2025
Effects 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, Léger 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 problemsEffects of exercise versus usual care on older adults with amnestic mild cognitive impairment: EXERT versus ADNI
Shadyab A, Aslanyan V, Jacobs D, Salmon D, Morrison R, Katula J, Jin S, Thomas R, LaCroix A, Pa J, Cotman C, Feldman H, Baker L, Group F. Effects of exercise versus usual care on older adults with amnestic mild cognitive impairment: EXERT versus ADNI. Alzheimer's & Dementia 2025, 21: e70118. PMID: 40271887, PMCID: PMC12019695, DOI: 10.1002/alz.70118.Peer-Reviewed Original ResearchConceptsUsual careRandomized controlled trialsAmnestic mild cognitive impairmentOlder adultsMild cognitive impairmentADNI-1Multisite randomized controlled trialNo interventionSedentary older adultsIntensity aerobic trainingAlzheimer's Disease Neuroimaging Initiative 1Moderate-high intensityEffects of exerciseCognitive declineCognitive impairmentFlexibility exercisesExercise armAerobic trainingAD-signature regionsExertion groupCognitive trajectoriesExertionCarePost hoc analysisExerciseUse 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 abnormalitiesevoke 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 eventsComparison of eligibility criteria and baseline characteristics between the patient populations of evoke and evoke+, Clarity AD, and TRAILBLAZER‐ALZ‐2
Feldman H, Scheltens P, Hansson O, Sano M, van der Flier W, Bardtrum L, Johannsen P, Jeppesen R, Leon T, Hansen C, Cummings J. Comparison of eligibility criteria and baseline characteristics between the patient populations of evoke and evoke+, Clarity AD, and TRAILBLAZER‐ALZ‐2. Alzheimer's & Dementia 2024, 20: e083684. PMCID: PMC11713343, DOI: 10.1002/alz.083684.Peer-Reviewed Original ResearchClinical Dementia RatingNon-white participantsPositron emission tomographyEarly-stage AD patientsAlzheimer's diseaseMini-Mental State ExaminationMild AD dementiaMild cognitive impairmentTau positron emission tomographyEpisodic memoryGlucagon-like peptide-1 receptor agonist semaglutidePlacebo-controlled trialInclusion criteriaTau pathologyCDR sumCognitive impairmentMini-MentalState ExaminationDementia RatingImpaired patientsAD patientsGlobal scoreAmyloid positivityTrial populationDisease-modifying therapiesRegional differences in baseline demographic and clinical characteristics from the evoke and evoke+ trials of semaglutide for early Alzheimer’s disease
van der Flier W, Scheltens P, Feldman H, Hansson O, Sano M, Bardtrum L, Johannsen P, Jeppesen R, Hansen C, Leon T, Cummings J. Regional differences in baseline demographic and clinical characteristics from the evoke and evoke+ trials of semaglutide for early Alzheimer’s disease. Alzheimer's & Dementia 2024, 20: e088793. PMCID: PMC11713752, DOI: 10.1002/alz.088793.Peer-Reviewed Original ResearchMini-Mental State Examination scoreBaseline dataCognitive scoresClinical Dementia Rating-SumAlzheimer's diseaseApolipoprotein E4 carrier statusClinical Dementia Rating-Sum of Boxes scoresInclusion of participantsMild cognitive impairmentScreening failure rateProportion of individualsMild dementiaGeographic regionsType 2 diabetesBox scoresAD medicationsClinical characteristicsInclusion criteriaCarrier statusNorth AmericaExamination scoresClinical trial populationsPatient characteristicsCognitive impairmentSmall vessel pathologyA 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 impairmentParticipants
2023
CSF tau markers are associated with fine memory discrimination in older adults with amnestic MCI in the EXERT trial
Fenton L, Aslanyan V, Jacobs D, Salmon D, Brewer J, Rissman R, Feldman H, Shadyab A, LaCroix A, Baker L, Pa J. CSF tau markers are associated with fine memory discrimination in older adults with amnestic MCI in the EXERT trial. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.080157.Peer-Reviewed Original ResearchAmnestic mild cognitive impairmentMemory discriminationOlder adultsMemory testLogical memoryHippocampal volumeAuditory Verbal Learning TestLogical memory testVerbal Learning TestBehavioral pattern separationVerbal memory testsMedial temporal lobeLarger hippocampal volumesMemory measuresList learningStory recallLearning TestObject taskMemory assessmentCognitive performanceMild cognitive impairmentPattern separationCognitive AssessmentStructural brain imagesTemporal lobe
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