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Record W2912509763 · doi:10.1038/s41598-019-38793-3

Predicting Short-term MCI-to-AD Progression Using Imaging, CSF, Genetic Factors, Cognitive Resilience, and Demographics

2019· article· en· W2912509763 on OpenAlexafffund
Yogatheesan Varatharajah, Vijay K. Ramanan, Ravishankar K. Iyer, Prashanthi Vemuri, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, Andrew J. Saykin, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John C. Morris, Leslie M. Shaw, Zaven S. Khachaturian, Greg Sorensen, Marı́a C. Carrillo, Lew Kuller, Marc Raichle, Steven M. Paul, Peter J. Davies, Howard Fillit, Franz Hefti, David M. Holtzman, M. Marcel Mesulam, William C. Potter, Peter J. Snyder, Adam J. Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matt A. Bernstein, Nick C. Fox, Paul M. Thompson, Norbert Schuff, Bret Borowski, Jeff Gunter, Matthew L. Senjem, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Susan Landau, Nigel J. Cairns, Erin Franklin, Lisa Taylor‐Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana Foroud, Steven Potkin, Kelley Faber, Sungeun Kim, Kwangsik Nho, Leon J. Thal, Neil Buckholtz, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph F. Quinn, Lisa C. Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James B. Brewer, Helen Vanderswag, Judith L. Heidebrink, Joanne Lord, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva‐Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau M. Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David G. Clark, John Brockington, Erik D. Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo‐Morrell, Ranjan Duara, Maria T. Greig‐Custo, Warren Barker, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Anaztasia Ulysse, Mrunalini Gaikwad, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges‐Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Gregory A. Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, Mary Ann Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel Silverman, Po H. Lu, George Bartzokis, Neill R. Graff‐Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging‐Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, John Rogers, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Emily Rogalskı, Kristine Lipowski, Sandra Weıntraub, Borna Bonakdarpour, Diana Kerwin, Chuang‐Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Jerome A. Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil W. Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan J. Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Owen Carmichael, Smita Kittur, Michael Borrie, T.-Y. Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre N. Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, B E Kelly, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Leslie Gordineer, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David C. Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chaing, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher

Bibliographic record

VenueScientific Reports · 2019
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsSunnybrook Health Science CentreSt Joseph's Health CentreMcGill UniversityJewish General Hospital
FundersNational Institute on AgingGenentechNational Institute of Neurological Disorders and StrokeIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaNovartis Pharmaceuticals CorporationU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Science FoundationNational Institutes of HealthU.S. Department of Health and Human ServicesFoundation for the National Institutes of HealthAlzheimer's Disease Neuroimaging InitiativeNational Center for Advancing Translational SciencesMeso Scale DiagnosticsAlzheimer's Association
KeywordsNeuroimagingDementiaCognitionMedicineDemographicsDiseasePsychologyPsychological resilienceBioinformaticsInternal medicineNeuroscienceBiology

Abstract

fetched live from OpenAlex

In the Alzheimer's disease (AD) continuum, the prodromal state of mild cognitive impairment (MCI) precedes AD dementia and identifying MCI individuals at risk of progression is important for clinical management. Our goal was to develop generalizable multivariate models that integrate high-dimensional data (multimodal neuroimaging and cerebrospinal fluid biomarkers, genetic factors, and measures of cognitive resilience) for identification of MCI individuals who progress to AD within 3 years. Our main findings were i) we were able to build generalizable models with clinically relevant accuracy (~93%) for identifying MCI individuals who progress to AD within 3 years; ii) markers of AD pathophysiology (amyloid, tau, neuronal injury) accounted for large shares of the variance in predicting progression; iii) our methodology allowed us to discover that expression of CR1 (complement receptor 1), an AD susceptibility gene involved in immune pathways, uniquely added independent predictive value. This work highlights the value of optimized machine learning approaches for analyzing multimodal patient information for making predictive assessments.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.008
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.008
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.341
Teacher spread0.316 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations94
Published2019
Admission routes2
Has abstractyes

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