2015
Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial
Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, Curtis C, Soininen H, Thein S, Shiovitz T, Pilcher G, Ferris S, Colby S, Kerselaers W, Dockens R, Soares H, Kaplita S, Luo F, Pachai C, Bracoud L, Mintun M, Grill JD, Marek K, Seibyl J, Cedarbaum JM, Albright C, Feldman HH, Berman RM. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA Neurology 2015, 72: 1324-1333. PMID: 26414022, DOI: 10.1001/jamaneurol.2015.0607.Peer-Reviewed Original ResearchConceptsNonmelanoma skin cancerObservational cohortProdromal Alzheimer's diseaseProdromal ADClinical trialsPositron emission tomographyAlzheimer's diseaseDiscontinuation ratesCSF biomarkersBiomarker criteriaTreatment phasePlacebo-controlled phase 2 clinical trialSkin cancerGastrointestinal tract adverse eventsKey clinical outcome measuresSerious adverse event ratesΓ-Secretase Inhibitor AvagacestatEmission tomographyPhase 2 clinical trialPotential disease-modifying agentsBrain atrophy ratesLow discontinuation rateAdverse event ratesDisease-modifying agentsGreater brain atrophyImpact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014
Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Cedarbaum J, Donohue MC, Green RC, Harvey D, Jack CR, Jagust W, Morris JC, Petersen RC, Saykin AJ, Shaw L, Thompson PM, Toga AW, Trojanowski JQ, Initiative A. Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014. Alzheimer's & Dementia 2015, 11: 865-884. PMID: 26194320, PMCID: PMC4659407, DOI: 10.1016/j.jalz.2015.04.005.Peer-Reviewed Original ResearchConceptsAlzheimer's Disease Neuroimaging InitiativeClinical trialsDisease Neuroimaging InitiativeAlzheimer's diseaseAD clinical trialsSurrogate outcome measureAD risk factorsTraumatic brain injuryPost-traumatic stress disorderAD risk allelesMultiple sclerosisRisk factorsBrain injuryAD progressionOutcome measuresEffective treatmentParkinson's diseaseImaging ligandsMilitary populationStress disorderRisk allelesDiseaseMultiple centersBiomarkersStandardized biomarkers
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 ResearchPharmacokinetic Profile of Orally Administered Scyllo‐Inositol (Elnd005) in Plasma, Cerebrospinal Fluid and Brain, and Corresponding Effect on Amyloid‐Beta in Healthy Subjects
Liang E, Garzone P, Cedarbaum JM, Koller M, Tran T, Xu V, Ross B, Jhee SS, Ereshefsky L, Pastrak A, Abushakra S. Pharmacokinetic Profile of Orally Administered Scyllo‐Inositol (Elnd005) in Plasma, Cerebrospinal Fluid and Brain, and Corresponding Effect on Amyloid‐Beta in Healthy Subjects. Clinical Pharmacology In Drug Development 2013, 2: 186-194. PMID: 27121673, DOI: 10.1002/cpdd.14.Peer-Reviewed Original ResearchAverage trough concentrationCerebrospinal fluidAlzheimer's diseaseTrough concentrationsDay 8Magnetic resonance spectroscopy scansCSF drug levelsHealthy young subjectsPredetermined time pointsOral treatmentCSF levelsAmyloid-beta fragmentsCSF concentrationsPlasma levelsDrug levelsHealthy subjectsAmyloid betaCSF samplesPharmacokinetic profileYoung subjectsTransgenic modelBaseline levelsTime pointsWhite matter voxelsAβ fragments
2011
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology 2011, 77: 1253-1262. PMID: 21917766, PMCID: PMC3179648, DOI: 10.1212/wnl.0b013e3182309fa5.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4Dose-Response Relationship, DrugDouble-Blind MethodFemaleFollow-Up StudiesHumansInositolMagnetic Resonance ImagingMaleMental Status ScheduleMiddle AgedPeptide FragmentsPlatelet Aggregation InhibitorsTime FactorsTreatment OutcomeConceptsNeuropsychological test batteryAlzheimer's diseaseDose-ranging phase 2 studyAlzheimer's Disease Cooperative Study-ActivitiesClass II trialsClinical efficacy outcomesCSF biomarker resultsScyllo-inositol concentrationsPhase 2 studyPrimary efficacy analysisHigh-dose groupDaily Living ScaleBrain ventricular volumeCoprimary endpointsEarly discontinuationEfficacy outcomesII trialADCS-ADLDose groupEfficacy analysisAcceptable safetyAβx-42Living ScaleOptimal doseTreatment groupsNeuropsychiatric symptoms in Alzheimer's disease
Lyketsos CG, Carrillo MC, Ryan JM, Khachaturian AS, Trzepacz P, Amatniek J, Cedarbaum J, Brashear R, Miller DS. Neuropsychiatric symptoms in Alzheimer's disease. Alzheimer's & Dementia 2011, 7: 532-539. PMID: 21889116, PMCID: PMC3299979, DOI: 10.1016/j.jalz.2011.05.2410.Peer-Reviewed Original ResearchSuitability of the Clinical Dementia Rating‐Sum of Boxes as a single primary endpoint for Alzheimer's disease trials
Coley N, Andrieu S, Jaros M, Weiner M, Cedarbaum J, Vellas B. Suitability of the Clinical Dementia Rating‐Sum of Boxes as a single primary endpoint for Alzheimer's disease trials. Alzheimer's & Dementia 2011, 7: 602-610.e2. PMID: 21745761, DOI: 10.1016/j.jalz.2011.01.005.Peer-Reviewed Original ResearchConceptsClinical Dementia Rating SumCo-primary endpointsPrimary endpointSingle primary endpointCDR-SBInternal responsivenessFunctional impairmentADAS-CogDisease trialsExternal responsivenessAlzheimer's diseaseAlzheimer's Disease Assessment Scale-cognitive subscaleFloor/ceiling effectsCDR-SB changeDisease-modifying trialsModerate AD patientsDaily Living ScaleAlzheimer's disease trialsConvergent validityInternal consistencyAD trialsDisease stageAD patientsInstrumental activitiesMean changeO4‐06‐07: 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 ResearchP2‐509: Population pharmacokinetic analysis of plasma, cerebrospinal fluid and brain ELND005 in patients with mild to moderate Alzheimer's disease
Wagg J, Green M, Yan L, Liang E, Cedarbaum J, Abushakra S. P2‐509: Population pharmacokinetic analysis of plasma, cerebrospinal fluid and brain ELND005 in patients with mild to moderate Alzheimer's disease. Alzheimer's & Dementia 2011, 7: s475-s475. DOI: 10.1016/j.jalz.2011.05.1380.Peer-Reviewed Original ResearchRevision of the criteria for Alzheimer's disease: A symposium
DeKosky ST, Carrillo MC, Phelps C, Knopman D, Petersen RC, Frank R, Schenk D, Masterman D, Siemers ER, Cedarbaum JM, Gold M, Miller DS, Morimoto BH, Khachaturian AS, Mohs RC. Revision of the criteria for Alzheimer's disease: A symposium. Alzheimer's & Dementia 2011, 7: e1-e12. PMID: 21322828, DOI: 10.1016/j.jalz.2010.12.007.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseClinical diagnosisRelated Disorders Association criteriaAlzheimer's Association Research RoundtableDefinitive clinical diagnosisCurrent diagnostic criteriaPotential diagnostic biomarkersPresymptomatic Alzheimer's diseaseCurrent standardMild cognitive impairmentClinical presentationAD pathologyClinicopathologic correlationAssociation criteriaDiagnostic criteriaMild stageCognitive impairmentDiagnostic biomarkersCommunicative DisordersResearch RoundtableDiseaseBetter ascertainmentGenetics of ADCurrent criteriaDiagnosis
2010
Seeing with new eyes: Finding a path to early intervention trials in Alzheimer's disease
Cedarbaum JM, Crans G, Grundman M. Seeing with new eyes: Finding a path to early intervention trials in Alzheimer's disease. The Journal Of Nutrition, Health & Aging 2010, 14: 306-309. PMID: 20306002, DOI: 10.1007/s12603-010-0069-y.Peer-Reviewed Original ResearchConceptsMild cognitive impairmentAlzheimer's diseaseOutcome measuresClinical Dementia Rating SumClinical staging algorithmsPrimary outcome measureAD clinical trialsEarly intervention trialsComprehensive outcome measuresIdentification of MCIClinical courseIntervention trialsAD patientsClinical trialsDementia pathologyClinical characterizationCognitive impairmentEarly identificationDegenerative disordersNormal cognitionStaging algorithmDiseaseBiomarker informationBiomarker dataTrials