2024
Relationship between neuroimaging and cognition in frontotemporal dementia: An FDG‐PET and structural MRI study
Cayir S, Volpi T, Toyonaga T, Gallezot J, Yang Y, Sadabad F, Mulnix T, Mecca A, Fesharaki‐Zadeh A, Matuskey D. Relationship between neuroimaging and cognition in frontotemporal dementia: An FDG‐PET and structural MRI study. Journal Of Neuroimaging 2024 PMID: 38676301, DOI: 10.1111/jon.13206.Peer-Reviewed Original ResearchMoCA scoresFDG-PETAssociation of cognitionStandardized uptake value ratioMontreal Cognitive AssessmentSignificant positive associationFrontotemporal dementiaPrimary outcome measurePosterior cingulate cortexDecline of cognitive functionYears of ageGM volumeFrontal cortexOutcome measuresCognitive dysfunctionGray matterCognitive AssessmentMoCAAssociated with cognitive dysfunctionFluorodeoxyglucose (FDG)-PETPositive associationMagnetic resonance imagingPartial volume correctionCognitive functionDementiaInvestigating the Relationships of Atrophy and Hypometabolism on Cognitive Decline in Frontotemporal Dementia (P1-9.018)
Cayir S, Yang Y, Volpi T, Sadabad F, Toyonaga T, Gallezot J, Mecca A, Fesharaki-Zadeh A, Matuskey D. Investigating the Relationships of Atrophy and Hypometabolism on Cognitive Decline in Frontotemporal Dementia (P1-9.018). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000204352.Peer-Reviewed Original ResearchCommentary 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 regulationSynaptic 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 lossAssessment of disparities in timely diagnosis and comprehensive workup of cognitive impairment between English and Spanish speakers
Silva-Rudberg J, Carrión C, Pérez-Palmer N, Li J, Mehta S, Diab N, Mecca A, O'Dell R. Assessment of disparities in timely diagnosis and comprehensive workup of cognitive impairment between English and Spanish speakers. American Journal Of Geriatric Psychiatry 2024, 32: 773-786. PMID: 38336573, PMCID: PMC11162952, DOI: 10.1016/j.jagp.2024.01.030.Peer-Reviewed Original ResearchDiagnosis of mild cognitive impairmentSpanish-speaking patientsMild cognitive impairmentHispanic/Latino patientsCognitive impairmentNon-English language preferenceLanguage preferenceComprehension of diagnosisImpact of language barriersAssessment of disparitiesDiagnosis of cognitive impairmentSpanish language preferenceDiagnosis of dementiaElectronic medical recordsCross-sectional studyTimeliness of diagnosisDementia careRetrospective cross-sectional studyDementia diagnosisHealth disparitiesU.S. Hispanic/Latino populationBinomial logistic regressionNeighborhood disadvantageSpanish speakersHealth careA 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 scansDementia risk analysis using temporal event modeling on a large real-world dataset
Taylor R, Gilson A, Chi L, Haimovich A, Crawford A, Brandt C, Magidson P, Lai J, Levin S, Mecca A, Hwang U. Dementia risk analysis using temporal event modeling on a large real-world dataset. Scientific Reports 2023, 13: 22618. PMID: 38114545, PMCID: PMC10730574, DOI: 10.1038/s41598-023-49330-8.Peer-Reviewed Original ResearchAging 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 personsThe regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J
Toyonaga T, Khattar N, Wu Y, Lu Y, Naganawa M, Gallezot J, Matuskey D, Mecca A, Pittman B, Dias M, Nabulsi N, Finnema S, Chen M, Arnsten A, Radhakrishnan R, Skosnik P, D’Souza D, Esterlis I, Huang Y, van Dyck C, Carson R. The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 1012-1022. PMID: 37955791, DOI: 10.1007/s00259-023-06487-8.Peer-Reviewed Original ResearchSynaptic densityAge-related decreaseMagnetic resonance imagingBlood flowAge-related synaptic lossGray matter volume lossSynaptic density lossPositron emission tomography (PET) ligandSynaptic vesicle glycoprotein 2AVivo PET measurementsMedial occipital cortexGray matter volumeAge-related neurodegenerationGray matter regionsCognitive normal subjectsAge-related changesSynaptic lossNerve terminalsWide age rangeOccipital cortexTomography ligandNormal subjectsGM volumeAge-related functional lossesMatter volumeAssessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET
Silva-Rudberg J, Salardini E, O'Dell R, Chen M, Ra J, Georgelos J, Morehouse M, Melino K, Varma P, Toyonaga T, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET. American Journal Of Geriatric Psychiatry 2023, 32: 17-28. PMID: 37673749, PMCID: PMC10840732, DOI: 10.1016/j.jagp.2023.08.002.Peer-Reviewed Original ResearchSynaptic densityAlzheimer's diseaseMean diffusivitySynaptic lossGray matter microstructureGray matter mean diffusivityDisease pathologyHippocampal synaptic densityMajor pathological correlateSetting of ADAD-related neuropathologySynaptic vesicle glycoprotein 2AHippocampal mean diffusivityAlzheimer's disease pathologyAmyloid-positive participantsMatter mean diffusivityPositron emission tomography (PET) imagingEmission Tomography ImagingGray matter structuresPathological correlatesPositive participantsInverse associationAD groupCognitive impairmentDiseasePrincipal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patternsDisease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials
Van Dyck C, O'Dell R, Mecca A. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12388. PMID: 37187779, PMCID: PMC10175943, DOI: 10.1002/trc2.12388.Peer-Reviewed Original Research
2021
Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
Datta D, Leslie SN, Woo E, Amancharla N, Elmansy A, Lepe M, Mecca AP, Slusher BS, Nairn AC, Arnsten AFT. Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance. Frontiers In Aging Neuroscience 2021, 13: 760270. PMID: 34867287, PMCID: PMC8634091, DOI: 10.3389/fnagi.2021.760270.Peer-Reviewed Original ResearchCognitive disordersRat medial PFCMedial PFCGCPII inhibitorsPFC cognitive deficitsPrefrontal cortical activationGlutamate carboxypeptidase IIGCPII proteinMGluR3 expressionLocal infusionSystemic administrationAged ratsGCPII inhibitionMemory performancePrefrontal cortex impairsCortical activationCognitive impairmentCognitive deficitsInflammationGenetic insultsCarboxypeptidase IIDisordersGCPIICurrent studyInhibitorsSynthesizing Multi-tracer PET Images for Alzheimer’s Disease Patients Using a 3D Unified Anatomy-Aware Cyclic Adversarial Network
Zhou B, Wang R, Chen M, Mecca A, O’Dell R, Van Dyck C, Carson R, Duncan J, Liu C. Synthesizing Multi-tracer PET Images for Alzheimer’s Disease Patients Using a 3D Unified Anatomy-Aware Cyclic Adversarial Network. Lecture Notes In Computer Science 2021, 12906: 34-43. DOI: 10.1007/978-3-030-87231-1_4.Peer-Reviewed Case Reports and Technical NotesGeneration of synthetic PET images of synaptic density and amyloid from 18F‐FDG images using deep learning
Wang R, Liu H, Toyonaga T, Shi L, Wu J, Onofrey JA, Tsai Y, Naganawa M, Ma T, Liu Y, Chen M, Mecca AP, O’Dell R, van Dyck C, Carson RE, Liu C. Generation of synthetic PET images of synaptic density and amyloid from 18F‐FDG images using deep learning. Medical Physics 2021, 48: 5115-5129. PMID: 34224153, PMCID: PMC8455448, DOI: 10.1002/mp.15073.Peer-Reviewed Original ResearchPartial volume correction analysis for 11C-UCB-J PET studies of Alzheimer's disease
Lu Y, Toyonaga T, Naganawa M, Gallezot JD, Chen MK, Mecca AP, van Dyck CH, Carson RE. Partial volume correction analysis for 11C-UCB-J PET studies of Alzheimer's disease. NeuroImage 2021, 238: 118248. PMID: 34119639, PMCID: PMC8454285, DOI: 10.1016/j.neuroimage.2021.118248.Peer-Reviewed Original Research