease clinical trials of avagacestat. Alzheimer's & Dementia 2012, 8: p409-p409. DOI: 10.1016/j.jalz.2012.05.2039.Peer-Reviewed Original ResearchIC‐P‐140: Baseline clinical scores and volumetric MRI parameters across subjects randomized in mild‐to‐moderate (BMS CN156‐013) and predementia (BMS CN156‐018) Alzheimer's disease clinical trials of avagacestat
Bracoud L, Coric V, van Dyck C, Andreasen N, Ross J, Brody M, Curtis C, Belaroussi B, Yu H, Kaplita S, Feldman H, Pachai C, Berman R. IC‐P‐140: Baseline clinical scores and volumetric MRI parameters across subjects randomized in mild‐to‐moderate (BMS CN156‐013) and predementia (BMS CN156‐018) Alzheimer's disease clinical trials of avagacestat. Alzheimer's & Dementia 2012, 8: p73-p74. DOI: 10.1016/j.jalz.2012.05.174.Peer-Reviewed Original ResearchSafety 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
2005
NAP: Research and Development of a Peptide Derived from Activity‐Dependent Neuroprotective Protein (ADNP)
Gozes I, Morimoto B, Tiong J, Fox A, Sutherland K, Dangoor D, Holser‐Cochav M, Vered K, Newton P, Aisen P, Matsuoka Y, van Dyck C, Thal L. NAP: Research and Development of a Peptide Derived from Activity‐Dependent Neuroprotective Protein (ADNP). CNS Neuroscience & Therapeutics 2005, 11: 353-368. PMID: 16614735, PMCID: PMC6741706, DOI: 10.1111/j.1527-3458.2005.tb00053.x.Peer-Reviewed Original ResearchConceptsActivity-dependent neuroprotective proteinIntranasal administrationClinical trialsNeuroprotective proteinPhase Ia clinical trialPhase I clinical trialApolipoprotein E deficiencyFurther clinical developmentAdverse side effectsBeta-amyloid peptideAscending dosesElectrical blockadeCardiopulmonary testSingle doseCholinergic toxicityHead injuryIntravenous formulationCognitive dysfunctionDose toxicityElderly volunteersActive doseE deficiencySide effectsAnimal modelsClinical development
2000
Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial
Mulnard R, Cotman C, Kawas C, van Dyck C, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, Grundman M, Thomas R, Thal L, Study F. Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial. JAMA 2000, 283: 1007-1015. PMID: 10697060, DOI: 10.1001/jama.283.8.1007.Peer-Reviewed Original ResearchConceptsEstrogen replacement therapyModerate Alzheimer's diseaseSecondary outcome measuresReplacement therapyAlzheimer's diseaseOutcome measuresClinical trialsPlacebo-controlled clinical trialMini-Mental State Examination scoreAlzheimer's Disease Cooperative StudyPrevention of ADClinical Dementia Rating ScaleClinical Global ImpressionPrimary outcome measureTreatment of mildSmall clinical trialsRole of estrogenState Examination scoreDementia Rating ScaleCGIC scoresEstrogen groupPlacebo groupControlled TrialsFunctional outcomeGlobal Impression
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