2024
Generation of Synthetic brain PET images of synaptic density from MRI and FDG-PET using a Multi-stage U-Net
Zheng X, Worhunsky P, Liu Q, Zhou B, Chen X, Guo X, Xie H, Sun H, Zhang J, Toyonaga T, Mecca A, O’Dell R, van Dyck C, Carson R, Radhakrishnan R, Liu C. Generation of Synthetic brain PET images of synaptic density from MRI and FDG-PET using a Multi-stage U-Net. 2024, 00: 1-2. DOI: 10.1109/nss/mic/rtsd57108.2024.10655600.Peer-Reviewed Original ResearchSelf‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort
Miller A, Sharp E, Wang S, Zhao Y, Mecca A, van Dyck C, O'Dell R, Initiative F. Self‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort. Alzheimer's & Dementia 2024, 20: 7847-7858. PMID: 39324520, DOI: 10.1002/alz.14252.Peer-Reviewed Original ResearchSelf-reported hearing lossFunctional Activities QuestionnaireHearing lossMild cognitive impairmentModifiable risk factorsMild cognitive impairment participantsFunctional declineImpairment diagnosisModified Preclinical Alzheimer Cognitive CompositeRate of functional declineRate of cognitive declinePreclinical Alzheimer Cognitive CompositeRisk factorsCognitive impairmentSignificant longitudinal associationsActivity QuestionnaireLongitudinal associationsAlzheimer's Disease Neuroimaging InitiativeLongitudinal relationshipCognitive compositeCN participantsIncreased riskCognitive declineParticipantsDiagnostic conversionValidation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET
Young J, O’Dell R, Naganawa M, Toyonaga T, Chen M, Nabulsi N, Huang Y, Cooper E, Miller A, Lam J, Bates K, Ruan A, Nelsen K, Salardini E, Carson R, van Dyck C, Mecca A. Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET. Journal Of Nuclear Medicine 2024, 65: jnumed.124.267419. PMID: 39299782, PMCID: PMC11533916, DOI: 10.2967/jnumed.124.267419.Peer-Reviewed Original ResearchDistribution volume ratioSUV ratioSynaptic densityEffect sizeAlzheimer's diseaseLongitudinal study of Alzheimer's diseaseMethods:</b> ParticipantsLongitudinal studyMeasure synaptic densityAD participantsStudy of Alzheimer's diseaseNormal cognitionReference regionOlder adultsMulticenterDensity alterationsMeasuring clinically relevant change in apathy symptoms in ADMET and ADMET 2.
Tumati S, Herrmann N, Perin J, Rosenberg P, Lerner A, Mintzer J, Padala P, Brawman-Mintzer O, van Dyck C, Porsteinsson A, Craft S, Levey A, Shade D, Lanctôt K. Measuring clinically relevant change in apathy symptoms in ADMET and ADMET 2. International Psychogeriatrics 2024, 1-13. PMID: 39297292, DOI: 10.1017/s1041610224000711.Peer-Reviewed Original ResearchDementia Apathy Interview and RatingMinimal clinically important differenceDistribution-based analysisMeasure clinically relevant changesClinically important differenceClinically significant apathyAnchor-based analysesDementia careGlobal Impression of ChangeImpression of ChangeLinear mixed modelsAlzheimer's diseaseClinically relevant changesMMSE scoreImportant differenceApathy symptomsApathy ScaleControlled trialsSignificant apathyAnchor measuresDementiaStudy visitsApathy severityMethylphenidate trialSymptom severityKey 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: 870-881. 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 riskCT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease
Lizama B, Williams C, North H, Pandey K, Duong D, Di V, Mecca A, Blennow K, Zetterberg H, Levey A, Grundman M, van Dyck C, Caggiano A, Seyfried N, Hamby M. CT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 6860-6880. PMID: 39166791, PMCID: PMC11485314, DOI: 10.1002/alz.14152.Peer-Reviewed Original ResearchVolumetric magnetic resonance imagingMagnetic resonance imagingPharmacodynamic biomarkersMeta-analysisClinical developmentCerebrospinal fluidPhase 2 clinical trialResonance imagingAlzheimer's diseaseMechanism of actionClinical trialsTandem mass tag-mass spectrometryClinical cohortMild to moderate ADCandidate biomarkersCT1812CohortBiomarker signaturesBiomarkersProteomic findingsUnbiased analysisNetwork analysisAmyloid-betaSynaptic biologyBiological impactCorrection: 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 visitsUpdated 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, 147: 3395-3408. PMID: 38454550, PMCID: PMC11449129, 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 Research