Predicting alzheimer’s disease progression using multi-modal deep learning approach
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Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials.
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- Authors
- Lee, G., Nho, K., Kang, B., Sohn, K.-A., Kim, D., Initiative, F. A. D. N., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Carrillo, M., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Sather, T., Jiminez, G., Balasubramanian, A. B., Mason, J., Sim, I., 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. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Tha, L., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Ances, B., Carroll, M., Creech, M. L., Franklin, E., Mintun, M. A., Schneider, S., Oliver, A., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Love, M. N., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Grossman, H., Mitsis, E., Shah, R. C., deToledo-Morrell, L., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Duara, R., Varon, D., Greig, M. T., Roberts, P., Stern, Y., Honig, L. S., Bell, K. L., Albert, M., Onyike, C., D’Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Pogorelec, D. M., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Womack, K., Mathews, D., Quiceno, M., Doraiswamy, P. M., Petrella, J. R., Borges-Neto, S., Wong, T. Z., Coleman, E., Levey, A. I., Lah, J. J., Cella, J. S., Burns, J. M., Swerdlow, R. H., Brooks, W. M., Arnold, S. E., Karlawish, J. H., Wolk, D., Clark, C. M., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H. S., Lu, P. H., Bartzokis, G., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Lopez, O. L., Oakley, M., Simpson, D. M., Farlow, M. R., Hake, A. M., Matthews, B. R., Brosch, J. R., Herring, S., Hunt, C., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G.-Y. R., Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Lipowski, K., Weintraub, M., Bonakdarpour, B., Kerwin, D., Wu, C.-K., Johnson, N., Sadowsky, C., Villena, T., Turner, R. S., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Obisesan, T. O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Carmichael, O., Kittur, S., Borrie, M., Lee, T.-Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Flashman, L. A., Seltzer, M., Hynes, M. L., Santulli, R. B., Sink, K. M., Gordineer, L., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Finger, E., Pasternak, S., Rachinsky, I., Rogers, J., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L. L. B., Shim, H., Smith, K. E., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B. A., & Fargher, K.
- Affiliations
- Geisinger Neuroscience Institute (US)
- Indiana University Indianapolis (US)
- Ajou University (KR)
- Pennsylvania State University (US)
- University of California, San Francisco (US)
- Mayo Clinic (US)
- University of Pennsylvania (US)
- University of Southern California (US)
- Brigham and Women's Hospital (US)
- Washington University in St. Louis (US)
- Prevent Alzheimer’s Disease 2020 (US)
- Siemens (Germany) (DE)
- Alzheimer's Association (US)
- University of Pittsburgh (US)
- Albert Einstein College of Medicine (US)
- Alzheimer's Drug Discovery Foundation (US)
- Northwestern University (US)
- Brown University (US)
- University of Washington (US)
- University of California San Diego (US)
- University of London (GB)
- University of California, Los Angeles (US)
- University of Utah (US)
- Banner Alzheimer’s Institute (US)
- University of California, Irvine (US)
- Indiana University Bloomington (US)
- National Institute on Aging (US)
- Oregon Health & Science University (US)
- University of Alabama at Birmingham (US)
- Johns Hopkins University (US)
- University of California, Berkeley (US)
- Icahn School of Medicine at Mount Sinai (US)
- Rush University Medical Center (US)
- Baylor College of Medicine (US)
- Columbia University Irving Medical Center (US)
- New York University (US)
- Duke Medical Center (US)
- Emory University (US)
- University of Kansas Medical Center (US)
- University of Kentucky (US)
- University of Rochester Medicine (US)
- Yale University (US)
- Jewish General Hospital (CA)
- Sunnybrook Health Science Centre (CA)
- University of British Columbia (CA)
- St. Joseph's Hospital (CA)
- Cleveland Clinic (US)
- Palm Beach Neurology (US)
- Georgetown University Medical Center (US)
- Stanford University (US)
- Boston University (US)
- Howard University (US)
- Case Western Reserve University (US)
- University of California, Davis (US)
- St Joseph's Health Care (CA)
- Dent Neurologic Institute (US)
- The Ohio State University (US)
- Albany Medical College (US)
- Hartford Hospital (US)
- Dartmouth–Hitchcock Medical Center (US)
- Wake Forest University Health Sciences (US)
- Medical University of South Carolina (US)
- Nathan Kline Institute for Psychiatric Research (US)
- University of Iowa (US)
- Cornell University (US)
- University of South Florida (US)
- Corresponding author
- Sohn, Kyung-Ah
- Kim, Dokyoon
- ORCID
- Lee, Garam
- Nho, Kwangsik
- Kang, Byungkon
- Sohn, Kyung-Ah
- Kim, Dokyoon
- Weiner, Michael W.
- Aisen, Paul
- Petersen, Ronald
- Jack, Clifford R.
- Jagust, William
- Toga, Arthur W.
- Beckett, Laurel
- Green, Robert C.
- Saykin, Andrew J.
- Morris, John
- Shaw, Leslie M.
- Paul, Steven
- Davies, Peter
- Fillit, Howard
- Hefti, Franz
- Mesulam, M. Marcel
- Snyder, Peter
- Thomas, Ronald G.
- Donohue, Michael
- Walter, Sarah
- Balasubramanian, Archana B.
- Harvey, Danielle
- Fox, Nick
- Thompson, Paul
- DeCArli, Charles
- Vemuri, Prashanthi
- Jones, David
- Kantarci, Kejal
- Koeppe, Robert A.
- Reiman, Eric M.
- Chen, Kewei
- Landau, Susan
- Cairns, Nigel J.
- Korecka, Magdalena
- Crawford, Karen
- Foroud, Tatiana M.
- Potkin, Steven
- Shen, Li
- Faber, Kelley
- Kim, Sungeun
- Frank, Richard
- Hsiao, John
- Kaye, Jeffrey
- Quinn, Joseph
- Silbert, Lisa
- Ances, Beau
- Carroll, Maria
- Franklin, Erin
- Oliver, Angela
- Schneider, Lon S.
- Marson, Daniel
- Clark, David
- Geldmacher, David
- Roberson, Erik
- Love, Marissa Natelson
- Heidebrink, Judith L.
- Lord, Joanne L.
- Knopman, David
- Johnson, Kris
- Shah, Raj C.
- Duara, Ranjan
- Stern, Yaakov
- Honig, Lawrence S.
- Bell, Karen L.
- Albert, Marilyn
- Onyike, Chiadi
- D’Agostino, Daniel
- Kielb, Stephanie
- Galvin, James E.
- Cerbone, Brittany
- Rusinek, Henry
- Glodzik, Lidia
- Womack, Kyle
- Quiceno, Mary
- Doraiswamy, P. Murali
- Petrella, Jeffrey R.
- Wong, Terence Z.
- Levey, Allan I.
- Lah, James J.
- Burns, Jeffrey M.
- Swerdlow, Russell H.
- Brooks, William M.
- Arnold, Steven E.
- Karlawish, Jason H.
- Wolk, David
- Clark, Christopher M.
- Apostolova, Liana
- Silverman, Daniel H. S.
- Lu, Po H.
- Smith, Charles D.
- Hardy, Peter
- Sinha, Partha
- Johnson, Heather
- Farlow, Martin R.
- Hake, Ann Marie
- Brosch, Jared R.
- Porsteinsson, Anton P.
- Ismail, M. Saleem
- Thai, Gaby
- Carson, Richard E.
- Chertkow, Howard
- Bergman, Howard
- Stefanovic, Bojana
- Hsiung, Ging-Yuek Robin
- Feldman, Howard
- Bernick, Charles
- Bonakdarpour, Borna
- Kerwin, Diana
- Johnson, Nancy
- Turner, Raymond Scott
- Sperling, Reisa A.
- Johnson, Keith A.
- Marshall, Gad
- Yesavage, Jerome
- Taylor, Joy L.
- Lane, Barton
- Rosen, Allyson
- Sabbagh, Marwan N.
- Belden, Christine M.
- Jacobson, Sandra A.
- Kowall, Neil
- Killiany, Ronald
- Budson, Andrew E.
- Norbash, Alexander
- Obisesan, Thomas O.
- Lerner, Alan
- Tatsuoka, Curtis
- Maillard, Pauline
- Olichney, John
- Carmichael, Owen
- Johnson, Sterling
- Asthana, Sanjay
- Carlsson, Cynthia M.
- Preda, Adrian
- Nguyen, Dana
- Tariot, Pierre
- Burke, Anna
- Scharre, Douglas W.
- Kataki, Maria
- Pearlson, Godfrey D.
- Flashman, Laura A.
- Hynes, Mary L.
- Santulli, Robert B.
- Sink, Kaycee M.
- Williamson, Jeff D.
- Garg, Pradeep
- Ott, Brian R.
- Tremont, Geoffrey
- Salloway, Stephen
- Correia, Stephen
- Miller, Bruce L.
- Perry, David
- Mintzer, Jacobo
- Bachman, David
- Pasternak, Stephen
- Pomara, Nunzio
- Schultz, Susan K.
- Ponto, Laura L. Boles
- Shim, Hyungsub
- Relkin, Norman
- Ravdin, Lisa
- Smith, Amanda
- Venue
- Scientific Reports
- Published
- 2019-02-13
- Volume
- 9
- Issue
- 1
- Pages
- 1952-1952
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6374429
- OpenAlex
- W2914209001
- Cited by
- 406
- References
- 41
- Citations by year
- 2026: 35 · 2025: 59 · 2024: 84 · 2023: 66 · 2022: 54 · 2021: 56 · 2020: 38 · 2019: 13 · 2018: 1
- FWCI
- 32.00
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-08-01)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Scholarship@Western (Western University) (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Scholarship@Western (Western University) (submittedVersion, cc-by)
- Scholarship@Western (Western University) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM R01 LM012535)
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (NIA R03 AG054936)
- National Research Foundation of Korea (NRF-2016R1D1A1B03933875)
- Pennsylvania Department of Health (SAP 4100070267)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
- Keywords
- Alzheimer's disease, mild cognitive impairment, MCI conversion prediction, disease progression, multimodal deep learning, recurrent neural networks, neuroimaging biomarkers, cerebrospinal fluid biomarkers, ADNI, clinical trial stratification
- MeSH terms
- Deep Learning, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition, Cross-Sectional Studies, Female, Forecasting, Humans, Male, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Area Under Curve, Neuroimaging, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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