2025
Use of lecanemab and donanemab in the Canadian healthcare system: Evidence, challenges, and areas for future research
Smith E, Phillips N, Feldman H, Borrie M, Ganesh A, Henri-Bhargava A, Desmarais P, Frank A, Badhwar A, Barlow L, Bartha R, Best S, Bethell J, Bhangu J, Black S, Bocti C, Bronskill S, Burhan A, Calon F, Camicioli R, Campbell B, Collins D, Dadar M, DeMarco M, Ducharme S, Duchesne S, Einstein G, Fisk J, Gawryluk J, Grossman L, Ismail Z, Itzhak I, Joshi M, Harrison A, Kröger E, Kumar S, Laforce R, Lanctot K, Lau M, Lee L, Masellis M, Massoud F, Mitchell S, Montero-Odasso M, Barnett K, Nygaard H, Pasternak S, Peters J, Rajah M, Robillard J, Rockwood K, Rosa-Neto P, Seitz D, Soucy J, Trenaman S, Wellington C, Zadem A, Chertkow H, Investigators C. Use of lecanemab and donanemab in the Canadian healthcare system: Evidence, challenges, and areas for future research. The Journal Of Prevention Of Alzheimer's Disease 2025, 12: 100068. PMID: 39893139, PMCID: PMC12184013, DOI: 10.1016/j.tjpad.2025.100068.Peer-Reviewed Original ResearchConceptsCanadian healthcare systemStatistically significant group differencesAlzheimer's diseaseMild cognitive impairmentMild dementiaHealthcare systemStage of mild cognitive impairmentQuality evidenceSignificant group differencesMonoclonal antibody therapyTrial publicationsCerebrospinal fluid analysisCognitive impairmentCanadian ConsortiumGroup differencesPositron emission tomographyAntibody therapyImaging abnormalitiesTreatment populationClinical trialsIndividual patientsReview evidenceClinical relevanceTherapyAmyloid-related imaging abnormalitiesAnti-Amyloid Therapies for Alzheimer’s Disease and Amyloid-Related Imaging Abnormalities: Implications for the Emergency Medicine Clinician
Rech M, Carpenter C, Aggarwal N, Hwang U. Anti-Amyloid Therapies for Alzheimer’s Disease and Amyloid-Related Imaging Abnormalities: Implications for the Emergency Medicine Clinician. Annals Of Emergency Medicine 2025, 85: 526-536. PMID: 39818674, DOI: 10.1016/j.annemergmed.2024.12.002.Peer-Reviewed Original ResearchEmergency medicine cliniciansAnti-amyloid therapiesCases of dementiaEmergency department visitsAlzheimer's diseaseDepartment visitsIschemic stroke patientsStroke patientsIncreased riskAlzheimer's disease progressionCliniciansRisk of adverse effectsAnti-amyloidDisease-modifying treatmentsAmyloid-relatedNeurodegenerative disordersImaging abnormalitiesAlzheimerAdverse effectsEmergencyDementiaAmyloid-related imaging abnormalities
2024
Updated 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 imagingSafety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer’s disease
Hajós M, Boasso A, Hempel E, Shpokayte M, Konisky A, Seshagiri C, Fomenko V, Kwan K, Nicodemus-Johnson J, Hendrix S, Vaughan B, Kern R, Megerian J, Malchano Z. Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer’s disease. Frontiers In Neurology 2024, 15: 1343588. PMID: 38515445, PMCID: PMC10957179, DOI: 10.3389/fneur.2024.1343588.Peer-Reviewed Original ResearchAssessment of adverse eventsMild to moderate ADGamma oscillationsModerate ADAmyloid-related imaging abnormalitiesAlzheimer's diseaseMild-to-moderate Alzheimer's diseaseSecondary clinical outcome measuresTherapy systemPrimary outcome measureHigher adherence ratesWhole-brain volumeClinical outcome measuresSecondary outcome measuresModerate Alzheimer's diseaseDisease-modifying effectsBaseline MMSE scoreStudy discontinuationExperimental AD modelsWell-toleratedEfficacy outcomesClinical benefitAdverse eventsDaily treatmentClinical criteria
2023
Trial of Solanezumab in Preclinical Alzheimer’s Disease
Sperling R, Donohue M, Raman R, Rafii M, Johnson K, Masters C, van Dyck C, Iwatsubo T, Marshall G, Yaari R, Mancini M, Holdridge K, Case M, Sims J, Aisen P. Trial of Solanezumab in Preclinical Alzheimer’s Disease. New England Journal Of Medicine 2023, 389: 1096-1107. PMID: 37458272, PMCID: PMC10559996, DOI: 10.1056/nejmoa2305032.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesPreclinical Alzheimer's diseasePositron emission tomographyBrain amyloid levelsPlacebo groupAmyloid levelsAlzheimer's diseaseF-florbetapir positron emission tomographyGlobal Clinical Dementia Rating (CDR) scoreMini-Mental State ExaminationPrimary end pointClinical Dementia Rating scorePhase 3 trialPreclinical Alzheimer's cognitive composite scoresDementia Rating scoreYears of ageForms of amyloidBrain positron emission tomographyImaging abnormalitiesCognitive composite scoreMean ageFamily historyMean changePersons 65State ExaminationInvestigating Partially Discordant Results in Phase 3 Studies of Aducanumab
Mallinckrodt C, Tian Y, Aisen P, Barkhof F, Cohen S, Dent G, Hansson O, Harrison K, Iwatsubo T, Mummery C, Muralidharan K, Nestorov I, Nisenbaum L, Rajagovindan R, von Hehn C, van Dyck C, Vellas B, Wu S, Zhu Y, Sandrock A, Chen T, Haeberlein S. Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab. The Journal Of Prevention Of Alzheimer's Disease 2023, 10: 171-177. PMID: 36946443, DOI: 10.14283/jpad.2023.6.Peer-Reviewed Original ResearchConceptsHigh-dose armAmyloid-related imaging abnormalitiesPhase 3 studyBaseline characteristicsImaging abnormalitiesAlzheimer's diseaseDiscordant resultsParallel-group studyHigh-dose groupMild AD dementiaEarly Alzheimer's diseaseMild cognitive impairmentSecondary endpointsTreatment armsAD dementiaAmyloid pathologyMulticenter studyRapid progressionSignificant treatment effectSafety resultsTarget dosePatientsAducanumabCognitive impairmentNon-significant difference
2022
Lecanemab in Early Alzheimer’s Disease
van Dyck C, Swanson C, Aisen P, Bateman R, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer L, Iwatsubo T. Lecanemab in Early Alzheimer’s Disease. New England Journal Of Medicine 2022, 388: 9-21. PMID: 36449413, DOI: 10.1056/nejmoa2212948.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseasePositron emission tomographyDisease Assessment ScaleAlzheimer's diseaseAmyloid burdenAlzheimer's Disease Cooperative Study-ActivitiesAmyloid-related imaging abnormalitiesKey secondary end pointEnd pointAlzheimer's Disease Assessment ScaleClinical Dementia Rating SumHumanized IgG1 monoclonal antibodyMarkers of amyloidInfusion-related reactionsPrimary end pointSecondary end pointsCerebrospinal fluid testingPhase 3 trialBrain amyloid burdenDaily Living ScaleEvidence of amyloidCDR-SB scoresYears of ageMild cognitive impairmentIgG1 monoclonal antibodyAlzheimer disease neuropathology in a patient previously treated with aducanumab
Plowey ED, Bussiere T, Rajagovindan R, Sebalusky J, Hamann S, von Hehn C, Castrillo-Viguera C, Sandrock A, Budd Haeberlein S, van Dyck CH, Huttner A. Alzheimer disease neuropathology in a patient previously treated with aducanumab. Acta Neuropathologica 2022, 144: 143-153. PMID: 35581440, PMCID: PMC9217863, DOI: 10.1007/s00401-022-02433-4.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesLong-term extensionStandard uptake value ratioAlzheimer's diseaseAmyloid positron emission tomographyBraak stage VPhase 1b studyPhospho-tau immunohistochemistryPostmortem neuropathologic examinationSpecies of AβAD neuropathologic changeFirst autopsy reportAlzheimer's disease neuropathologyUptake value ratioAmyloid PET scanMild Alzheimer's diseasePositron emission tomographyLast doseReactive microgliaNeuropathologic evidenceNeuropathologic examinationPlacebo armImaging abnormalitiesMonthly dosesNeuropathologic changes
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
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