2025
Prognostic value of plasma biomarkers for informing clinical trial design in mild-to-moderate Alzheimer’s disease
Qiu Y, Jacobs D, Messer K, Salmon D, Wellington C, Stukas S, Revta C, Brewer J, Léger G, Askew B, Donahue L, Kaplita S, Coric V, Qureshi I, Feldman H. Prognostic value of plasma biomarkers for informing clinical trial design in mild-to-moderate Alzheimer’s disease. Alzheimer's Research & Therapy 2025, 17: 97. PMID: 40317057, PMCID: PMC12046789, DOI: 10.1186/s13195-025-01745-3.Peer-Reviewed Original ResearchConceptsMild to moderate ADADAS-cog11CDR-SBBaseline plasma NfLAlzheimer's diseasePlasma biomarkersMild-to-moderate Alzheimer's diseasePrognostic valueClinical trialsBaseline NfLPlasma NfLPlacebo-controlled trialCortical volumeConcentrations of plasma biomarkersMethodsPost hoc analysisDesign of clinical trialsClinical outcome dataIncreased ventricular volumeTrial participantsVolumetric MRIBaseline concentrationsEarly disease stagesClinical trial designTrial entry criteriaAD trials
2024
Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease
Grill J, Tam S, Thai G, Vides B, Pierce A, Green K, Gillen D, Teng E, Kremen S, Beigi M, Rissman R, Léger G, Balasubramanian A, Revta C, Morrison R, Jennings R, Pa J, Zhang J, Jin S, Messer K, Feldman H. Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease. Neurology 2024, 104: e210152. PMID: 39671543, PMCID: PMC11655133, DOI: 10.1212/wnl.0000000000210152.Peer-Reviewed Original ResearchConceptsTau phosphorylationP-tau<sub>181</sub>Histone deacetylasesCDR-SBAlzheimer's diseaseCSF p-tauPrimary outcomeP-tauDiagnosis of mild cognitive impairmentAlzheimer's Disease Assessment ScaleAlzheimer's Disease Cooperative Study-ActivitiesClass III histone deacetylasePrespecified secondary outcomesCellular oxidation-reduction reactionsDisease Assessment ScaleLevels of tauAD biomarkersHolm-Bonferroni procedureMild cognitive impairmentControl type I errorThreonine 231Histone deacetylase inhibitionAcademic clinical centersAssessment ScaleAdverse events
2023
Number of completed exercise sessions is associated with slower brain atrophy in MCI over 12 months in the EXERT trial
Digma L, Aslanyan V, Brewer J, Bevins E, Katula J, Chmelo E, Hodge H, LaCroix A, Shadyab A, Jacobs D, Salmon D, Feldman H, Pa J, Baker L. Number of completed exercise sessions is associated with slower brain atrophy in MCI over 12 months in the EXERT trial. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079285.Peer-Reviewed Original ResearchSupervised exercise sessionsBrain atrophyExercise sessionsAlzheimer's Disease Cooperative StudyLess brain atrophySupervised exercise interventionLower dementia riskLate-life exerciseAmount of exerciseInferior lateral ventricleExercise armExercise interventionDementia riskBaseline ageCDR-SBAerobic trainingLateral ventricleHigh adherenceIntervention adherenceNumber of sessionsVentricular expansionExercise typePlasma Aβ42/40Amnestic MCICognitive declineA Phase 2a proof‐of‐concept double‐blind, randomized, placebo‐controlled trial of nicotinamide in early Alzheimer’s disease
Grill J, Tam S, Thai G, Pierce A, Green K, Gillen D, Teng E, Kremen S, Beigi M, Rissman R, Leger G, Zhang J, Jin S, Messer K, Feldman H. A Phase 2a proof‐of‐concept double‐blind, randomized, placebo‐controlled trial of nicotinamide in early Alzheimer’s disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.077979.Peer-Reviewed Original ResearchPhase 2a proofP-Tau 181Placebo armTotal tauCDR-SBEarly ADAmyloid beta 40Placebo-controlled trialCerebrospinal fluid levelsEarly Alzheimer's diseaseAlzheimer's disease biomarkersDisease biomarkersPhosphorylation of tauClass III histoneSecondary outcomesAdverse eventsClinical characteristicsPrimary outcomeADCS-ADLStudy armsTreatment initiationCSF biomarkersADAS-Cog13Biomarker outcomesMean changePrognostic value of plasma biomarkers in a clinical trial of mild‐to‐moderate Alzheimer’s Disease
Qiu Y, Messer K, Jacobs D, Salmon D, Kaplita S, Wellington C, Stukas S, Askew B, Brewer J, Brody M, Donahue L, Drake J, Grossman K, Hendrix S, Jicha G, Leger G, Porsteinsson A, Shadyab A, Taylor C, Thomas R, van Dyck C, Zhang J, Coric V, Qureshi I, Feldman H, Group A. Prognostic value of plasma biomarkers in a clinical trial of mild‐to‐moderate Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.076047.Peer-Reviewed Original ResearchModerate Alzheimer's diseaseAlzheimer's Disease Cooperative StudyPlasma NfLPlasma biomarkersCDR-SBADAS-cog11Baseline NfLAlzheimer's diseaseMRI outcomesClinical trialsTrial designBaseline biomarker measurementsBaseline plasma biomarkersPlacebo-controlled RCTsClinical trial designOnly significant associationGlobal functionClinical declineClinical outcomesP-tauTotal tauTreatment armsPrognostic valueSignificant treatment effectBiomarker changesEfficacy assessment of an active tau immunotherapy in Alzheimer’s disease patients with amyloid and tau pathology: a post hoc analysis of the “ADAMANT” randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial
Cullen N, Novak P, Tosun D, Kovacech B, Hanes J, Kontsekova E, Fresser M, Ropele S, Feldman H, Schmidt R, Winblad B, Zilka N. Efficacy assessment of an active tau immunotherapy in Alzheimer’s disease patients with amyloid and tau pathology: a post hoc analysis of the “ADAMANT” randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial. EBioMedicine 2023, 99: 104923. PMID: 38101301, PMCID: PMC10733085, DOI: 10.1016/j.ebiom.2023.104923.Peer-Reviewed Original ResearchConceptsTau pathologyPathological tau proteinsAlzheimer's diseaseDouble-blindPlacebo-ControlledCDR-SBTau immunotherapyTau proteinPhase 2 clinical trialAnti-tauPost hoc subgroup analysisAD-related declineDisease patientsSlowing of declineAlzheimer's disease patientsAntibody-dependent mannerAADvac1Post Hoc AnalysisActive immunotherapyTauFull analysisParallel-groupSubgroup analysisBaseline MRIEfficacy assessment
2020
Gantenerumab in‐depth outcomes
Salloway S, 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, 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, Baudler M, Delmar P, Doody R, Fontoura P, Kerchner G, Team D. Gantenerumab in‐depth outcomes. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.038049.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseAlzheimer's diseaseCognitive endpointsCDR-SBAmyloid PETBiomarker outcomesMutation carriersSecondary clinical outcomesSecondary efficacy endpointsAutosomal dominant Alzheimer's diseaseClinical trial programClinical Alzheimer's diseaseBeta monoclonal antibodySymptomatic Alzheimer's diseaseAnti-amyloid antibodiesCognitive compositeSymptomatic mutation carriersEfficacy endpointPlacebo groupPrimary outcomeClinical outcomesInitial doseFluid biomarkersTau-PETAmyloid reductionDepression predicts cognitive and functional decline one month after coronary artery bypass graft surgery (Neuropsychiatric Outcomes After Heart Surgery study)
Oldham MA, Lin I, Hawkins KA, Li F, Yuh DD, Lee HB. Depression predicts cognitive and functional decline one month after coronary artery bypass graft surgery (Neuropsychiatric Outcomes After Heart Surgery study). International Journal Of Geriatric Psychiatry 2020, 36: 452-460. PMID: 33022808, PMCID: PMC9326959, DOI: 10.1002/gps.5443.Peer-Reviewed Original ResearchConceptsCoronary artery bypass graft surgeryArtery bypass graft surgeryBypass graft surgeryCABG surgeryGraft surgeryCDR-SBProspective observational cohort studyOlder ageOne monthHamilton Depression Rating ScaleClinical Dementia Rating SumHeart Surgery studyObservational cohort studyDepression Rating ScaleSemi-structured clinical interviewTotal study sampleHopkins Verbal Learning TestPostoperative deliriumPreoperative depressionWord Fluency TestCohort studyVerbal Learning TestNeuropsychiatric outcomesTertiary careFunctional outcome
2017
Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline
Risacher S, Anderson W, Charil A, Castelluccio P, Shcherbinin S, Saykin A, Schwarz A, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Morris J, Shaw L, Khachaturian Z, Sorensen G, Carrillo M, Kuller L, Raichle M, Paul S, Davies P, Fillit H, Hefti F, Holtzman D, Mesulam M, Potter W, Snyder P, Schwartz A, Montine T, Petersen R, Aisen P, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Jiminez G, Balasubramanian A, Mason J, Sim I, Beckett L, Harvey D, Donohue M, Jack C, Bernstein M, Fox N, Thompson P, Schuff N, DeCArli C, Borowski B, Gunter J, Senjem M, Vemuri P, Jones D, Kantarci K, Ward C, Jagust W, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Landau S, Morris J, Cairns N, Householder E, Taylor-Reinwald L, Shaw L, Trojanowki J, Lee V, Korecka M, Figurski M, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Potkin S, Shen L, Faber K, Kim S, Nho K, Thal L, National N, Albert M, Frank R, Hsiao J, Kaye J, Quinn J, Silbert L, Lind B, Carter R, Dolen S, Schneider L, Pawluczyk S, Beccera M, Teodoro L, Spann B, Brewer J, Vanderswag H, Fleisher A, Heidebrink J, Lord J, Petersen R, Mason S, Albers C, Knopman D, Johnson K, Doody R, Villanueva-Meyer J, Chowdhury M, Rountree S, Dang M, Stern Y, Honig L, Bell K, Ances B, Morris J, Carroll M, Creech M, Franklin E, Mintun M, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geldmacher D, Brockington J, Roberson E, Love M, Grossman H, Mitsis E, Shah R, deToledo-Morrell L, Duara R, Varon D, Greig M, Roberts P, Albert M, Onyike C, D’Agostino D, Kielb S, Galvin J, Cerbone B, Michel C, Pogorelec D, Rusinek H, de Leon M, Glodzik L, De Santi S, Doraiswamy M, Petrella J, Borges-Neto S, Wong T, Coleman E, Arnold S, Karlawish J, Wolk D, Clark C, Smith C, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Lopez O, Oakley M, Simpson D, Porsteinsson A, Goldstein B, Martin K, Makino K, Ismail M, Brand C, Mulnard R, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Levey A, Lah J, Cellar J, Burns J, Swerdlow R, Brooks W, Apostolova L, Tingus K, Woo E, Silverman D, Lu P, Bartzokis G, Graff-Radford N, Parfitt F, Kendall T, Johnson H, Farlow M, Hake A, Matthews B, Brosch J, Herring S, Hunt C, van Dyck C, Carson R, MacAvoy M, Varma P, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Robin Hsiung G, Feldman H, Mudge B, Assaly M, Finger E, Pasternack S, Rachisky I, Trost D, Kertesz A, Bernick C, Munic D, Mesulam M, Lipowski K, Weintraub S, Bonakdarpour B, Kerwin D, Wu C, Johnson N, Sadowsky C, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Johnson K, Marshall G, Yesavage J, Taylor J, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Sirrel S, Kowall N, Killiany R, Budson A, Norbash A, Johnson P, Obisesan T, Wolday S, Allard J, Lerner A, Ogrocki P, Tatsuoka C, Fatica P, Fletcher E, Maillard P, Olichney J, DeCarli C, Carmichael O, Kittur S, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Burke A, Trncic N, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre D, Kataki M, Adeli A, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Flashman L, Seltzer M, Hynes M, Santulli R, Sink K, Gordineer L, Williamson J, Garg P, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Perry D, Mintzer J, Spicer K, Bachman D, Finger E, Pasternak S, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz S, Boles Ponto L, Shim H, Smith K, Relkin N, Chaing G, Lin M, Ravdin L, Smith A, Raj B, Fargher K. Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline. Neurology 2017, 89: 2176-2186. PMID: 29070667, PMCID: PMC5696639, DOI: 10.1212/wnl.0000000000004670.Peer-Reviewed Original ResearchConceptsMini-Mental State ExaminationDisease Assessment ScaleClinical declineAlzheimer's diseaseBaseline executive functionTau neuropathologyHippocampal volumeAD subtypesMRI scansAlzheimer's Disease Assessment ScaleClinical Dementia Rating SumF-fluorodeoxyglucose (FDG) PETBaseline clinical measuresFunctional Assessment QuestionnaireBaseline hippocampal volumeBaseline MRI scansAlzheimer's Disease Neuroimaging Initiative-1Amyloid-positive participantsVolumetric MRI scansExecutive functionAtrophy subtypesHippocampal atrophyClinical variablesCDR-SBADAS-Cog
2011
Suitability 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 change
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