2021
Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [18F]FPEB PET
Mecca AP, Rogers K, Jacobs Z, McDonald JW, Michalak HR, DellaGioia N, Zhao W, Hillmer AT, Nabulsi N, Lim K, Ropchan J, Huang Y, Matuskey D, Esterlis I, Carson RE, van Dyck CH. Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [18F]FPEB PET. NeuroImage 2021, 238: 118217. PMID: 34052464, PMCID: PMC8378132, DOI: 10.1016/j.neuroimage.2021.118217.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAgingBrain ChemistryFemaleFluorine RadioisotopesFluorodeoxyglucose F18Gray MatterHippocampusHumansMagnetic Resonance ImagingMaleMiddle AgedNeuroimagingOrgan SizePositron-Emission TomographyRadiopharmaceuticalsReceptor, Metabotropic Glutamate 5Young AdultConceptsMetabotropic glutamate receptor subtype 5MGluR5 availabilityMultiple brain regionsTissue lossSubtype 5Association cortexPrimary analysisBrain regionsAge-related molecular changesBrain glutamatergic systemBrain tissue lossNon-significant trendPartial volume correctionPositron emission tomographyBrain mGluR5Effect of ageAge-related declineGlutamatergic systemInverse associationTissue alterationsDistribution volumeEmission tomographyOlder ageCognitive functionExploratory analysisIdentifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis
Fang XT, Toyonaga T, Hillmer AT, Matuskey D, Holmes SE, Radhakrishnan R, Mecca AP, van Dyck CH, D’Souza D, Esterlis I, Worhunsky PD, Carson RE. Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis. NeuroImage 2021, 237: 118167. PMID: 34000404, PMCID: PMC8452380, DOI: 10.1016/j.neuroimage.2021.118167.Peer-Reviewed Original ResearchConceptsSynaptic densityResting-state functional magnetic resonance imagingSynaptic vesicle protein 2ALevel-dependent signal fluctuationsBrain networksFunctional magnetic resonance imagingMagnetic resonance imagingAge-related changesHealthy controlsResonance imagingRs-fMRIEffects of sexProtein 2AMultiple comparisonsHuman brainAgePotential utilitySexFirst evidenceCovariance patternsComparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study
Chen MK, Mecca AP, Naganawa M, Gallezot JD, Toyonaga T, Mondal J, Finnema SJ, Lin SF, O’Dell R, McDonald JW, Michalak HR, Vander Wyk B, Nabulsi NB, Huang Y, Arnsten AF, van Dyck CH, Carson RE. Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study. Cerebrovascular And Brain Metabolism Reviews 2021, 41: 2395-2409. PMID: 33757318, PMCID: PMC8393289, DOI: 10.1177/0271678x211004312.Peer-Reviewed Original ResearchConceptsSynaptic densityMedial temporal regionsAlzheimer's diseaseNeocortical regionsTemporal regionsRelative outcome measuresMedial temporal lobeVivo PET imagingJ bindingOutcome measuresTemporal lobeMagnitude of reductionCN participantsBrain regionsAD participantsDiseasePET imagingConcordant reductionNormal participantsSynaptic vesiclesPerfusionMetabolismSuitable markerParticipantsSimilar pattern
2020
Simplified Quantification of 11C-UCB-J PET Evaluated in a Large Human Cohort
Naganawa M, Gallezot JD, Finnema SJ, Matuskey D, Mecca A, Nabulsi NB, Labaree D, Ropchan J, Malison RT, D'Souza DC, Esterlis I, Detyniecki K, van Dyck CH, Huang Y, Carson RE. Simplified Quantification of 11C-UCB-J PET Evaluated in a Large Human Cohort. Journal Of Nuclear Medicine 2020, 62: 418-421. PMID: 32646875, PMCID: PMC8049341, DOI: 10.2967/jnumed.120.243949.Peer-Reviewed Original ResearchIn vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET
Mecca AP, Chen M, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Nabulsi NB, Vander Wyk B, Varma P, Arnsten AFT, Huang Y, Carson RE, van Dyck C. In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET. Alzheimer's & Dementia 2020, 16: 974-982. PMID: 32400950, PMCID: PMC7383876, DOI: 10.1002/alz.12097.Peer-Reviewed Original ResearchConceptsWidespread synaptic lossEarly Alzheimer's diseaseSynaptic lossAlzheimer's diseaseSynaptic vesicle glycoprotein 2AGray matter volumeMajor structural correlatePositron emission tomography (PET) imagingEmission Tomography ImagingDistribution volume ratioCerebellar reference regionNeocortical brain regionsSynaptic densityAD progressionConsistent pathologyPotential therapyMatter volumePromising biomarkerCognitive impairmentCN participantsBrain regionsDiseaseTomography imagingNormal participantsStructural correlatesPET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
2019
Statin Use and Risk of Cognitive Decline in the ADNI Cohort
Kemp EC, Ebner MK, Ramanan S, Godek TA, Pugh EA, Bartlett HH, McDonald JW, Mecca MC, van Dyck CH, Mecca AP, Initiative T. Statin Use and Risk of Cognitive Decline in the ADNI Cohort. American Journal Of Geriatric Psychiatry 2019, 28: 507-517. PMID: 31806426, PMCID: PMC7170771, DOI: 10.1016/j.jagp.2019.11.003.Peer-Reviewed Original ResearchDevelopment and Validation of a Polypharmacy Knowledge Assessment Instrument
Thomas JM, Mecca MC, Niehoff KM, Mecca AP, Van Ness PH, Brienza R, Hyson A, Jeffery S. Development and Validation of a Polypharmacy Knowledge Assessment Instrument. American Journal Of Pharmaceutical Education 2019, 83: 6435. PMID: 31333246, PMCID: PMC6630871, DOI: 10.5688/ajpe6435.Peer-Reviewed Original ResearchConceptsNP residentsGeriatric primary careGroup differencesWilcoxon rank sum testKnowledge assessment instrumentInternal medicine residentsRank sum testPrimary careOverall group differencesAcceptable internal consistencyKruskal-Wallis testResponse rateGroup validityPharmacistsSum testDelphi processSix-item versionEducational interventionMedicine residentsResidents' knowledgeBrief instrumentPharmacy residentsPolypharmacyMean scoreAttendingsAssessing an Interprofessional Polypharmacy and Deprescribing Educational Intervention for Primary Care Post-graduate Trainees: a Quantitative and Qualitative Evaluation
Mecca MC, Thomas JM, Niehoff KM, Hyson A, Jeffery SM, Sellinger J, Mecca AP, Van Ness PH, Fried TR, Brienza R. Assessing an Interprofessional Polypharmacy and Deprescribing Educational Intervention for Primary Care Post-graduate Trainees: a Quantitative and Qualitative Evaluation. Journal Of General Internal Medicine 2019, 34: 1220-1227. PMID: 30972554, PMCID: PMC6614292, DOI: 10.1007/s11606-019-04932-9.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overCohort StudiesDeprescriptionsDrug-Related Side Effects and Adverse ReactionsFemaleFollow-Up StudiesHumansInternship and ResidencyMalePharmacy ResidenciesPolypharmacyPotentially Inappropriate Medication ListPrimary Health CareProspective StudiesQualitative ResearchVeteransConceptsComplex medication managementMedication managementCardiovascular medicationsInternal medicineOlder adultsOutpatient medication managementProspective cohort studyType of medicationPre-post knowledge testInternal comparison groupPrimary care trainingAdverse health effectsInappropriate medicationsCohort studyMain MeasuresWeIntervention groupPost-graduate traineesMedical appointmentsMedicationsControl groupIndividual appointmentsCare trainingNP residentsPolypharmacyClinical setting
2018
Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.Peer-Reviewed Original ResearchConceptsPositron emission tomographic imagingSynaptic vesicle glycoprotein 2ASynaptic densityAlzheimer's diseaseEmission tomographic imagingHigh-resolution PET scanningPET scanningCognitive impairmentDisease-modifying therapiesDisease-modifying treatmentsNormal participantsCross-sectional studyPittsburgh compound BMajor structural correlateAmnestic mild cognitive impairmentMagnetic resonance imagingMild cognitive impairmentJ PET imagingRestoration of synapsesSpecific bindingNeurologic evaluationSynaptic lossDisease stagePostmortem studiesOutcome measuresEffects of Normative Adjustments to the Montreal Cognitive Assessment
Pugh EA, Kemp EC, van Dyck CH, Mecca AP, Sharp ES, Initiative F. Effects of Normative Adjustments to the Montreal Cognitive Assessment. American Journal Of Geriatric Psychiatry 2018, 26: 1258-1267. PMID: 30314940, PMCID: PMC6779033, DOI: 10.1016/j.jagp.2018.09.009.Peer-Reviewed Original ResearchSleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort
Mecca AP, Michalak HR, McDonald JW, Kemp EC, Pugh EA, Becker ML, Mecca MC, van Dyck CH. Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort. Dementia And Geriatric Cognitive Disorders 2018, 45: 232-242. PMID: 29886490, PMCID: PMC6178799, DOI: 10.1159/000488671.Peer-Reviewed Original ResearchConceptsMild cognitive impairmentCognitive declineSleep disturbancesSubsequent cognitive declineExecutive functionGlobal cognitionCognitionMCI participantsCognitive impairmentNormal cognitionEarly mild cognitive impairmentClinical conversionLongitudinal cohort studyYears of ageDiagnostic conversionADNI cohortCohort studyAlzheimer's diseaseSecondary analysisMemoryParticipantsImpairmentDeclineAdultsIndividualsGuanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial
Barcelos NM, Van Ness PH, Wagner AF, MacAvoy MG, Mecca AP, Anderson GM, Trentalange M, Hawkins KA, Sano M, Arnsten AFT, van Dyck CH. Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial. Neurobiology Of Aging 2018, 70: 117-124. PMID: 30007160, PMCID: PMC6503670, DOI: 10.1016/j.neurobiolaging.2018.05.033.Peer-Reviewed Original ResearchConceptsDose of guanfacineQuality of lifeZ-scoreCognitive functionPrefrontal cognitive dysfunctionCommon adverse eventsPrimary outcome measureRandomized clinical trialsGlobal functionOlder participantsHealthy older participantsPrefrontal cognitive functionDry mouthAdverse eventsAgonist guanfacineClinical trialsGuanfacine treatmentCognitive dysfunctionMean changeOutcome measuresPlaceboGuanfacineOlder individualsWeeksDoseDelays in the Air or Ground Transfer of Patients for Endovascular Thrombectomy
Regenhardt RW, Mecca AP, Flavin SA, Boulouis G, Lauer A, Zachrison KS, Boomhower J, Patel AB, Hirsch JA, Schwamm LH, Leslie-Mazwi TM. Delays in the Air or Ground Transfer of Patients for Endovascular Thrombectomy. Stroke 2018, 49: 1419-1425. PMID: 29712881, PMCID: PMC5970980, DOI: 10.1161/strokeaha.118.020618.Peer-Reviewed Original ResearchConceptsEndovascular therapySpoke hospitalsTelestroke networkUnderwent endovascular therapyEndovascular thrombectomyHealth StrokeIschemic strokeClinical outcomesMedian delayHub hospitalInclusion criteriaTelestroke consultsMultivariable regressionTreatment opportunitiesPossible predictorsTreatment ratesPatientsHospitalDaytime transfersLong transfer timesNational Institute
2017
Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease
Mecca AP, Barcelos NM, Wang S, Brück A, Nabulsi N, Planeta-Wilson B, Nadelmann J, Benincasa AL, Ropchan J, Huang Y, Gelernter J, Van Ness PH, Carson RE, van Dyck CH. Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease. Neurobiology Of Aging 2017, 61: 207-214. PMID: 29111487, PMCID: PMC5722236, DOI: 10.1016/j.neurobiolaging.2017.09.027.Peer-Reviewed Original ResearchConceptsΒ-amyloid burdenMiddle-aged individualsAβ burdenEpisodic memory performanceCognitive declineGM fractionCortical β-amyloid burdenBrain magnetic resonance imagingFirst-degree family historyCortical Aβ burdenGray matter fractionNormal middle-aged individualsSubsequent cognitive declineMagnetic resonance imagingPositron emission tomographyAPOE ε3ε3Cortical AβCerebral amyloidosisAPOE genotypeFamily historyPreclinical ADMemory performanceNeuropsychological testingAlzheimer's diseaseGray matter
2014
Idiom Use in a Young Man with Schizophrenia and Prominent Sexual Delusions
Fineberg SK, Mecca A, Lerner BA, Hills OF, Corlett PR, Viron M. Idiom Use in a Young Man with Schizophrenia and Prominent Sexual Delusions. Harvard Review Of Psychiatry 2014, 22: 306-315. PMID: 25188734, DOI: 10.1097/hrp.0000000000000053.Peer-Reviewed Case Reports and Technical NotesThe angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke
Joseph JP, Mecca AP, Regenhardt RW, Bennion DM, Rodríguez V, Desland F, Patel NA, Pioquinto DJ, Unger T, Katovich MJ, Steckelings UM, Sumners C. The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke. Neuropharmacology 2014, 81: 134-141. PMID: 24508710, PMCID: PMC7472595, DOI: 10.1016/j.neuropharm.2014.01.044.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin II Type 2 Receptor BlockersAnimalsBrain InfarctionBrain IschemiaCD11b AntigenCerebrovascular CirculationCytokinesDisease Models, AnimalDose-Response Relationship, DrugEndothelin-1Glial Fibrillary Acidic ProteinImidazolesMaleNitric Oxide Synthase Type IIPeroxidasePyridinesRatsRats, Sprague-DawleyStrokeSulfonamidesThiophenesTime FactorsConceptsMiddle cerebral artery occlusionPost-stroke administrationEndothelin-1Neurological deficitsIschemic strokeCerebroprotective actionCerebral damageCerebral ischemiaAT2R agonistChemokine (C-C) motif ligand 2Inducible nitric oxide synthaseBeneficial effectsCerebral infarct sizeMCAO-induced increaseCerebral artery occlusionAnti-inflammatory effectsCerebral blood flowNitric oxide synthaseSelective AT2R agonistPotential therapeutic valueType 2 mRNAAT2R inhibitorArtery occlusionPeripheral administrationHemorrhagic stroke
2013
Centrally administered angiotensin‐(1–7) increases the survival of stroke‐prone spontaneously hypertensive rats
Regenhardt RW, Mecca AP, Desland F, Ritucci‐Chinni P, Ludin JA, Greenstein D, Banuelos C, Bizon JL, Reinhard MK, Sumners C. Centrally administered angiotensin‐(1–7) increases the survival of stroke‐prone spontaneously hypertensive rats. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2013, 99: 442-453. PMID: 24142453, PMCID: PMC7416533, DOI: 10.1113/expphysiol.2013.075242.Peer-Reviewed Original ResearchConceptsHaemorrhagic strokeHypertensive ratsMicroglial activationIschemic strokeNeurological statusTherapeutic targetBeneficial actionsInfusion of AngMas receptor blockerHigh sodium dietPotential new therapeutic targetAction of angiotensinNumber of microgliaMechanism of injuryNumber of hemorrhagesSerum corticosterone levelsActivation of angiotensinPotential therapeutic targetNew therapeutic targetsPotential beneficial actionsPotential beneficial roleDays of ageAng-(1-7) treatmentIntracerebral inflammationMicroglial numbersAnti-inflammatory effects of angiotensin-(1-7) in ischemic stroke
Regenhardt RW, Desland F, Mecca AP, Pioquinto DJ, Afzal A, Mocco J, Sumners C. Anti-inflammatory effects of angiotensin-(1-7) in ischemic stroke. Neuropharmacology 2013, 71: 154-163. PMID: 23583926, PMCID: PMC3664115, DOI: 10.1016/j.neuropharm.2013.03.025.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IAnimalsAnti-Inflammatory Agents, Non-SteroidalBrain IschemiaCells, CulturedCerebral CortexDisease Models, AnimalGene Expression RegulationMaleMiceMice, Inbred StrainsMice, KnockoutMicrogliaNerve Tissue ProteinsNeuroprotective AgentsNitric OxideNitric Oxide Synthase Type IIPeptide FragmentsProto-Oncogene MasProto-Oncogene ProteinsRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledSpecific Pathogen-Free OrganismsStrokeConceptsInducible nitric oxide synthaseAnti-inflammatory effectsIschemic strokeEndothelin-1Cerebral cortexMiddle cerebral artery occlusionCerebral infarct sizeDifferentiation molecule 11bIntracerebral inflammatory responseCerebral artery occlusionAnti-inflammatory actionLipopolysaccharide-induced increasePro-inflammatory cytokinesCerebral blood flowINOS protein expressionNitric oxide synthaseNitric oxide productionNitric oxide generationExpression of mRNAAng-(1-7) treatmentSignificant cerebroprotectionCerebral vasoconstrictionArtery occlusionCerebroprotective actionReceptor MasUtilizing a cranial window to visualize the middle cerebral artery during endothelin-1 induced middle cerebral artery occlusion.
Regenhardt RW, Ansari S, Azari H, Caldwell KJ, Mecca AP. Utilizing a cranial window to visualize the middle cerebral artery during endothelin-1 induced middle cerebral artery occlusion. Journal Of Visualized Experiments 2013, e50015. PMID: 23463164, PMCID: PMC3605805, DOI: 10.3791/50015.Peer-Reviewed Original ResearchConceptsCranial windowEndothelin-1Cerebral arteryBrain parenchymaMiddle cerebral artery occlusion modelMiddle cerebral artery occlusionCerebral artery occlusionArtery occlusion modelMiddle cerebral arteryArtery occlusionIschemic strokeVasoconstricting peptideOcclusion modelVisualized vesselsLateral aspectTemporal boneArteryProximal portionRat cerebrumDuraVessel diameterCortical surfaceMCAOParietal boneParenchyma