2024
Correction: 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. Correction: Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 159. PMID: 38987826, PMCID: PMC11234521, DOI: 10.1186/s13195-024-01507-7.Peer-Reviewed Original ResearchAdverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial)
Zeng L, Perin J, Gross A, Shade D, Lanctôt K, Lerner A, Mintzer J, Brawman‐Mintzer O, Padala P, van Dyck C, Porsteinsson A, Craft S, Levey A, Herrmann N, Rosenberg P. Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial). International Journal Of Geriatric Psychiatry 2024, 39: e6108. PMID: 38858522, PMCID: PMC11265565, DOI: 10.1002/gps.6108.Peer-Reviewed Original ResearchConceptsMethylphenidate groupTreating apathyPlacebo-controlled trial of methylphenidateTreatment of apathyAssociated with methylphenidateEffects of methylphenidateTrial of methylphenidateAlzheimer's diseaseFollow-upNo treatment group differencesAdverse effects of methylphenidateDiastolic blood pressureSymptom ChecklistAdverse eventsTreatment group differencesMonitoring weightMethylphenidate useMethylphenidate treatmentMedical comorbiditiesPlacebo groupParticipantsMethylphenidateGroup differencesPlacebo-controlled trialMonthly visitsKey Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders
Datta D, Yang S, Joyce M, Woo E, McCarroll S, Gonzalez-Burgos G, Perone I, Uchendu S, Ling E, Goldman M, Berretta S, Murray J, Morozov Y, Arellano J, Duque A, Rakic P, O’Dell R, van Dyck C, Lewis D, Wang M, Krienen F, Arnsten A. Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders. JAMA Psychiatry 2024, 81 PMID: 38776078, PMCID: PMC11112502, DOI: 10.1001/jamapsychiatry.2024.1112.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexLayer III pyramidal cellsWorking memoryCognitive disordersNeuronal firingPrimate dorsolateral prefrontal cortexPyramidal cellsSpatial working memoryWorking memory performanceRisk of mental disordersCalcium-related proteinsReduced neuronal firingL-type calcium channel Cav1.2GluN2B-NMDA receptorsL-type calcium channel activityPrefrontal neuronsL-type calcium channel blockerMemory performanceL-type calcium channelsMental disordersRisk of cognitive disordersCognitive behaviorProtein expressionAssociated with increased riskUpdated 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 imagingCommentary on “Study Partner Report of Apathy in Older Adults is Associated with AD Biomarkers: Findings from the Harvard Aging Brain Study”
Khasnavis S, O'Dell R, van Dyck C, Mecca A. Commentary on “Study Partner Report of Apathy in Older Adults is Associated with AD Biomarkers: Findings from the Harvard Aging Brain Study”. American Journal Of Geriatric Psychiatry 2024, 32: 920-921. PMID: 38658231, DOI: 10.1016/j.jagp.2024.03.017.Peer-Reviewed Original ResearchAuthor Correction: Synaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Author Correction: Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 55. PMID: 38472206, PMCID: PMC10933370, DOI: 10.1038/s41531-024-00674-6.Peer-Reviewed Original ResearchSex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation
He J, Cabrera-Mendoza B, De Angelis F, Pathak G, Koller D, Curhan S, Curhan G, Mecca A, van Dyck C, Polimanti R. Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation. Brain 2024, awae077. PMID: 38454550, DOI: 10.1093/brain/awae077.Peer-Reviewed Original ResearchImaging-derived phenotypesHearing difficultiesBrain imaging-derived phenotypesSex-combined analysisLatent causal variable analysesMendelian randomization approachGeneralized linear regression analysisLocal genetic correlation analysisMultivariate generalized linear regression analysisGenome-wide association studiesLatent causal variableGenetic correlation analysisGenetic correlationsLocal genetic correlationMendelian randomizationPeripheral auditory systemOlder adultsGWAS dataLinear regression analysisHealth burdenGenomic regionsAssociation studiesPleiotropic regionsSex differencesTranscriptome regulationNanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration
Datta D, Perone I, Wijegunawardana D, Liang F, Morozov Y, Arellano J, Duque A, Xie Z, van Dyck C, Joyce M, Arnsten A. Nanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration. Alzheimer's & Dementia 2024, 20: 2843-2860. PMID: 38445818, PMCID: PMC11032534, DOI: 10.1002/alz.13737.Peer-Reviewed Original ResearchSynaptic density patterns in early Alzheimer’s disease assessed by independent component analysis
Fang X, Raval N, O’Dell R, Naganawa M, Mecca A, Chen M, van Dyck C, Carson R. Synaptic density patterns in early Alzheimer’s disease assessed by independent component analysis. Brain Communications 2024, 6: fcae107. PMID: 38601916, PMCID: PMC11004947, DOI: 10.1093/braincomms/fcae107.Peer-Reviewed Original ResearchMedial temporal brain regionsAlzheimer's diseaseTemporal brain regionsCognitive deficitsBrain regionsCognitive impairmentPostmortem studiesBinds to SV2ASynaptic densityReduction of synaptic densityIndependent component analysisSynaptic lossAlzheimerDeficitsImpairmentBrainNeocortexComponent analysisPrimary pathologySV2ASynaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse lossExamining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease
Wang G, Li Y, Xiong C, Benzinger T, Gordon B, Hassenstab J, Aschenbrenner A, McDade E, Clifford D, Libre‐Guerra J, Shi X, Mummery C, van Dyck C, Lah J, Honig L, Day G, Ringman J, Brooks W, Fox N, Suzuki K, Levin J, Jucker M, Delmar P, Bittner T, Bateman R, Team F. Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease. Alzheimer's & Dementia 2024 PMID: 38400532, DOI: 10.1002/alz.13735.Peer-Reviewed Original ResearchLatent classesPositron emission tomographyAmyloid reductionCognitive efficacyLatent class analysisAmyloid positron emission tomographyCognitive outcomesCognitive declineDominantly Inherited Alzheimer's Network Trials UnitSurrogate biomarkerBaseline characteristicsInherited Alzheimer's diseaseMultiple measuresClass analysisEmission tomographyTrials UnitAlzheimer's diseaseClinical trialsSurrogate endpointsTreatment effectsWhole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease
Xicota L, Cosentino S, Vardarajan B, Mayeux R, Perls T, Andersen S, Zmuda J, Thyagarajan B, Yashin A, Wojczynski M, Krinsky‐McHale S, Handen B, Christian B, Head E, Mapstone M, Schupf N, Lee J, Barral S, Study T, Abner E, Adams P, Aguirre A, Albert M, Albin R, Allen M, Alvarez L, Andrews H, Apostolova L, Arnold S, Asthana S, Atwood C, Ayres G, Barber R, Barnes L, Barral S, Bartlett J, Beach T, Becker J, Beecham G, Benchek P, Bennett D, Bertelson J, Biber S, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Brewer J, Burke J, Burns J, Bush W, Buxbaum J, Byrd G, Cantwell L, Cao C, Carlsson C, Carrasquillo M, Chan K, Chasse S, Chen Y, Chesselet M, Chin N, Chui H, Chung J, Craft S, Crane P, Cranney M, Cruchaga C, Cuccaro M, Culhane J, Cullum C, Darby E, Davis B, De Jager P, DeCarli C, DeToledo J, Dickson D, Dobbins N, Duara R, Ertekin‐Taner N, Evans D, Faber K, Fairchild T, Fallin D, Fallon K, Fardo D, Farlow M, Farrell J, Farrer L, Fernandez‐Hernandez V, Foroud T, Frosch M, Galasko D, Gamboa A, Gauthreaux K, Gefen T, Geschwind D, Ghetti B, Gilbert J, Goate A, Grabowski T, Graff‐Radford N, Griswold A, Haines J, Hakonarson H, Hall K, Hall J, Hamilton R, Hamilton‐Nelson K, Han X, Harari O, Hardy J, Harrell L, Head E, Henderson V, Hernandez M, Honig L, Huebinger R, Huentelman M, Hulette C, Hyman B, Hynan L, Ibanez L, Jarvik G, Jayadev S, Jin L, Johnson K, Johnson L, Jones B, Jun G, Kamboh M, Kang M, Karydas A, Katz M, Kauwe J, Kaye J, Keene C, Keller B, Khaleeq A, Kim R, Knebl J, Kowall N, Kramer J, Kukull W, Kunkle B, Kuzma A, LaFerla F, Lah J, Larson E, Lerch M, Lerner A, Leung Y, Leverenz J, Levey A, Lieberman A, Lipton R, Lopez O, Lunetta K, Lyketsos C, Mains D, Manly J, Mark L, Marquez D, Marson D, Martin E, Masliah E, Massman P, Masurkar A, Mayeux R, McCormick W, McCurry S, McDonough S, McKee A, Mesulam M, Mez J, Miller B, Miller C, Mock C, Moghekar A, Montine T, Monuki E, Mooney S, Morris J, Mukherjee S, Myers A, Naj A, Nguyen T, Noble J, Nudelman K, O'Bryant S, Ormsby K, Ory M, Palmer R, Parisi J, Paulson H, Pavlik V, Paydarfar D, Perez V, Pericak‐Vance M, Petersen R, Polk M, Qu L, Quiceno M, Quinn J, Raj A, Rajabli F, Ramanan V, Reiman E, Reisch J, Reitz C, Ringman J, Roberson E, Rodriguear M, Rogaeva E, Rosen H, Rosenberg R, Royall D, Sano M, Saykin A, Schellenberg G, Schneider J, Schneider L, Seeley W, Sherva R, Shibata D, Small S, Smith A, Smith J, Song Y, Spina S, St George‐Hyslop P, Stern R, Stevens A, Strittmatter S, Sultzer D, Swerdlow R, Teich A, Tilson J, Tosto G, Trojanowski J, Troncoso J, Tsuang D, Valladares O, Van Deerlin V, Van Dyck C, Van Eldik L, Vance J, Vardarajan B, Vassar R, Vinters H, Wang L, Weintraub S, Welsh‐Bohmer K, Wheeler N, Wijsman E, Wilhelmsen K, Williams B, Williamson J, Wilms H, Wingo T, Wisniewski T, Woltjer R, Woon M, Younkin S, Yu L, Zhao Y, Zhou X, Zhu C, Aizenstein H, Ances B, Andrews H, Bell K, Birn R, Brickman A, Bulova P, Cheema A, Chen K, Christian B, Clare I, Cohen A, Constantino J, Doran E, Fagan A, Feingold E, Foroud T, Handen B, Harp J, Hartley S, Head E, Henson R, Hom C, Honig L, Ikonomovic M, Johnson S, Jordan C, Kamboh M, Keator D, Klunk W, Kofler J, Krinsky‐McHale S, Lai F, Lao P, Laymon C, Lee J, Lott I, Lupson V, Mapstone M, Mathis C, Minhas D, Nadkarni N, O'Bryant S, Parisi M, Pang D, Petersen M, Price J, Pulsifer M, Rafii M, Reiman E, Rizvi B, Rosas H, Ryan L, Schmitt F, Schupf N, Silverman W, Tudorascu D, Tumuluru R, Varadarajan B, White D, Yassa M, Zaman S, Zhang F. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 2670-2679. PMID: 38380866, PMCID: PMC11032545, DOI: 10.1002/alz.13718.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseGenes associated with late-onset Alzheimer's diseaseLate-onset Alzheimer's disease riskSeveral single nucleotide polymorphismsVariants associated with late-onset Alzheimer diseaseBeta-amyloidIdentified several single nucleotide polymorphismsWhole-genome sequence analysisGenome sequence analysisLevels of beta-amyloidAlzheimer's diseaseTight linkage disequilibriumMicrotubule associated proteinSingle nucleotide polymorphismsFamily studiesCandidate lociMTUS2Linkage disequilibriumSequence analysisAssociation analysisNucleotide polymorphismsGenetic associationAlzheimer's dementiaAssociated proteinGenetic componentA pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligands
2023
Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants
Trainer A, Xu W, Chase A, O'Dell R, Tun S, Li J, Ju S, van Dyck C, Mecca A, Fredricks C. Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079435.Peer-Reviewed Original ResearchAmnestic Alzheimer's diseaseLogopenic variant primary progressive aphasiaPosterior cortical atrophyFunctional connectivity mapsHigher tau burdenFunctional connectivityTau burdenAlzheimer's diseaseConnectivity mapsLongitudinal tau-PETSpread of tauVariant primary progressive aphasiaFusiform gyrusFrontal eye fieldPrimary progressive aphasiaBrains of participantsTau PET scansSuperior parietal lobulePatient-specific biomarkersCortical atrophyCommon subtypeTau-PETHealthy controlsParietooccipital cortexPET scansBlood‐based biomarkers for predicting treatment response in the Apathy in Dementia Methylphenidate Trial 2 randomized clinical trial
Tumati S, Vieira D, Bawa K, Andreazza A, Mintzer J, Scherer R, Rosenberg P, van Dyck C, Padala P, Brawman‐Mintzer O, Porsteinsson A, Lerner A, Craft S, Levey A, Burke W, Perin J, Shade D, Herrmann N, Lanctôt K. Blood‐based biomarkers for predicting treatment response in the Apathy in Dementia Methylphenidate Trial 2 randomized clinical trial. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079161.Peer-Reviewed Original ResearchAnatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Anatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.075998.Peer-Reviewed Original ResearchTau pathologyEntorhinal cortexAlzheimer's diseaseRhesus macaquesBrain tau pathologyHigher brain circuitsHigher cortical circuitsPattern of neurodegenerationAged rhesus macaquesHuman Alzheimer's diseaseSporadic Alzheimer's diseaseTrans-synaptic propagationSoluble tau speciesSequence of tauDorsolateral prefrontal cortexAmyloid pathologyExtracellular spaceDendritic shaftsAdvanced neurodegenerationTau hyperphosphorylationInhibitory synapsesNeurofibrillary tanglesGlutamatergic synapsesSpine apparatusAD biomarkersNatural cubic splines for the analysis of Alzheimer’s trials
Donohue M, Langford O, Insel P, van Dyck C, Petersen R, Craft S, Raman R, Sims J, Sperling R, Aisen P. Natural cubic splines for the analysis of Alzheimer’s trials. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.070862.Peer-Reviewed Original ResearchVersion effectsType I error controlNatural cubic splinesDegrees of freedomPreclinical AlzheimerTreatment effect estimatesType I errorMild dementiaProportional treatment effectLongitudinal data analysisSimulation studyModel selection techniquesMild Alzheimer's dementiaEffect assumptionSpline modelMMRMCubic splinesSplinesA4 studyTrial of donepezilOff-scheduleADAS-CogAlzheimer's dementiaEffect estimatesTreat principleFeasibility Study for Longitudinal Retinal Imaging in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Trial
Rissman R, Ngolab J, Donohue M, Belsha A, Salazar J, Cohen P, Jaiswal S, Tan V, Aggarwal N, Alber J, Johnson K, Jicha G, van Dyck C, Lah J, Salloway S, Rafii M, Aisen P, Sperling R. Feasibility Study for Longitudinal Retinal Imaging in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Trial. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079580.Peer-Reviewed Original ResearchAnti-Amyloid TreatmentAsymptomatic Alzheimer's diseaseFeasibility of retinal imagingLongitudinal Evaluation of Amyloid RiskCohort of individualsAlzheimer's diseaseResults ParticipantsAnti-amyloidA4 trialAD-diagnosed patientsRetinal spotsPositron emission tomographyStandardized uptake value ratioAmyloid positron emission tomographyLongitudinal evaluationRisk detectionClinically normal individualsParticipantsPET standardized uptake value ratioFeasibility studyClinicCross-sectionRetinal amyloid depositsAmyloid depositsIndividualsAging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Young J, Park H, Kim M, Par-Young J, Bartlett H, Kim H, Unlu S, Osmani L, Shin M, Bucala R, van Dyck C, Allore H, Mecca A, You S, Kang I. Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease. Immunity & Ageing 2023, 20: 71. PMID: 38042785, PMCID: PMC10693128, DOI: 10.1186/s12979-023-00396-y.Peer-Reviewed Original ResearchPeripheral bloodT cellsAlzheimer's diseaseEM CD8Memory CD8Gene signatureAge-related immune changesIL-7 receptor alphaEffector memory CD8Strong risk factorT cell expansionAD genesAge-associated expansionImmune changesRisk factorsCD8Dementia patientsIL-7RNeuropsychological testingReceptor alphaNeurocognitive functionRT-qPCR resultsDisease severityPatientsNormal personsP104: Heterogeneity of Response to methylphenidate in apathetic patients in the ADMET 2 Trial
Lanctôt K, Rivet L, Tumati S, Perin J, Vieira D, Rosenberg P, Herrmann N, Lerner A, Padala P, Brawman-Mintzer O, van Dyck C, Porsteinsson A, Craft S, Levey A, Mintzer J. P104: Heterogeneity of Response to methylphenidate in apathetic patients in the ADMET 2 Trial. International Psychogeriatrics 2023, 35: 125-126. DOI: 10.1017/s1041610223002557.Peer-Reviewed Original ResearchPotential predictors of treatment outcomePredictors of treatment outcomeResponse to methylphenidateClinically significant apathyAlzheimer's Disease Cooperative Study ActivitiesMedium effect sizeMonths of methylphenidateAlzheimer's diseaseNPI-aMethylphenidate treatmentSignificant apathyApathetic patientsBaseline anxietyAD participantsMethylphenidatePotential predictorsActivities of Daily Living ScaleCompared to placeboNeuropsychiatric symptomsIndex scoreDaily Living ScaleAlzheimer's Disease Cooperative Study Activities of Daily Living ScaleApathyEffect sizeLiving scale