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 trialsEffects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study
Baker L, Pa J, Katula J, Aslanyan V, Salmon D, Jacobs D, Chmelo E, Hodge H, Morrison R, Matthews G, Brewer J, Jung Y, Rissman R, Taylor C, LĂ©ger G, Messer K, Evans A, Okonkwo O, Shadyab A, Zou J, Jin S, Thomas R, Zhang J, La Croix A, Cotman C, Feldman H, Group F. Effects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study. Alzheimer's & Dementia 2025, 21: e14586. PMID: 40271888, PMCID: PMC12019696, DOI: 10.1002/alz.14586.Peer-Reviewed Original ResearchConceptsSedentary older adultsAmnestic mild cognitive impairmentIntensity aerobic trainingMild cognitive impairmentEffects of exerciseRandomized controlled trialsIntervention deliveryAerobic trainingOlder adultsMonths of supervised exerciseCognitive impairmentMultisite randomized controlled trialCognitive trajectoriesLower-intensity exerciseMeasure of global cognitive functionRandomized controlled trials of adultsTests of executive functionIntervention group differencesMeasures of brain healthAssess intervention efficacyGlobal cognitive functionGlobal cognitive compositeMild cognitive impairment groupSupervised exerciseMild memory problemsTailoring implementation strategies for the healthy actions and lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia Program: Lessons learned from a survey study
Moukarzel S, Araujo-Menendez C, Galang E, Zlatar Z, Feldman H, Banks S, Group H. Tailoring implementation strategies for the healthy actions and lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia Program: Lessons learned from a survey study. The Journal Of Prevention Of Alzheimer's Disease 2025, 12: 100053. PMID: 39827004, PMCID: PMC12184062, DOI: 10.1016/j.tjpad.2024.100053.Peer-Reviewed Original ResearchConceptsModifiable risk factorsNon-HispanicHealthy actionsCross-sectional study SETTINGTailored implementation strategiesDecreased dementia riskProgram participantsAssociated with higher interestSelf-administered surveySelf-rated satisfactionDementia programsDementia riskTailored ImplementationMixed-methods analysisIndependent of ethnicityExploratory factor analysisSociodemographic characteristicsOlder adultsStudy settingThematic analysisLifestyle changesProgram enrollmentIn-personProgram implementationImplementation strategiesevoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer’s disease
Cummings J, Atri A, Feldman H, Hansson O, Sano M, Knop F, Johannsen P, León T, Scheltens P. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer’s disease. Alzheimer's Research & Therapy 2025, 17: 14. PMID: 39780249, PMCID: PMC11708093, DOI: 10.1186/s13195-024-01666-7.Peer-Reviewed Original ResearchConceptsSymptomatic ADAlzheimer's diseaseDouble-blindGlucagon-like peptide-1 receptor agonist semaglutidePlacebo-controlled phase 3 trialOnce-daily oral semaglutideClinical Dementia RatingMild cognitive impairmentAD-related processesAD biomarkersSafety of semaglutideDose-escalation regimenPhase 3 studyBaseline to weekEffect of semaglutidePhase 3 trialCognitive impairmentPathophysiology of Alzheimer's diseasePotential disease-modifying effectsDementia RatingSymptomatic Alzheimer's diseaseTreatment of type 2 diabetesPlacebo-controlledType 2 diabetesDisease-modifying potential
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 eventsPost hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer’s disease, positive for plasma p-tau217
Kovacech B, Cullen N, Novak P, Hanes J, Kontsekova E, Katina S, Parrak V, Fresser M, Vanbrabant J, Feldman H, Winblad B, Stoops E, Vanmechelen E, Zilka N. Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer’s disease, positive for plasma p-tau217. Alzheimer's Research & Therapy 2024, 16: 254. PMID: 39580468, PMCID: PMC11585249, DOI: 10.1186/s13195-024-01620-7.Peer-Reviewed Original ResearchConceptsClinical Dementia Rating-Sum of BoxesPhase 2 clinical trialGlial fibrillary acidic proteinPost hoc analysisAlzheimer's diseaseAlzheimer's Disease Cooperative Study ActivitiesPlasma p-tau217Clinical Dementia Rating-SumClinical trialsWhole-brain volumeSpread of tau pathologyPlasma biomarkers of neurodegenerationPlasma P-tau217 levelsMicrotubule-binding regionSubgroup of participantsADAMS participantsTau pathologyAD-related neuropathological changesCognitive declineFibrillary acidic proteinActive immunotherapyDouble-blindPlacebo-controlledVolumetric MRITau immunotherapyA multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease
Galasko D, Farlow M, Lucey B, Honig L, Elbert D, Bateman R, Momper J, Thomas R, Rissman R, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman H. A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease. Alzheimer's Research & Therapy 2024, 16: 151. PMID: 38970127, PMCID: PMC11225352, DOI: 10.1186/s13195-024-01490-z.Peer-Reviewed Original ResearchConceptsOrally administered small moleculeFractional synthesis rateAscending dose studyDose-dependent loweringIRB-approved protocolEarly ADMini-Mental State ExamDose-dependent effectAlzheimer's diseaseBlood patchDouble-blindWell-toleratedCatheter placementPreclinical modelsLumbar punctureDose studyIntravenous infusionMild cognitive impairmentEvaluate safetyPlacebo participantsCognitive measuresStable isotope labeling kineticsActive drugClinical trialsADAS-Cog12Asian Cohort for Alzheimer Disease (ACAD) Pilot Study
Peavy G, Võ N, Revta C, Lu A, Lupo J, Nam P, Nguyễn K, Wang L, Feldman H. Asian Cohort for Alzheimer Disease (ACAD) Pilot Study. Alzheimer Disease & Associated Disorders 2024, 38: 277-284. PMID: 39177172, PMCID: PMC11340683, DOI: 10.1097/wad.0000000000000631.Peer-Reviewed Original ResearchConceptsSubjective cognitive complaintsOlder Vietnamese AmericansVascular risk factorsMild cognitive impairmentVietnamese AmericansRisk factorsMeasuring subjective cognitive complaintsPilot studyCommunity advisory boardNongenetic risk factorsCommunity-based researchAD risk factorsAlzheimer's diseaseDepressive symptomsConsensus teamCognitive complaintsBilingual/bicultural staffAD riskAssessment toolAdvisory boardVietnamese communityExploratory analysisCognitive difficultiesCognitive impairmentParticipantsProtocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam)
Feldman H, Luchsinger J, Léger G, Taylor C, Jacobs D, Salmon D, Edland S, Messer K, Revta C, Flowers S, Jones K, Koulman A, Yarasheski K, Verghese P, Venkatesh V, Zetterberg H, Durant J, Lupo J, Gibson G, Group F. Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam). PLOS ONE 2024, 19: e0302998. PMID: 38809849, PMCID: PMC11135745, DOI: 10.1371/journal.pone.0302998.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlzheimer DiseaseDouble-Blind MethodFemaleHumansMaleMiddle AgedProdrugsThiamineTreatment OutcomeConceptsPhase 2bPhase 2aRandomized double-blind placebo-controlled trialDouble-blind placebo-controlled trialCo-primary efficacy endpointsTolerability eventsBest-tolerated dosePlacebo-controlled trialWell-tolerated dosesAlzheimer's diseaseLonger-term safetyEfficacy of drug deliveryWeeks of treatmentTargeted therapeutic approachesErythrocyte transketolase activityGroups of participantsDouble-blindPlacebo armEfficacy endpointSecondary endpointsOral treatmentPharmacokinetic measurementsClinical trialsTherapeutic approachesBlood markers
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply