2025
Elevated serum leucine levels are associated with cognitive impairment and reduced gray matter and cerebral volume across the Alzheimer’s disease continuum
Nasiri H, Azargoonjahromi A, Nouri Z, Azimi S, Zand H, Shourideh A, Heydari S, Mahmoudvand B, Barabadi S, Samadpour N, Mohamadhosseini A, Khodadadi A, Shakeri S, Mayeli M, Initiative F. Elevated serum leucine levels are associated with cognitive impairment and reduced gray matter and cerebral volume across the Alzheimer’s disease continuum. Neuroscience 2025, 577: 47-53. PMID: 40348165, DOI: 10.1016/j.neuroscience.2025.05.013.Peer-Reviewed Original ResearchConceptsCognitive performanceBrain volumeMediation analysisAlzheimer's Disease Assessment Scale-cognitive subscaleReduced gray matterGray matter volumeStructural brain volumesAssociated with cognitive impairmentAlzheimer's diseaseGray matterMagnetic resonance imagingPoor cognitive outcomesAlzheimer's disease continuumMatter volumeT1-weighted magnetic resonance imagingBrain structuresCognitive outcomesCerebral volumeCognitive impairmentCognitive declineBrain atrophyAD continuumBrainSerum leucine levelsAD pathology
2024
Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy
Barisano G, Iv M, Choupan J, Hayden-Gephart M, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Shaw L, Liu E, Montine T, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Jiminez G, Harvey D, Donohue M, Bernstein M, Fox N, Thompson P, Schuff N, DeCarli C, Borowski B, Gunter J, Senjem M, Vemuri P, Jones D, Kantarci K, Ward C, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Landau S, Cairns N, Householder E, Reinwald L, Lee V, Korecka M, Figurski M, Crawford K, Neu S, Foroud T, Potkin S, Shen L, Kelley F, Kim S, Nho K, Kachaturian Z, Frank R, Snyder P, Molchan S, Kaye J, Quinn J, Lind B, Carter R, Dolen S, Schneider L, Pawluczyk S, Beccera M, Teodoro L, Spann B, Brewer J, Vanderswag H, Fleisher A, Heidebrink J, Lord J, Petersen R, Mason S, Albers C, Knopman D, Johnson K, Doody R, Meyer J, Chowdhury M, Rountree S, Dang M, Stern Y, Honig L, Bell K, Ances B, Morris J, Carroll M, Leon S, Householder E, Mintun M, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geld-macher D, Brockington J, Roberson E, Grossman H, Mitsis E, deToledo-Morrell L, Shah R, Duara R, Varon D, Greig M, Roberts P, Albert M, Onyike C, D’Agostino D, Kielb S, Galvin J, Pogorelec D, Cerbone B, Michel C, Rusinek H, de Leon M, Glodzik L, De Santi S, Doraiswamy P, Petrella J, Wong T, Arnold S, Karlawish J, Wolk D, Smith C, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Lopez O, Oakley M, Simpson D, Porsteinsson A, Goldstein B, Martin K, Makino K, Ismail M, Brand C, Mulnard R, Thai G, Mc Adams Ortiz C, Womack K, Mathews D, Quiceno M, Arrastia R, King R, Weiner M, Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Swerdlow R, Apostolova L, Tingus K, Woo E, Silverman D, Lu P, Bartzokis G, Radford N, Parfitt F, Kendall T, Johnson H, Farlow M, Hake A, Matthews B, Herring S, Hunt C, van Dyck C, Carson R, MacAvoy M, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung G, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam M, Lipowski K, Wu C, Johnson N, Sadowsky C, Martinez W, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Johnson K, Marshall G, Frey M, Yesavage J, Taylor J, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Sirrel S, Kowall N, Killiany R, Budson A, Norbash A, Johnson P, Obisesan T, Wolday S, Allard J, Lerner A, Ogrocki P, Hudson L, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre D, Kataki M, Adeli A, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Santulli R, Kitzmiller T, Schwartz E, Sink K, Williamson J, Garg P, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J, Spicer K, Bachman D, Finger E, Pasternak S, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz S, Ponto L, Shim H, Smith K, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj B. Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy. EBioMedicine 2024, 111: 105523. PMID: 39721217, PMCID: PMC11732520, DOI: 10.1016/j.ebiom.2024.105523.Peer-Reviewed Original ResearchConceptsRisk of dementiaDementia riskAccelerated brain atrophyLower risk of dementiaMeasures of cognitive functionLongitudinal studyUS National Institutes of HealthNational Institutes of HealthCombat dementiaInstitutes of HealthPerivascular spaces countAlzheimer's disease biomarkersUS National InstitutesClinical measures of cognitive functioningDementiaBrain healthMixed-effects modelsScreening toolClinical measuresConfounding factorsObservational studyCognitive declineLongitudinal trajectoriesParticipantsBrain atrophySubject‐level Detection of Focal Neurodegeneration Using Spatiotemporal Connectomics: Towards Atrophy Characterization in Preclinical Alzheimer's Disease
Sánchez C, Diez I, Bueichekú E, Kim C, Grothe M, Sanchez‐Juan P, Sepulcre J. Subject‐level Detection of Focal Neurodegeneration Using Spatiotemporal Connectomics: Towards Atrophy Characterization in Preclinical Alzheimer's Disease. Alzheimer's & Dementia 2024, 20: e093803. PMCID: PMC11713922, DOI: 10.1002/alz.093803.Peer-Reviewed Original ResearchAlzheimer's diseaseNeurodegenerative diseasesGraph-theory-based frameworkHealthy agingBrain atrophyVoxel-based morphometryGray matter measuresAtrophy phenotypeSingle-subject levelPreclinical Alzheimer's diseaseCognitively normal participantsT1 MRI scansDisease phenotypePhenotypic heterogeneityBrain mechanismsGraph theory approachLongitudinal MRI dataFocal neurodegenerationNormal participantsAtrophy patternsFollow-up timepointsGroups of subjectsPhenotypePreclinical ADStructural similaritySubject‐level Detection of Focal Neurodegeneration Using Spatiotemporal Connectomics: Towards Atrophy Characterization in Preclinical Alzheimer’s Disease
Sánchez C, Diez I, Bueichekú E, Kim C, Grothe M, Sanchez‐Juan P, Sepulcre J. Subject‐level Detection of Focal Neurodegeneration Using Spatiotemporal Connectomics: Towards Atrophy Characterization in Preclinical Alzheimer’s Disease. Alzheimer's & Dementia 2024, 20: e089064. PMCID: PMC11715297, DOI: 10.1002/alz.089064.Peer-Reviewed Original ResearchAlzheimer's diseaseNeurodegenerative diseasesGraph-theory-based frameworkHealthy agingBrain atrophyVoxel-based morphometryGray matter measuresAtrophy phenotypeSingle-subject levelPreclinical Alzheimer's diseaseCognitively normal participantsT1 MRI scansDisease phenotypePhenotypic heterogeneityBrain mechanismsGraph theory approachLongitudinal MRI dataFocal neurodegenerationNormal participantsAtrophy patternsFollow-up timepointsGroups of subjectsPhenotypePreclinical ADStructural similarityOVERTURE Phase 2 Clinical Trial MRI Outcomes Demonstrate Consistent Treatment Benefits in Subgroup Analysis
Kern R, Kuang C, Seshagiri C, Konisky A, Galley A, Boasso A, Hempel E, Malchano Z, Vaughan B, Cimenser A, Da X, Shpokayte M, Hajos M. OVERTURE Phase 2 Clinical Trial MRI Outcomes Demonstrate Consistent Treatment Benefits in Subgroup Analysis. Alzheimer's & Dementia 2024, 20: e085091. PMCID: PMC11714597, DOI: 10.1002/alz.085091.Peer-Reviewed Original ResearchRandomized Controlled TrialsAPOE4 carrier statusBaseline subgroupsMild-moderate Alzheimer's diseasePhase 2 clinical trialIndicators of neurodegenerationBrain atrophyBrain volume outcomesBaseline ageBrain volume lossWhole brain volume lossCarrier statusWBVMagnetic resonance imagingAlzheimer's diseaseBaseline covariatesMonth 6Subgroup analysisAt-homeParticipantsClinical trialsTreatment outcomesActive treatmentOne-hourSham treatmentQuantifying White Matter Hyperintensity and Brain Volumes in Heterogeneous Clinical and Low-Field Portable MRI
Laso P, Cerri S, Sorby-Adams A, Guo J, Mateen F, Goebl P, Wu J, Liu P, Li H, Young S, Billot B, Puonti O, Sze G, Payabavash S, DeHavenon A, Sheth K, Rosen M, Kirsch J, Strisciuglio N, Wolterink J, Eshaghi A, Barkhof F, Kimberly W, Iglesias J. Quantifying White Matter Hyperintensity and Brain Volumes in Heterogeneous Clinical and Low-Field Portable MRI. 2024, 00: 1-5. DOI: 10.1109/isbi56570.2024.10635502.Peer-Reviewed Original ResearchMediation of Age and Thrombectomy Outcome by Neuroimaging Markers of Frailty in Patients With Stroke
Benali F, Singh N, Fladt J, Jaroenngarmsamer T, Bala F, Ospel J, Buck B, Dowlatshahi D, Field T, Hanel R, Peeling L, Tymianski M, Hill M, Goyal M, Ganesh A, Barber P, Smith E, Bal S, Subramanian S, Peters S, Couillard P, Klein G, Stys P, Coutts S, Wong J, Mitha A, Eesa M, Morrish W, Alqatani S, Kashani N, Venkatesan P, Teleg E, Sitaram A, Graham B, Gaal S, Moussaddy A, Chakraborty D, Maraj N, Lockey A, Chen S, Singh R, Alsultan A, Asunsian R, Tse D, Doshi D, Volny O, Ojha P, Wadhwa A, Marko M, Singh N, Wasyliw S, Ryckborst K, Kenney C, Save S, Jambula A, Newcommon N, Hull G, Blackstock D, Kiszczak S, Zimmel L, Wright M, Jahraus C, Andersen L, Bohn S, Paul J, Buck B, Butcher K, Shuaib A, Jeerakathil T, Jickling G, Emery D, Rempel J, Ower R, Ashforth R, Yeo T, Kotylak T, O;Kelly C, Chow M, Siddiqui M, Saqqur M, D'Souza A, Lloret M, Butt A, Nomani A, Kalashyan H, Thirunavukkarasu S, Jabs J, Fairall P, Piquette L, Phillips S, Green A, Gubitz G, Heidenreich J, Huynh T, Shankar J, Maloney W, Vandorpe R, Schmidt M, Pickett G, Weeks A, Jarrett J, MacDonald D, Arsenault J, Kinnear R, Mandzia J, Mayich M, Boulton M, Bullrich M, Fridman S, Kiwan R, Lee D, Lownie S, Khaw A, Pandey S, Sharma M, Sposato L, Wade K, Beauchamp B, Lambourn L, Amato-Marziali B, Roy D, Deneault N, Deschaintre Y, Gioia L, Jacquin G, Odier C, Stapf C, Iancu D, Raymond J, Weill A, Lapierre M, Jadil N, Jolteus J, Teitelbaum J, Angle M, Hannouche M, Badawy M, Letourneau J, Cortes M, Linnell G, Tampieri D, Vieira L, Legault C, Durcan L, Moore A, Cole E, Magnussen C, Salmon K, Khalil S, Desloges I, Waxman L, Abdon W, Lai S, Dowlatshahi D, Shamy M, Stotts G, Blacquiere D, Lesiuk H, Quateen A, Drake B, Dewar B, Daham Z, Kelly M, Hunter G, Peeling L, Graham B, Whelan R, Garner A, Urroz L, Maley S, Silver F, Casaubon L, Pikula A, Campo M, Schaafsma J, Jaigobin C, Krings T, Pereira V, Agid R, Farb R, Kalman L, Cayley A, Williams J, Stewart T, Misquitta K, Bharatha A, Selchen D, Marotta T, Sarma D, Montanera W, Spears J, Saposnik G, Kostyrko P, Li Y, Parra-Farinas C, Diestro J, Camden M, Verreault S, Mackey A, Audet M, Milot G, Lavoie P, Gariépy J, Collard K, Haché A, Sahlas D, Alshanbari A, Baldwin J, Catanese L, Chen B, Sa Boasquevisque D, Deshmukh A, Knapman J, Lamers S, Larrazabal R, MacMillan S, Mai L, Mattai A, Nayar S, Ng K, Oczkowski W, Perera K, Shawawrah M, Shoamanesh A, Sobhi G, Syed N, Yaher N, Vandervelde C, Wang D, Field T, Van Gaal S, Teal P, Benavente O, Wilson L, Mann S, Yip S, Murphy C, Heran M, Rohr A, Settecase F, Redekop G, Haw C, Maclean G, Murray K, Chiu R, Flexman A, Strecha E, Gayton Y, Yip J, Swartz R, Boulos M, Gladstone D, Yu A, Hopyan J, Khosravani H, Manosalva Alzate H, Southwell A, Kamra M, Lopes K, Kapoor A, da Costa L, Yang V, Dyer E, Shah R, Knowles B, Nichols J, Patterson J, Cope K, Dickerson L, Barton K, Gray K, Massengale T, Miller M, Simpson C, Walker S, Tennyson-Yemm C, Frei D, Bellon R, Atchie B, Kaminsky I, Wilson D, Schraeder N, Arias E, Kodis L, Talley M, Edinger A, Talley T, Dempsey I, Williams L, Williams S, Kupniewski S, Fasbinder B, Snead J, Choe H, Mackenzie L, Weisman D, Kozak O, Shah Q, Gzesh D, Kulandaivel K, Khoury J, Klein B, Bussinger P, Griffin L, DePalmo A, Oliva C, Jadhav A, Jovin T, Kenmuir C, Jankowitz B, Gross B, Rocha M, Starr M, Brown M, Hawkes C, Shah K, Tememe D, Walker G, Patel P, Klein B, Ziayee H, Limaye K, Baxendell L, Glichrist V, Feineigle P, Toseki Haibach K, Van Every C, Desai S, Zulfiqar M, Gibson L, Barrett S, Turkel-Parrella D, Arcot K, DiCrescento S, Farkas J, Filipowski G, Frontera J, Joset D, Liff J, Scher E, McDougall C, Kelly C, Patel A, Monteith S, Starkman S, Atchaneeyasakul K, Burgos A, Anne Y. Chua J, Gaines N, Grunberg I, Guzy J, Liu Z, Maluste N, Ramirez L, Sharma L, Heck D, Brown M, McDonald C, Calderon M, Hargis M, Roels C, Emmady P, Alvi T, Jayaraman M, Cutting S, Smith W, Foley S, Paolucci G, Haas R, Quinn K, Fuller L, Brierley R, Watkins C, Demir N, Lopez G, Vargas A, Osteraas N, Holtz B, Sauvageau E, Aghaebrahim A, Chmayssani M, Naval N, Day J, Dellorso S, Ludwig B, Schemmel D, Ebreo N, Bell K, Lewis L, Delucia M, Haussen D, Frankel M, Bhatt N, Bianchi N, Anderson A, Belagaje S, Liberato B, Rangaraju S, Al-Bayati A, Grossber J, Craft L, Schindler K, Schaad E, Schultz M, Sutherly L, Doppelheuer S, Charlton J, Faggard J, Barbret Z, DukSoo Han E, Walters R, Dolia J, El-Jamal S, Eby B, Saleem Y, Pearl H, Patel K, Rahman H, Butt R, English S, Puri A, Howk M, Singh J, Massari F, DeMacedo Rodrigues K, Kuhn A, English J, Barazangi N, Telischak N, Kim W, Ross J, DeVole N, Redford J, Ferreira M, Ponting K, Shen H, Bedenk A, Patel S, Fernandess J, Ke M, Spokoyny I, Gao B, Tong D, Chen C, Wong C, Choe J, Martin C, Summers D, Boutwell C, Olds K, Crandall S, Eatman J, Akhtar N, Holloway W, Halpin J, Donegan B, Schindler J, Hwang D, Gilmore E, Petersen N, Sheth K, Brown S, Beekman R, George B, Kaddouh F, Falcone G, Wira C, Matouk C, Loomis C, Amin H, Stretz H, Narula R, Jasne A, Sansing L, Agarwal T, Jasak S, Fontaine B, King Z, Kouhn L, Orgass H, Leary M, Nye J, Halbert K, Nystrom K, Neuschatz K, Petrucci D, Coppola A, Joyce T, Hou S, Umekubo M, Nakamura C, Ovando R, Zuniga D, Nien Y, Basto F, Arch A, Jong L, Conrad W, Abbott T, Yao J, Caganap S, Jordan J, Teitelbaum G, Darflinger R, Kelly D, Gupta R, Budzik R, Czerniak J, Groezinger K, Hicks W, Kaskar O, Katz B, Loochtan A, Pema P, Rai V, Vora N, Brown A, Goodman D, Danenbergs B, Gossett M, Bang O, Chung J, Jeon P, Kim K, Lim Y, Hoe Heo J, Nam H, Kim Y, Park H, Hwang I, Ha W, Choi J, Jeong K, Rha J, Park H, Yoon C, Kim B, Sohn S, Kim C, Yoo J, Hong J, Park H, Kim S, Choi M, Bae H, Lee J, Lee J, Jun G, Jeon S, Campbell B, Mitchell P, Yassi N, Davis S, Donnan G, Parsons M, Yan B, Dowling R, Bush S, Wu T, Shan D, Zhao H, Salvaris P, Alemseged F, Ng F, Williams C, Balabanski A, dos Santos A, Ng J, McDonald A, Jackson D, Tsoleridis J, Pesavento L, Kleinig T, Drew R, Cranefield J, Scroop R, Cagi L, Harvey J, Waters M, Thornton J, Brennan R, O'Hare A, Power S, Williams D, Boyle K, Moynihan B, Liddy A, Large M, Cullen A, Walsh R, Martin E, Lynch J, McElroy S, Murphy S, Coveney S, Deegan C, Horgan G, Kelly P, Laffan A, Llamas-Osorio Y, Lynch C, Mac Mahon P, Marnane M, McCabe J, Burns P, Tauro S, Cuddy S, Rennie I, Smyth G, Flynn P, Wiggam I, Kerr E, Gordon P, Fearon P, Roberts G, Patterson C, Adams K, Wells B, McFarland M, Moreira T, Sjöstrand C, Mazya M, Almqvist H, Wahlgren N, Steinberg A, Cooray C, Eriksson E, Thorén M, Keselman B, Ahmed N, Holmberg Å, Axelsson M, Berglund A, Golsari A, Hoppe J, Deb-Chatterji M, Cheng B, Barow E, Schlemm E, Lettow I, Jensen M, Otto D, Jaramillo K, Appelbohm H, Fiehler J, Bester M, Schönfeld M, Brekenfeld C, Holst B, Wortmann G, Koch F, Gerber J, Abramyuk A, Kaiser D, Winzer S, Prakapenia A, Pallesen L, Siepmann T, Barlinn K, Haase K, Sauer A, Psychogios M, Liman J, Brehm A, Maus V, Hollstein N, Reinke A, Neitz G, Schnieder M, Schwarz M, Ibrahim A, Müller J, Meister S, Bäumle B, Chapot R, Pilgram-Pastor S, Wallocha M, Stauder M, Celik E, Stracke P, Müller N, Weber R, Veltkamp R, Nagel S, Ringleb P, Heyse M, Amiri H, Mundiyanapurath S, Chen M, Beyrle E, Beck P, Möhlenbruch M. Mediation of Age and Thrombectomy Outcome by Neuroimaging Markers of Frailty in Patients With Stroke. JAMA Network Open 2024, 7: e2349628. PMID: 38165676, PMCID: PMC10762575, DOI: 10.1001/jamanetworkopen.2023.49628.Peer-Reviewed Original ResearchConceptsMarker of frailtyEndovascular thrombectomyAlteplase treatmentCohort studyESCAPE-NA1 trialAcute ischemic strokeEarly ischemic changesSmall vessel diseaseBest medical managementAcute care hospitalsBrain frailtyFrailty featuresIschemic strokeStroke severityBrain atrophyCare hospitalIschemic changesPrimary outcomeClinical featuresMedical managementPuncture timeThrombectomy outcomesPoor outcomeVessel diseaseFunctional outcomeSynaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling
Zhang D, Ruan J, Peng S, Li J, Hu X, Zhang Y, Zhang T, Ge Y, Zhu Z, Xiao X, Zhu Y, Li X, Li T, Zhou L, Gao Q, Zheng G, Zhao B, Li X, Zhu Y, Wu J, Li W, Zhao J, Ge W, Xu T, Jia J. Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling. Nature Neuroscience 2024, 27: 232-248. PMID: 38168932, PMCID: PMC10849963, DOI: 10.1038/s41593-023-01515-0.Peer-Reviewed Original ResearchConceptsArteriolar smooth muscle cellsSmooth muscle cellsNeurovascular couplingPrevent Ca2+ overloadMuscle cellsNMDA receptor subunit 1Cerebral neurovascular couplingCa2+ overloadMouse cerebral cortexGluN1 subunitGlutamatergic axonsArteriolar constrictionSpreading depolarizationCerebral ischemiaCell-type specificityFunctional hyperemiaCerebral cortexPostsynaptic dendritesBrain atrophyCell junctionsArteriolesBrain functionAxonsBrainCells
2023
Number of completed exercise sessions is associated with slower brain atrophy in MCI over 12 months in the EXERT trial
Digma L, Aslanyan V, Brewer J, Bevins E, Katula J, Chmelo E, Hodge H, LaCroix A, Shadyab A, Jacobs D, Salmon D, Feldman H, Pa J, Baker L. Number of completed exercise sessions is associated with slower brain atrophy in MCI over 12 months in the EXERT trial. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079285.Peer-Reviewed Original ResearchSupervised exercise sessionsBrain atrophyExercise sessionsAlzheimer's Disease Cooperative StudyLess brain atrophySupervised exercise interventionLower dementia riskLate-life exerciseAmount of exerciseInferior lateral ventricleExercise armExercise interventionDementia riskBaseline ageCDR-SBAerobic trainingLateral ventricleHigh adherenceIntervention adherenceNumber of sessionsVentricular expansionExercise typePlasma Aβ42/40Amnestic MCICognitive declineSensory‐Evoked 40Hz Gamma Oscillation: A Feasible and Promising Treatment Option for Alzheimer’s Disease
Hajos M, Boasso A, Cimenser A, Shpokayte M, Hempel E, Da X, Seshagiri C, Megerian J, Vaughan B, Malchano Z. Sensory‐Evoked 40Hz Gamma Oscillation: A Feasible and Promising Treatment Option for Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.072957.Peer-Reviewed Original ResearchClinical trialsAlzheimer's diseaseActive armPotential novel therapeutic interventionsSensory stimulationOccipital cortical thicknessAmyloid plaque loadAbnormal neuronal activityPivotal clinical trialsStimulation systemPromising treatment optionDifferent therapeutic approachesNovel therapeutic interventionsMinimal side effectsQuantitative MRI analysisNeuronal network oscillationsDaily therapyPlaque loadADCS-ADLBrain atrophyClinical presentationTreatment armsClinical benefitClinical efficacyAD pathologyComputational Image-Based Stroke Assessment for Evaluation of Cerebroprotectants with Longitudinal and Multi-Site Preclinical MRI
Cabeen R, Mandeville J, Hyder F, Sanganahalli B, Thedens D, Arbab A, Huang S, Bibic A, Tarakci E, Mihailovic J, Morais A, Lamb J, Nagarkatti K, Toga A, Lyden P, Ayata C. Computational Image-Based Stroke Assessment for Evaluation of Cerebroprotectants with Longitudinal and Multi-Site Preclinical MRI. 2023, 00: 1-5. DOI: 10.1109/isbi53787.2023.10230408.Peer-Reviewed Original ResearchMiddle cerebral artery occlusionData analytics approachManual annotationStroke assessmentRodent modelsCerebral artery occlusionData qualityCoronal MRI slicesPotential therapeutic interventionsMRI slicesNetworkAssessment NetworkOutcome quantificationInfarct volumeArtery occlusionIschemic strokeStroke outcomeBrain atrophyMidline shiftMRI dataLeading causeRodent preclinical studiesStroke expertsPreclinical studiesLesion extent
2022
Gamma‐Frequency Sensory Stimulation is Safe and Well‐Tolerated Treatment Option for Patients with Alzheimer’s Disease
Hajos M, Boasso A, Hempel E, Cimenser A, Seshagiri C, Megerian J, Vaughan B, Malchano Z. Gamma‐Frequency Sensory Stimulation is Safe and Well‐Tolerated Treatment Option for Patients with Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.064296.Peer-Reviewed Original ResearchTreatment-related adverse eventsAdverse eventsMagnetic resonance imagingSensory stimulationBrain atrophyTreatment optionsTreatment groupsDisease pathologyOpen-label extensionActive treatment groupHigher adherence ratesMultiple clinical trialsViable treatment optionAlzheimer's disease pathologyDays of treatmentSafety populationDaily therapyMethods PatientsNeurological examClinical presentationSham groupAdherence ratesClinical trialsTreatment periodLabel extensionExtra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial
Kaddoumi A, Denney T, Deshpande G, Robinson J, Beyers R, Redden D, Praticò D, Kyriakides T, Lu B, Kirby A, Beck D, Merner N. Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial. Nutrients 2022, 14: 5102. PMID: 36501136, PMCID: PMC9736478, DOI: 10.3390/nu14235102.Peer-Reviewed Original ResearchConceptsClinical Dementia RatingMild cognitive impairmentBBB permeabilityAlzheimer's diseaseProtective effectP-tau/t-tau ratioCognitive impairmentBlood-brain barrier breakdownBlood-brain barrier functionBrain connectivityBehavioral scoresAbnormal BBB permeabilityAD mouse modelClearance of AβT-tau ratioEarly Alzheimer's diseaseFunctional brain activationSecondary outcomesBrain atrophyControlled TrialsPrimary outcomePreclinical findingsBrain amyloidBlood biomarkersBarrier breakdownCoherent Activity in EEG Response to Gamma Sensory Stimulation Predicts Positive Outcome in Cognitive and Functional Abilities, and Brain Atrophy in Subjects with Alzheimer’s Disease (P4-6.004)
Cimenser A, Mrozak H, Da X, Travers T, Hempel E, Seshagiri C, Boasso A, Vaughan B, Megerian J, Malchano Z, Hajos M. Coherent Activity in EEG Response to Gamma Sensory Stimulation Predicts Positive Outcome in Cognitive and Functional Abilities, and Brain Atrophy in Subjects with Alzheimer’s Disease (P4-6.004). Neurology 2022, 98 DOI: 10.1212/wnl.98.18_supplement.1799.Peer-Reviewed Original ResearchCharacterizing Heterogeneity in Neuroimaging, Cognition, Clinical Symptoms, and Genetics Among Patients With Late-Life Depression
Wen J, Fu C, Tosun D, Veturi Y, Yang Z, Abdulkadir A, Mamourian E, Srinivasan D, Skampardoni I, Singh A, Nawani H, Bao J, Erus G, Shou H, Habes M, Doshi J, Varol E, Mackin R, Sotiras A, Fan Y, Saykin A, Sheline Y, Shen L, Ritchie M, Wolk D, Albert M, Resnick S, Davatzikos C, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Shaw L, Liu E, Montine T, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Jiminez G, Harvey D, Bernstein M, Fox N, Thompson P, Schuff N, DeCArli C, Borowski B, Gunter J, Senjem M, Vemuri P, Jones D, Kantarci K, Ward C, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Landau S, Cairns N, Reinwald L, Lee V, Korecka M, Figurski M, Crawford K, Neu S, Foroud T, Potkin S, Shen L, Kelley F, Kim S, Nho K, Kachaturian Z, Frank R, Snyder P, Molchan S, Kaye J, Quinn J, Lind B, Carter R, Dolen S, Schneider L, Pawluczyk S, Beccera M, Teodoro L, Spann B, Brewer J, Vanderswag H, Fleisher A, Heidebrink J, Lord J, Mason S, Albers C, Knopman D, Johnson K, Doody R, Meyer J, Chowdhury M, Rountree S, Dang M, Stern Y, Honig L, Bell K, Ances B, Morris J, Carroll M, Leon S, Householder E, Mintun M, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geldmacher D, Brockington J, Roberson E, Grossman H, Mitsis E, deToledo-Morrell L, Shah R, Duara R, Varon D, Greig M, Roberts P, Albert M, Onyike C, DAgostino II D, Kielb S, Galvin J, Pogorelec D, Cerbone B, Michel C, Rusinek H, Leon M, Glodzik L, Santi S, Doraiswamy P, Petrella J, Wong T, Arnold S, Karlawish J, Wolk D, Smith C, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Lopez O, Oakley M, Simpson D, Porsteinsson A, Goldstein B, Martin K, Makino K, Ismail M, Brand C, Mulnard R, Thai G, Ortiz C, Womack K, Mathews D, Quiceno M, Arrastia R, King R, Weiner M, Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Swerdlow R, Apostolova L, Tingus K, Woo E, Silverman D, Lu P, Bartzokis G, Radford N, Parfitt F, Kendall T, Johnson H, Farlow M, Hake A, Matthews B, Herring S, Hunt C, Dyck C, Carson R, MacAvoy M, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung G, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam M, Lipowski K, Wu C, Johnson N, Sadowsky C, Martinez W, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Johnson K, Marshall G, Frey M, Yesavage J, Taylor J, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Sirrel S, Kowall N, Killiany R, Budson A, Norbash A, Johnson P, Obisesan T, Wolday S, Allard J, Lerner A, Ogrocki P, Hudson L, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee T, Bartha D, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Reeder S, Bates V, Capote H, Rainka M, Scharre D, Kataki M, Adeli A, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Santulli R, Kitzmiller T, Schwartz E, Sink K, Williamson J, Garg P, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J, Spicer K, Bachman D, Finger E, Pasternak S, Rachinsky I, Drost D, Pomara N, Hernando R, Sarrael A, Schultz S, Ponto L, Shim H, Smith K, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj B. Characterizing Heterogeneity in Neuroimaging, Cognition, Clinical Symptoms, and Genetics Among Patients With Late-Life Depression. JAMA Psychiatry 2022, 79: 464-474. PMID: 35262657, PMCID: PMC8908227, DOI: 10.1001/jamapsychiatry.2022.0020.Peer-Reviewed Original ResearchConceptsLate-life depressionHealthy control individualsClinical symptomsSubset of individualsControl individualsGray matter brain volumeWidespread brain atrophyWhite matter fractional anisotropyMajor depressive disorderHigher depression severityGenetic profileBrain atrophyClinical outcomesClinical manifestationsDepressive disorderPossible disease mechanismsMAIN OUTCOMEBrain agingGeneral populationDepression severityMulticenter consortiumBrain volumeCognitive impairmentMulticenter sampleAlzheimer's disease
2021
Reduced brain atrophy by gamma sensory stimulation in Alzheimer’s disease patients
Hajos M, Megerian J, Hempel E, Vaughan B, Malchano Z. Reduced brain atrophy by gamma sensory stimulation in Alzheimer’s disease patients. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.057849.Peer-Reviewed Original ResearchWhole brain volume lossBrain volumetric changesBrain volume lossBrain atrophyDisease patientsAlzheimer's disease patientsSensory stimulationAD patientsLateral ventriclePotential disease-modifying effectsAge-matched healthy subjectsDisease-modifying effectsAccelerated brain atrophyTemporal lobe volumeMild AD patientsMild-moderate ADMR imaging analysisMethods PatientsClinical presentationSame therapySham groupPatient populationVolume lossHippocampal volumeHealthy subjectsFunctional Reserve: The Residual Variance in Instrumental Activities of Daily Living Not Explained by Brain Structure, Cognition, and Demographics
Kraal A, Massimo L, Fletcher E, Carrión C, Medina L, Mungas D, Gavett B, Farias S. Functional Reserve: The Residual Variance in Instrumental Activities of Daily Living Not Explained by Brain Structure, Cognition, and Demographics. Neuropsychology 2021, 35: 19-32. PMID: 33393797, PMCID: PMC8753970, DOI: 10.1037/neu0000705.Peer-Reviewed Original ResearchMeSH KeywordsActivities of Daily LivingAgedAged, 80 and overApathyBrainCognitionCognitive DysfunctionCognitive ReserveDementiaDemographyDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedNervous System DiseasesNeuropsychological TestsPsychiatric Status Rating ScalesConceptsBrain structuresDementia severityLate-life cognitive outcomesAssociation of cognitionModifiable intervention targetsInstrumental Activities of DailyCognitively normal individualsCognitive reserveCognitive performanceStructural equation modelingInstrumental activitiesActivities of DailyCognitive outcomesEnhanced functional reserveCognitive declineCognitionIntervention targetsBrain atrophyBrain pathologyLawton-Brody Instrumental ActivitiesOlder adultsEquation modelingPreliminary validationApathyLongitudinal data
2020
Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production
Chun H, Im H, Kang YJ, Kim Y, Shin JH, Won W, Lim J, Ju Y, Park YM, Kim S, Lee SE, Lee J, Woo J, Hwang Y, Cho H, Jo S, Park JH, Kim D, Kim DY, Seo JS, Gwag BJ, Kim YS, Park KD, Kaang BK, Cho H, Ryu H, Lee CJ. Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production. Nature Neuroscience 2020, 23: 1555-1566. PMID: 33199896, DOI: 10.1038/s41593-020-00735-y.Peer-Reviewed Original ResearchConceptsReactive astrocytesAlzheimer's diseaseAPP/PS1 micePathogenesis of ADReactivity of astrocytesBrains of patientsAppropriate experimental modelsGlial activationPS1 miceAstrocytic reactivityBrain atrophyPathological featuresNeuronal deathMonoamine oxidase BPathological hallmarkAD modelPrecise molecular mechanismsAnimal modelsAstrocytesCognitive impairmentPathological contributionExperimental modelDiseaseOxidase BEventual deathNemo-like kinase reduces mutant huntingtin levels and mitigates Huntington’s disease
Jiang M, Zhang X, Liu H, LeBron J, Alexandris A, Peng Q, Gu H, Yang F, Li Y, Wang R, Hou Z, Arbez N, Ren Q, Dong JL, Whela E, Wang R, Ratovitski T, Troncoso JC, Mori S, Ross CA, Lim J, Duan W. Nemo-like kinase reduces mutant huntingtin levels and mitigates Huntington’s disease. Human Molecular Genetics 2020, 29: 1340-1352. PMID: 32242231, PMCID: PMC7254850, DOI: 10.1093/hmg/ddaa061.Peer-Reviewed Original ResearchConceptsBrain atrophyHD miceNemo-like kinaseMHTT levelsHD mouse modelsNew molecular targetsHD human brainHuntingtin proteinEffect of NLKMouse striatal cellsFurther mechanistic studiesActivity-dependent mannerHTT protein levelsMouse modelAdult brainStriatal cellsProtective roleMutant Htt aggregationAmino acids 120Huntington's diseaseMutant huntingtin levelsMolecular targetsHuntingtin levelsProtein levelsBrain
2019
Regional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1
Labayru G, Diez I, Sepulcre J, Fernández E, Zulaica M, Cortés J, de Munain A, Sistiaga A. Regional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1. NeuroImage Clinical 2019, 24: 102078. PMID: 31795042, PMCID: PMC6861566, DOI: 10.1016/j.nicl.2019.102078.Peer-Reviewed Original ResearchConceptsGlobal gray matterDiffusion tensor imagingCTG expansion sizeSubcortical regionsWhite matter lesionsMyotonic dystrophy type 1Fractional anisotropyStructural brain signaturesBrain atrophyAssociated with cognitive impairmentStructural cerebral changesAssociation cortical regionsDegree of muscular impairmentMicrostructural WM abnormalitiesVoxel Based MorphometryWhite matterHealthy controlsDM1 patientsRegional brain atrophyType 1Global white matterIQ estimatesNeuropsychological profileGM reductionNeuropsychological scores
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