2025
Reduced removal of waste products from energy metabolism takes center stage in human brain aging
Mangia S, DiNuzzo M, Ponticorvo S, Dienel G, Behar K, Benveniste H, Hyder F, Giove F, Herculano-Houzel S, Petroff O, Eberly L, Filip P, Michaeli S, Rothman D. Reduced removal of waste products from energy metabolism takes center stage in human brain aging. Scientific Reports 2025, 15: 8127. PMID: 40057554, PMCID: PMC11890754, DOI: 10.1038/s41598-025-90342-3.Peer-Reviewed Original ResearchDeep learning to quantify the pace of brain aging in relation to neurocognitive changes
Yin C, Imms P, Chowdhury N, Chaudhari N, Ping H, Wang H, Bogdan P, Irimia A, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Landau S, Rivera-Mindt M, Okonkwo O, Shaw L, Lee E, Toga A, Beckett L, Harvey D, Green R, Saykin A, Nho K, Perrin R, Tosun D, Sachdev P, Green R, Drake E, Montine T, Conti C, Weiner M, Nosheny R, Truran Sacrey D, Fockler J, Miller M, Conti C, Kwang W, Jin C, Diaz A, Ashford M, Flenniken D, Kormos A, Petersen R, Aisen P, Rafii M, Raman R, Jimenez G, Donohue M, Salazar J, Fidell A, Boatwright V, Robison J, Zimmerman C, Cabrera Y, Walter S, Clanton T, Shaffer E, Webb C, Hergesheimer L, Smith S, Ogwang S, Adegoke O, Mahboubi P, Pizzola J, Jenkins C, Beckett L, Harvey D, Donohue M, Saito N, Diaz A, Hussen K, Okonkwo O, Rivera-Mindt M, Amaza H, Thao M, Parkins S, Ayo O, Glittenberg M, Hoang I, Germano K, Strong J, Weisensel T, Magana F, Thomas L, Guzman V, Ajayi A, Di Benedetto J, Talavera S, Jack C, Felmlee J, Fox N, Thompson P, DeCarli C, Forghanian-Arani A, Borowski B, Reyes C, Hedberg C, Ward C, Schwarz C, Reyes D, Gunter J, Moore-Weiss J, Kantarci K, Matoush L, Senjem M, Vemuri P, Reid R, Malone I, Thomopoulos S, Nir T, Jahanshad N, Knaack A, Fletcher E, Harvey D, Tosun-Turgut D, Rossi Chen S, Choe M, Crawford K, Yushkevich P, Das S, Jagust W, Landau S, Koeppe R, Rabinovici G, Villemagne V, LoPresti B, Perrin R, Morris J, Franklin E, Bernhardt H, Cairns N, Taylor-Reinwald L, Shaw L, Lee E, Lee V, Korecka M, Brylska M, Wan Y, Trojanowki J, Toga A, Crawford K, Neu S, Saykin A, Nho K, Foroud T, Jo T, Risacher S, Craft H, Apostolova L, Nudelman K, Faber K, Potter Z, Lacy K, Kaddurah-Daouk R, Shen L, Karlawish J, Erickson C, Grill J, Largent E, Harkins K, Weiner M, Thal L, Kachaturian Z, Frank R, Snyder P, Buckholtz N, Hsiao J, Ryan L, Molchan S, Khachaturian Z, Carrillo M, Potter W, Barnes L, Bernard M, González H, Ho C, Hsiao J, Jackson J, Masliah E, Masterman D, Okonkwo O, Perrin R, Ryan L, Silverberg N, Silbert L, Kaye J, White S, Pierce A, Thomas A, Clay T, Schwartz D, Devereux G, Taylor J, Ryan J, Nguyen M, DeCapo M, Shang Y, Schneider L, Munoz C, Ferman D, Conant C, Martin K, Oleary K, Pawluczyk S, Trejo E, Dagerman K, Teodoro L, Becerra M, Fairooz M, Garrison S, Boudreau J, Avila Y, Brewer J, Jacobson A, Gama A, Kim C, Little E, Frascino J, Ferng N, Trujillo S, Heidebrink J, Koeppe R, MacDonald S, Malyarenko D, Ziolkowski J, O’Connor J, Robert N, Lowe S, Rogers V, Petersen R, Hackenmiller B, Boeve B, Albers C, Kreuger C, Jones D, Knopman D, Botha H, Magnuson J, Graff-Radford J, Crawley K, Schumacher M, McKinzie S, Smith S, Helland T, Lowe V, Ramanan V, Pavlik V, Faircloth J, Bishop J, Nath J, Chaudhary M, Kataki M, Yu M, Pacini N, Barker R, Brooks R, Aggarwal R, Honig L, Stern Y, Mintz A, Cordona J, Hernandez M, Long J, Arnold A, Groves A, Middleton A, Vogler B, McCurry C, Mayo C, Raji C, Amtashar F, Klemp H, Elmore H, Ruszkiewicz J, Kusuran J, Stewart J, Horenkamp J, Greeson J, Wever K, Vo K, Larkin K, Rao L, Schoolcraft L, Gallagher L, Paczynski M, McMillan M, Holt M, Gagliano N, Henson R, LaBarge R, Swarm R, Munie S, Cepeda S, Winterton S, Hegedus S, Wilson T, Harte T, Bonacorsi Z, Geldmacher D, Watkins A, Barger B, Smelser B, Bates C, Stover C, McKinley E, Ikner G, Hendrix H, Cooper H, Mahaffey J, Booth Robbins L, Brown Ashley L, Natelson-Love M, Carter P, Solomon V, Grossman H, Groome A, Ardolino A, Kaplan A, Sheppard F, Burgos-Rivera G, Garcia-Camilo G, Lim J, Neugroschl J, Jackson K, Evans K, Soleimani L, Sano M, Ghesani N, Binder S, Apuango X, Sood A, Troutman A, Blanchard K, Richards A, Nelson G, Hendrickson K, Yurko E, Plenge J, Rufo V, Shah R, Duara R, Lynch B, Chirinos C, Dittrich C, Campbell D, Mejia D, Perez G, Colvee H, Gonzalez J, Gondrez J, Knaack J, Acevedo M, Cereijo M, Greig-Custo M, Villar M, Wishnia M, Detling S, Barker W, Albert M, Moghekar A, Rodzon B, Demsky C, Pontone G, Pekar J, Farrington L, Pomper M, Johnson N, Alo T, Sadowski M, Ulysse A, Masurkar A, Marti B, Mossa D, Geesey E, Petrocca E, Schulze E, Wong J, Boonsiri J, Kenowsky S, Martinez T, Briglall V, Doraiswamy P, Nwosu A, Adhikari A, Hellegers C, Petrella J, James O, Wong T, Hawk T, Vaishnavi S, McCoubrey H, Nasrallah I, Rovere R, Maneval J, Robinson E, Rivera F, Uffelman J, Combs M, O’Donnell P, Manning S, King R, Nieto A, Glueck A, Mandal A, Swain A, Gamble B, Meacham B, Forenback D, Ross D, Cheatham E, Hartman E, Cornell G, Harp J, Ashe L, Goins L, Watts L, Yazell M, Mandal P, Buckler R, Vincent S, Rudd T, Lopez O, Malia A, Chiado C, Zik C, Ruszkiewicz J, Savage K, Fenice L, Oakley M, Tacey P, Berman S, Bowser S, Hegedus S, Saganis X, Porsteinsson A, Mathewson A, Widman A, Holvey B, Clark E, Morales E, Young I, Ruszkiewicz J, Hopkins K, Martin K, Kowalski N, Hunt R, Calzavara R, Kurvach R, D’Ambrosio S, Thai G, Vides B, Lieb B, McAdams-Ortiz C, Toso C, Mares I, Moorlach K, Liu L, Corona M, Nguyen M, Tallakson M, McDonnell M, Rangel M, Basheer N, Place P, Romero R, Tam S, Nguyen T, Thomas A, Frolov A, Khera A, Browning A, Kelley B, Dawson C, Mathews D, Most E, Phillips E, Nguyen L, Nunez M, Miller M, Jones M, Martinez N, Logan R, McColl R, Pham S, Fox T, Moore T, Levey A, Brown A, Kippels A, Ellison A, Lyons C, Hales C, Parry C, Williams C, McCorkle E, Harris G, Rose H, Jooma I, Al-Amin J, Lah J, Webster J, Swiniarski J, Chapman L, Donnelly L, Mariotti L, Locke M, Vaughn P, Penn R, Carpentier S, Yeboah S, Basadre S, Malakauskas S, Lyron S, Villinger T, Burney T, Burns J, Abusalim A, Dahlgren A, Montero A, Arthur A, Dooly H, Kreszyn K, Berner K, Gillen L, Scanlan M, Madison M, Mathis N, Switzer P, Townley R, Fikru S, Sullivan S, Wright E, Beigi M, Daley A, Ko A, Luong B, Nyborg G, Morales J, Durbin K, Garcia L, Parand L, Macias L, Monserratt L, Farchi M, Wu P, Hernandez R, Rodriguez T, Graff-Radford N, Marolt A, Thomas A, Aloszka D, Moncayo E, Westerhold E, Day G, Chrestensen K, Imhansiemhonehi M, McKinzie S, Stephens S, Grant S, Brosch J, Perkins A, Saunders A, Kovac D, Polson H, Mwaura I, Mejia K, Britt K, King K, Nichols K, Lawrence K, Rankin L, Farlow M, Wiesenauer P, Bryant R, Herring S, Lynch S, Wilson S, Day T, Korst W, van Dyck C, Mecca A, Miller A, Brennan A, Khan A, Ruan A, Gunnoud C, Mendonca C, Raynes-Goldfinger D, Salardini E, Hidalgo E, Cooper E, Singh E, Murphy E, May J, Stanhope J, Lam J, Waszak J, Nelsen K, Sacaza K, Hasbani M, Donahue M, Chen M, Barcelos N, Eigenberger P, Bonomi R, O’Dell R, Jefferson S, Khasnavis S, Smilowitz S, DeStefano S, Good S, Camarro T, Clayton V, Cavrel Y, Lu Y, Chertkow H, Bergman H, Hosein C, Black S, Kapadia A, Bhan A, Lam B, Scott C, Gabriel G, Bray J, Zotovic L, Gutierrez M, Masellis M, Farshadi M, Gui M, Mitchell M, Taylor R, Endre R, Taghi-Zada Z, Hsiung R, English C, Kim E, Yau E, Tong H, Barlow L, Jennings L, Assaly M, Nunes P, Marian T, Kertesz A, Rogers J, Trost D, Wint D, Bernick C, Munic D, Grant I, Korkoyah A, Raja A, Lapins A, Ryan C, Pejic J, Basham K, Lukose L, Haddad L, Quinlan L, Houghtaling N, Sadowsky C, Martinez W, Villena T, Reynolds B, Forero A, Ward C, Brennan E, Figueroa E, Esposito G, Mallory J, Johnson K, Turner K, Seidenberg K, McCann K, Bassett M, Chadwick M, Turner R, Bean R, Sharma S, Marshall G, Haviari A, Pietras A, Wallace B, Munro C, Rivera-Delpin G, Hustead H, Levesque I, Ramirez J, Nolan K, Glennon K, Palou M, Erkkinen M, DaSilva N, Friedman P, Silver R, Salazar R, Polleys R, McGinnis S, Gale S, Hall T, Luu T, Chao S, Lin E, Coleman J, Epperson K, Vasanawala M, Atri A, Rangel A, Evans B, Monarrez C, Cline C, Liebsack C, Bandy D, Goldfarb D, Intorcia D, Olgin J, Clark K, King K, York K, Reade M, Callan M, Glass M, Johnson M, Gutierrez M, Goddard M, Trncic N, Choudhury P, Reyes P, Lowery S, Hall S, Olgin S, de Santiago S, Alosco M, Ton A, Jimenez A, Ellison A, Tran A, Anderson B, Carter D, Veronelli D, Lenio S, Steinberg E, Mez J, Weller J, Johns J, Mez J, Harkins J, Puleio A, Hoti I, Mwicigi J, Puleio A, Alosco M, Schultz O, Lauture M, Steinberg E, Denis R, Killiany R, Singh S, Lenio S, Qiu W, Devis Y, Obisesan T, Stone A, Ordor D, Udodong I, Okonkwo I, Khan J, Turner J, Hughes K, Kadiri O, Duffy C, Moss A, Stapleton K, Toth M, Sanders M, Ayres M, Hamski M, Fatica P, Ogrocki P, Ash S, Pot S, Chen D, Soto A, Tanase C, Bissig D, Vanya H, Russell H, Patel H, Zhang H, Wallace K, Ayers K, Gallegos M, Forloines M, Sinn M, Kahulugan Q, Isip R, Calderon S, Hamm T, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Perrin A, Tariot P, Fleisher A, Reeder S, Capote H, Emborsky A, Mattle A, Ajtai B, Wagner B, Myers B, Slazyk D, Fragale D, Fransen E, Macnamara H, Falletta J, Hirtreiter J, Mechtler L, King M, Asbach M, Rainka M, Zawislak R, Wisniewski S, O’Malley S, Jimenez-Knight T, Peehler T, Aladeen T, Bates V, Wenner V, Elmalik W, Scharre D, Ramamurthy A, Bouchachi S, Kataki M, Tarawneh R, Kelley B, Celmins D, Leader A, Figueroa C, Bauerle H, Patterson K, Reposa M, Presto S, Ahmed T, Stewart W, Pearlson G, Blank K, Anderson K, Santulli R, Schwartz E, Williamson J, Jessup A, Williams A, Duncan C, O’Connell A, Gagnon K, Zamora E, Bateman J, Crawford F, Thompson D, Walker E, Rowell J, White M, Ledford P, Bohlman S, Henkle S, Bottoms J, Moretz L, Hoover B, Shannon M, Rogers S, Baker W, Harrison W, Wu C, DeMarco A, Stipanovich A, Arcuri D, Clark J, Davis J, Doyon K, Amoyaw M, Acosta M, Bailey R, Warren S, Fogerty T, Sanborn V, Riddle M, Salloway S, Malloy P, Correia S, Windon C, Blackburn M, Rosen H, Miller B, Smith A, Mba I, Echevarria J, Janavs J, Roglaski E, Yong M, Devine R, Okhravi H, Rivera E, Kalowsky T, Smith C, Rosario C, Masdeu J, Le R, Gurung M, Sabbagh M, Garcia A, Ellis Slaughter M, Elayan N, Acothley S, Pomara N, Hernando R, Pomara V, Reichert C, Brawman-Mintzer O, Acree A, Williams A, Long C, Long R, Newhouse P, Hill S, Boegel A, Seshadri S, Saklad A, Jones F, Hu W, Sotelo V, Gonazalez Rojas Y, Mintzer J, Flynn Longmire C, Spicer K. Deep learning to quantify the pace of brain aging in relation to neurocognitive changes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2413442122. PMID: 39993207, PMCID: PMC11912385, DOI: 10.1073/pnas.2413442122.Peer-Reviewed Original ResearchConceptsCN adultsBrain agingNeuroanatomical agingLongitudinal modelAdverse cognitive changesChronological ageAlzheimer's diseaseNeurocognitive agingCognitive changesNeurocognitive changesCognitive functionNeurocognitive statusAssociated with changesAge trendsLongitudinal MRIAdultsBrainQuantify DNA methylationAD risk assessmentBlood-brain barrier
2024
Adolescent brain maturation associated with environmental factors: a multivariate analysis
Ray B, Jensen D, Suresh P, Thapaliya B, Sapkota R, Farahdel B, Fu Z, Chen J, Calhoun V, Liu J. Adolescent brain maturation associated with environmental factors: a multivariate analysis. Frontiers In Neuroimaging 2024, 3: 1390409. PMID: 39629197, PMCID: PMC11613425, DOI: 10.3389/fnimg.2024.1390409.Peer-Reviewed Original ResearchLeft medial orbitofrontal cortexReduced gray matter densityMedial orbitofrontal cortexMiddle temporal gyrusGray matter densityIncreased functional connectivityIncrease cognitive performanceSusceptible to environmental influencesBilateral occipital regionsDelayed brain maturationIncreased cortical thicknessOrbitofrontal cortexAdolescent brainHuman adolescentsTemporal gyrusBrain characteristicsCognitive performanceBrain regionsBrain age estimationBrain metricsFunctional connectivityBrain agingBrain maturationBrain variationBrain modalitiesCommon and unique brain aging patterns between females and males quantified by large‐scale deep learning
Du Y, Yuan Z, Sui J, Calhoun V. Common and unique brain aging patterns between females and males quantified by large‐scale deep learning. Human Brain Mapping 2024, 45: e70005. PMID: 39225381, PMCID: PMC11369911, DOI: 10.1002/hbm.70005.Peer-Reviewed Original ResearchConceptsBrain functional changesFunctional connectivityCognitive controlBrain agingBrain functionPatterns of brain agingResting-state brain functional connectivityBrain functional interactionsBrain functional connectivityHuman brain functionBrain aging patternsGender commonalitiesAge-related changesDeep learningHealthy participantsNormal agingNegative connectionFunctional changesBrainPositive connectionDeep learning modelsFunctional domainsAge effectsFunctional interactionsCross-validation schemeReplication and Refinement of Brain Age Model for Adolescent Development
Ray B, Chen J, Fu Z, Suresh P, Thapaliya B, Farahdel B, Calhoun V, Liu J. Replication and Refinement of Brain Age Model for Adolescent Development. 2024, 00: 1-5. DOI: 10.1109/isbi56570.2024.10635532.Peer-Reviewed Original ResearchBrain age modelAdolescent Brain Cognitive DevelopmentInformation processing speedBrain age gapABCD participantsBrain agingVerbal comprehension abilityEstimated brain ageEstimation of brain ageNeuropsychiatric problemsProcessing speedCognitive developmentAdolescent developmentAge gapComprehension abilityBrain developmentAge rangeBrainChronological ageAdolescentsParticipantsBaselineResting state electroencephalographic brain activity in neonates can predict age and is indicative of neurodevelopmental outcome
Ansari A, Pillay K, Arasteh E, Dereymaeker A, Mellado G, Jansen K, Winkler A, Naulaers G, Bhatt A, Van Huffel S, Hartley C, De Vos M, Slater R, Baxter L. Resting state electroencephalographic brain activity in neonates can predict age and is indicative of neurodevelopmental outcome. Clinical Neurophysiology 2024, 163: 226-235. PMID: 38797002, PMCID: PMC11250083, DOI: 10.1016/j.clinph.2024.05.002.Peer-Reviewed Original ResearchNeurodevelopmental outcomesResting state EEG dataBayley Scales of InfantAbnormal outcome groupsClinical sitesResting-state EEG activityPostmenstrual agePreterm neonatesOutcome groupNeonatesEEG activityBrain age gapElectroencephalographic brain activityBrain agingWeeksEEG dataGap magnitudeOutcomesBrainAgeIndependent datasetsPretermBSIDBrain activityInfantsRelative Brain Age Is Associated With Socioeconomic Status and Anxiety/Depression Problems in Youth
Cohen J, Ramphal B, DeSerisy M, Zhao Y, Pagliaccio D, Colcombe S, Milham M, Margolis A. Relative Brain Age Is Associated With Socioeconomic Status and Anxiety/Depression Problems in Youth. Developmental Psychology 2024, 60: 199-209. PMID: 37747510, PMCID: PMC10993304, DOI: 10.1037/dev0001593.Peer-Reviewed Original ResearchConceptsParental occupational prestigeParental psychiatric diagnosisBrain agingPsychiatric diagnosisPsychiatric riskPeriod of rapid neurodevelopmentSocioeconomic statusDevelopmental brain researchHealthy Brain NetworkDelay brain agingPsychiatric disordersPsychiatric symptomsOccupational prestigeAnxiety/depression problemsBrain networksPsychiatric illnessBrain structuresInfluence of socioeconomic statusAnxious/depressed scoresComponents of socioeconomic statusRapid neurodevelopmentAssociated with socioeconomic statusSocioeconomic status componentsMeasures of biological agingCovariance patterns
2023
Proteome Network Analysis Identifies Potential Biomarkers for Brain Aging
Short M, Fohner A, Skjellegrind H, Beiser A, Gonzales M, Satizabal C, Austin T, Longstreth W, Bis J, Lopez O, Hveem K, Selbæk G, Larson M, Yang Q, Aparicio H, McGrath E, Gerszten R, DeCarli C, Psaty B, Vasan R, Zare H, Seshadri S. Proteome Network Analysis Identifies Potential Biomarkers for Brain Aging. Journal Of Alzheimer's Disease 2023, 96: 1767-1780. PMID: 38007645, PMCID: PMC10741337, DOI: 10.3233/jad-230145.Peer-Reviewed Original ResearchConceptsCardiovascular Health StudyRisk of incident dementiaFramingham Heart StudyIncident dementiaIncident all-causeOffspring cohort participantsCommunity-based cohortCognitively healthy adultsAssociated with hippocampal volumeHealth StudyBrain volumeBrain agingBurden of comorbiditiesCohort participantsHeart StudyAll-causeAssociated with total brain volumeClinical dementiaDementiaTotal brain volumeAD dementiaModules of co-expressed proteinsOlder cohortMRI brain volumesWhite matter hyperintensitiesEvidence Accumulation Rate Moderates the Relationship between Enriched Environment Exposure and Age-Related Response Speed Declines
Brosnan M, Pearce D, O’Neill M, Loughnane G, Fleming B, Zhou S, Chong T, Nobre A, Connell R, Bellgrove M. Evidence Accumulation Rate Moderates the Relationship between Enriched Environment Exposure and Age-Related Response Speed Declines. Journal Of Neuroscience 2023, 43: 6401-6414. PMID: 37507230, PMCID: PMC10500991, DOI: 10.1523/jneurosci.2260-21.2023.Peer-Reviewed Original ResearchConceptsCognitive functionBrain healthOlder adultsNeural metricsTrajectories of cognitive agingMarkers of brain healthLevel of cognitive functioningEnriched environmentEvidence accumulation ratesPreservation of cognitive functionGlobal cognitive functionInfluence of EENeurocognitive vulnerabilityCognitive agingCognitive reserveMotor processesSensory evidenceBrain activityNeurocognitive healthEvidence accumulationResponse speedBrain agingAging brainSocial stimulationSpeed declineHow Does Aging Affect Whole-brain Functional Network Connectivity? Evidence from An ICA Method
Du Y, Guo Y, Calhoun V. How Does Aging Affect Whole-brain Functional Network Connectivity? Evidence from An ICA Method. Annual International Conference Of The IEEE Engineering In Medicine And Biology Society (EMBC) 2023, 00: 1-4. PMID: 38083384, DOI: 10.1109/embc40787.2023.10340189.Peer-Reviewed Original ResearchAging brain shows joint declines in brain within-network connectivity and between-network connectivity: a large-sample study (N > 6,000)
Du Y, Guo Y, Calhoun V. Aging brain shows joint declines in brain within-network connectivity and between-network connectivity: a large-sample study (N > 6,000). Frontiers In Aging Neuroscience 2023, 15: 1159054. PMID: 37273655, PMCID: PMC10233064, DOI: 10.3389/fnagi.2023.1159054.Peer-Reviewed Original ResearchFunctional network connectivityWithin-network connectivityCognitive control networkFunctional networksIncreased within-network connectivityDecreased within-network connectivityWhole-brain functional networksControl networkReduced functional network connectivityBetween-network connectivityWhole-brain levelNon-pathological agingSub-cortical networksIndependent component analysisBrain functional networksMode networkAging-related changesSensorimotor networkNeuroimaging dataConnectivity declineVisual networkWhole-brainBrain agingAging brainEffects of ageAnatomically interpretable deep learning of brain age captures domain-specific cognitive impairment
Yin C, Imms P, Cheng M, Amgalan A, Chowdhury N, Massett R, Chaudhari N, Chen X, Thompson P, Bogdan P, Irimia A, Initiative T, Weiner M, Aisen P, Petersen R, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Perrin R, Shaw L, Khachaturian Z, Carrillo M, Potter W, Barnes L, Bernard M, González H, Ho C, Hsiao J, Jackson J, Masliah E, Masterman D, Okonkwo O, Perrin R, Ryan L, Silverberg N, Fleisher A, Lilly E, Weiner M, Sacrey D, Fockler J, Conti C, Veitch D, Neuhaus J, Jin C, Nosheny R, Ashford M, Flenniken D, Kormos A, Green R, Montine T, Conti C, Petersen R, Aisen P, Rafii M, Raman R, Jimenez G, Donohue M, Gessert D, Salazar J, Zimmerman C, Cabrera Y, Walter S, Miller G, Coker G, Clanton T, Hergesheimer L, Smith S, Adegoke O, Mahboubi P, Moore S, Pizzola J, Shaffer E, Sloan B, Beckett L, Harvey D, Donohue M, Jack C, Forghanian-Arani A, Borowski B, Ward C, Schwarz C, Jones D, Gunter J, Kantarci K, Senjem M, Vemuri P, Reid R, Fox N, Malone I, Thompson P, Thomopoulos S, Nir T, Jahanshad N, DeCarli C, Knaack A, Fletcher E, Harvey D, Tosun-Turgut D, Chen S, Choe M, Crawford K, Yushkevich P, Das S, Jagust W, Koeppe R, Reiman E, Chen K, Mathis C, Landau S, Morris J, Perrin R, Cairns N, Householder E, Franklin E, Bernhardt H, Taylor-Reinwald L, Shaw L, Trojanowki J, Korecka M, Figurski M, Toga A, Crawford K, Neu S, Saykin A, Nho K, Risacher S, Apostolova L, Shen L, Foroud T, Nudelman K, Faber K, Wilmes K, Weiner M, Thal L, Khachaturian Z, Hsiao J, Silbert L, Lind B, Crissey R, Kaye J, Carter R, Dolen S, Quinn J, Schneider L, Pawluczyk S, Becerra M, Teodoro L, Dagerman K, Spann B, Brewer J, Vanderswag H, Fleisher A, Ziolkowski J, Heidebrink J, Zbizek-Nulph L, Lord J, Zbizek-Nulph L, Petersen R, Mason S, Albers C, Knopman D, Johnson K, Villanueva-Meyer J, Pavlik V, Pacini N, Lamb A, Kass J, Doody R, Shibley V, Chowdhury M, Rountree S, Dang M, Stern Y, Honig L, Mintz A, Ances B, Morris J, Winkfield D, Carroll M, Stobbs-Cucchi G, Oliver A, Creech M, Mintun M, Schneider S, Geldmacher D, Love M, Griffith R, Clark D, Brockington J, Marson D, Grossman H, Goldstein M, Greenberg J, Mitsis E, Shah R, Lamar M, Samuels P, Duara R, Greig-Custo M, Rodriguez R, Albert M, Onyike C, Farrington L, Rudow S, Brichko R, Kielb S, Smith A, Raj B, Fargher K, Sadowski M, Wisniewski T, Shulman M, Faustin A, Rao J, Castro K, Ulysse A, Chen S, Sheikh M, Singleton-Garvin J, Doraiswamy P, Petrella J, James O, Wong T, Borges-Neto S, Karlawish J, Wolk D, Vaishnavi S, Clark C, Arnold S, Smith C, Jicha G, Khouli R, Raslau F, Lopez O, Oakley M, Simpson D, Porsteinsson A, Martin K, Kowalski N, Keltz M, Goldstein B, Makino K, Ismail M, Brand C, Thai G, Pierce A, Yanez B, Sosa E, Witbracht M, Kelley B, Nguyen T, Womack K, Mathews D, Quiceno M, Levey A, Lah J, Hajjar I, Cellar J, Burns J, Swerdlow R, Brooks W, Silverman D, Kremen S, Apostolova L, Tingus K, Lu P, Bartzokis G, Woo E, Teng E, Graff-Radford N, Parfitt F, Poki-Walker K, Farlow M, Hake A, Matthews B, Brosch J, Herring S, van Dyck C, Mecca A, MacAvoy M, Carson R, Varma P, Chertkow H, Vaitekunis S, Hosein C, Black S, Stefanovic B, Heyn C, Hsiung G, Kim E, Mudge B, Sossi V, Feldman H, Assaly M, Finger E, Pasternak S, Rachinsky I, Kertesz A, Drost D, Rogers J, Grant I, Muse B, Rogalski E, Robson J, Mesulam M, Kerwin D, Wu C, Johnson N, Lipowski K, Weintraub S, Bonakdarpour B, Pomara N, Hernando R, Sarrael A, Rosen H, Miller B, Perry D, Turner R, Johnson K, Reynolds B, MCCann K, Poe J, Sperling R, Johnson K, Marshall G, Yesavage J, Taylor J, Chao S, Coleman J, White J, Lane B, Rosen A, Tinklenberg J, Belden C, Spann B, Clark K, Zamrini E, Sabbagh M, Killiany R, Stern R, Mez J, Kowall N, Budson A, Obisesan T, Ntekim O, Wolday S, Khan J, Nwulia E, Nadarajah S, Lerner A, Ogrocki P, Tatsuoka C, Fatica P, Fletcher E, Maillard P, Olichney J, DeCarli C, Carmichael O, Bates V, Capote H, Rainka M, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Perrin A, Burke A, Scharre D, Kataki M, Tarawneh R, Kelley B, Hart D, Zimmerman E, Celmins D, Miller D, Ponto L, Smith K, Koleva H, Shim H, Nam K, Schultz S, Williamson J, Craft S, Cleveland J, Yang M, Sink K, Ott B, Drake J, Tremont G, Daiello L, Drake J, Sabbagh M, Ritter A, Bernick C, Munic D, Mintz A, O’Connelll A, Mintzer J, Wiliams A, Masdeu J, Shi J, Garcia A, Sabbagh M, Newhouse P, Potkin S, Salloway S, Malloy P, Correia S, Kittur S, Pearlson G, Blank K, Anderson K, Flashman L, Seltzer M, Hynes M, Santulli R, Relkin N, Chiang G, Lee A, Lin M, Ravdin L, Weiner M, Aisen P, Petersen R, Weiner M, Aisen P, Petersen R, Green R, Harvey D, Jack C, Jagust W, Morris J, Saykin A, Shaw L, Toga A, Trojanowki J, Neylan T, Grafman J, Green R, Montine T, Aisen P, Jimenez G, Donohue M, Gessert D, Salazar J, Zimmerman C, Walter S, Adegoke O, Mahboubi P, Danowski S, Coker G, Clanton T, Pizzola J, Shaffer E, Nguyen-Barrera C, Neylan T, Hayes J, Finley S, Harvey D, Donohue M, Jack C, Bernstein M, Borowski B, Gunter J, Senjem M, Kantarci K, Ward C, Tosun-Turgut D, Chen S, Landau S, Koeppe R, Foster N, Reiman E, Chen K, Morris J, Perrin R, Franklin E, Shaw L, Trojanowki J, Korecka M, Figurski M, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Potkin S, Shen L, Faber K, Kim S, Nho K, Wilmes K, Schneider L, Pawluczyk S, Becerra M, Teodoro L, Dagerman K, Spann B, Brewer J, Vanderswag H, Fleisher A, Stern Y, Honig L, Mintz A, Shah R, Sood A, Blanchard K, Fleischman D, Arfanakis K, Duara R, Varon D, Greig M, Doraiswamy P, Petrella J, James O, Borges-Neto S, Wong T, Porsteinsson A, Martin K, Thai G, Pierce A, Reist C, Yanez B, Sosa E, Witbracht M, Sadowsky C, Martinez W, Villena T, Rosen H, Perry D, Turner R, Johnson K, Reynolds B, MCCann K, Poe J, Sperling R, Johnson K, Marshall G, Belden C, Spann B, Clark K, Zamrini E, Sabbagh M, Obisesan T, Ntekim O, Nwulia E, Nadarajah S, Asthana S, Carlsson C, Peskind E, Petrie E, Li G, Yesavage J, Taylor J, Chao S, Coleman J, White J, Lane B, Rosen A, Tinklenberg J, Lin M, Chiang G, Ravdin L, Relkin N, O’Connelll A, Mintzer J, Wiliams A, Mackin S, Aisen P, Raman R, Jimenez-Maggiora G, Donohue M, Gessert D, Salazar J, Zimmerman C, Walter S, Adegoke O, Mahboubi P, Mackin S, Weiner M, Aisen P, Raman R, Jack C, Landau S, Saykin A, Toga A, DeCarli C, Koeppe R, Green R, Drake E, Weiner M, Aisen P, Raman R, Donohue M, Mackin S, Nelson C, Bickford D, Butters M, Zmuda M, Jack C, Bernstein M, Borowski B, Gunter J, Senjem M, Kantarci K, Ward C, Reyes D, Koeppe R, Landau S, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Faber K, Nho K, Nudelman K, Mackin S, Rosen H, Nelson C, Bickford D, Au Y, Scherer K, Catalinotto D, Stark S, Ong E, Fernandez D, Butters M, Zmuda M, Lopez O, Oakley M, Simpson D. Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2214634120. PMID: 36595679, PMCID: PMC9926270, DOI: 10.1073/pnas.2214634120.Peer-Reviewed Original ResearchConceptsChronological ageDomain-specific cognitive impairmentConvolutional neural networkCognitive impairmentBrain age estimatesExecutive functionNeurocognitive measuresNeurocognitive trajectoriesMild cognitive impairmentBrain ageNormal participantsCognitive declineCN individualsSymptom severityMagnetic resonance imagesCN participantsNeuroanatomic changesDeep learning modelsIndependent samplesBrain agingIndividual patternsParticipantsLearning modelImpairmentIndividuals
2022
Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging
Cabral‐Miranda F, Tamburini G, Martinez G, Ardiles A, Medinas D, Gerakis Y, Hung M, Vidal R, Fuentealba M, Miedema T, Duran‐Aniotz C, Diaz J, Ibaceta‐Gonzalez C, Sabusap C, Bermedo‐Garcia F, Mujica P, Adamson S, Vitangcol K, Huerta H, Zhang X, Nakamura T, Sardi S, Lipton S, Kennedy B, Henriquez J, Cárdenas J, Plate L, Palacios A, Hetz C. Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging. The EMBO Journal 2022, 41: embj2022111952. PMID: 36314651, PMCID: PMC9670206, DOI: 10.15252/embj.2022111952.Peer-Reviewed Original ResearchConceptsUnfolded protein responseER stress sensor IRE1Stress sensor IRE1IRE1/XBP1 signalingTranscription factor XBP1Mammalian brain agingNeurodegenerative diseasesProteostasis networkEndoplasmic reticulum stressProteomic profilingProtein responseCell senescenceGenetic disruptionBrain agingXBP1 expressionReticulum stressMammalian brainMajor risk factorActive formHealthy brain agingSynaptic functionXBP1Age-related cognitive declinePathwayHippocampal tissueAging the brain: multi-region methylation principal component based clock in the context of Alzheimer’s disease
Thrush KL, Bennett DA, Gaiteri C, Horvath S, Dyck CHV, Higgins-Chen AT, Levine ME. Aging the brain: multi-region methylation principal component based clock in the context of Alzheimer’s disease. Aging 2022, 14: 5641-5668. PMID: 35907208, PMCID: PMC9365556, DOI: 10.18632/aging.204196.Peer-Reviewed Original ResearchConceptsDisease risk increasesBrain agingAD brain tissueΕ4 carrier statusClinical AD dementiaMultiple brain regionsEpigenetic alterationsReligious Orders StudyAD dementiaTest-retest reliabilityCortical samplesAD riskEpigenetic age accelerationSubcortical regionsPathologic ADAlzheimer's diseaseBrain regionsBrain tissueEpigenetic clocksCarrier statusStrong associationRush MemoryAge accelerationRisk increaseAging ProjectCharacterizing 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
Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups
Clausen AN, Fercho KA, Monsour M, Disner S, Salminen L, Haswell CC, Rubright EC, Watts AA, Buckley MN, Maron-Katz A, Sierk A, Manthey A, Suarez-Jimenez B, Olatunji BO, Averill CL, Hofmann D, Veltman DJ, Olson EA, Li G, Forster GL, Walter H, Fitzgerald J, Théberge J, Simons JS, Bomyea JA, Frijling JL, Krystal JH, Baker JT, Phan KL, Ressler K, Han LKM, Nawijn L, Lebois LAM, Schmaal L, Densmore M, Shenton ME, van Zuiden M, Stein M, Fani N, Simons RM, Neufeld RWJ, Lanius R, van Rooij S, Koch SBJ, Bonomo S, Jovanovic T, deRoon-Cassini T, Ely TD, Magnotta VA, He X, Abdallah CG, Etkin A, Schmahl C, Larson C, Rosso IM, Blackford JU, Stevens JS, Daniels JK, Herzog J, Kaufman ML, Olff M, Davidson RJ, Sponheim SR, Mueller SC, Straube T, Zhu X, Neria Y, Baugh LA, Cole JH, Thompson PM, Morey RA. Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups. Brain And Behavior 2021, 12: e2413. PMID: 34907666, PMCID: PMC8785613, DOI: 10.1002/brb3.2413.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderEffects of PTSDBrain-PADBrain ageMale controlsOld maleStress disorderAge-related brain changesStructural magnetic resonance imagingBrain structural magnetic resonance imagingOlder age groupsMagnetic resonance imagingChronological ageSubset of controlsContext of PTSDControl subjectsBrain changesBrain agingFuture longitudinal researchTreatment approachesLinear mixed effects modelsAdult subjectsResonance imagingAge groupsPTSD assessmentLower cerebral oxygen utilization is associated with Alzheimer’s disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers
Robb W, Khan O, Ahmed H, Li J, Moore E, Cambronero F, Pechman K, Liu D, Gifford K, Landman B, Donahue M, Hohman T, Jefferson A. Lower cerebral oxygen utilization is associated with Alzheimer’s disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers. Cerebrovascular And Brain Metabolism Reviews 2021, 42: 642-655. PMID: 34743630, PMCID: PMC9051148, DOI: 10.1177/0271678x211056393.Peer-Reviewed Original ResearchConceptsEpisodic memory performanceCognitive performancePathogenesis of Alzheimer's diseaseMemory performanceAlzheimer's disease-related neurodegenerationPoorer cognitive performanceE4 carriersLateral ventricle volumeExecutive functionEpisodic memoryOxygen homeostasisDisease-related neurodegenerationAlzheimer's diseaseBrain agingCognitive impairmentNeuroimaging variablesE4 statusCerebral metabolic rateVentricle volumeOlder adultsBad languageHippocampalNeurodegenerationMetabolic rateMetabolism
2020
Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation
Kelmer Sacramento E, Kirkpatrick J, Mazzetto M, Baumgart M, Bartolome A, Di Sanzo S, Caterino C, Sanguanini M, Papaevgeniou N, Lefaki M, Childs D, Bagnoli S, Terzibasi Tozzini E, Di Fraia D, Romanov N, Sudmant P, Huber W, Chondrogianni N, Vendruscolo M, Cellerino A, Ori A. Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation. Molecular Systems Biology 2020, 16: msb209596. PMID: 32558274, PMCID: PMC7301280, DOI: 10.15252/msb.20209596.Peer-Reviewed Original ResearchConceptsProtein homeostasisProteasome activityPost-transcriptional mechanismsAge-regulating proteinDriver of neurodegenerationProteome dynamicsProtein complexesTranscriptomic dataProtein aggregatesAge-related neurodegenerationProteomic signatureAssembly/Loss of stoichiometryProteasome levelsEarly eventsProteinHomeostasisProgressive lossNeurodegenerationCausative eventAging processTranscriptomicsNothobranchiusBrain agingRibosomes
2019
Association of Accelerometer-Measured Light-Intensity Physical Activity With Brain Volume
Spartano NL, Davis-Plourde KL, Himali JJ, Andersson C, Pase MP, Maillard P, DeCarli C, Murabito JM, Beiser AS, Vasan RS, Seshadri S. Association of Accelerometer-Measured Light-Intensity Physical Activity With Brain Volume. JAMA Network Open 2019, 2: e192745. PMID: 31002329, PMCID: PMC6481600, DOI: 10.1001/jamanetworkopen.2019.2745.Peer-Reviewed Original ResearchConceptsLight-intensity physical activityTotal brain volumeHigher total brain volumeMagnetic resonance imagingPA guidelinesPhysical activityBrain volumeBrain agingVigorous PA levelsCommunity-based cohort studyPA levelsBrain magnetic resonance imagingAssociation of accelerometerCurrent PA guidelinesBrain MRI measuresFramingham Heart Study participantsVigorous physical activityAdditional hourMost older adultsFramingham Heart StudyHigher brain volumesCohort studyDementia preventionDementia riskMean age
2016
Apolipoprotein ɛ4 breaks the association between declarative long-term memory and memory-based orienting of spatial attention in middle-aged individuals
Salvato G, Patai E, McCloud T, Nobre A. Apolipoprotein ɛ4 breaks the association between declarative long-term memory and memory-based orienting of spatial attention in middle-aged individuals. Cortex 2016, 82: 206-216. PMID: 27395443, PMCID: PMC4981431, DOI: 10.1016/j.cortex.2016.06.002.Peer-Reviewed Original ResearchConceptsDeclarative long-term memoryOrienting of spatial attentionLong-term memoryApo E4 genotypeSpatial attentionModulates declarative memoryMiddle-aged individualsVisuo-spatial attentionIdentification of cognitive dysfunctionAlzheimer's diseaseE4 genotypeDeclarative memoryExplicit memoryMemory deficitsAttention taskE4 carriersGrowing body of studiesCognitive dysfunctionBrain agingLate-onset Alzheimer's diseaseBody of studiesMemory systemAPOE e4 carriersBrain occurringMemory
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