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Predicting missing biomarker data in a longitudinal study of Alzheimer disease

  • Author(s): Lo, Raymond Y.
  • Jagust, William J.
  • Aisen, Paul
  • Jack, Clifford R.
  • Toga, Arthur W.
  • Beckett, Laurel
  • Gamst, Anthony
  • Soares, Holly
  • C. Green, Robert
  • Montine, Tom
  • Thomas, Ronald G.
  • Donohue, Michael
  • Walter, Sarah
  • Dale, Anders
  • Bernstein, Matthew
  • Felmlee, Joel
  • Fox, Nick
  • Thompson, Paul
  • Schuff, Norbert
  • Alexander, Gene
  • DeCarli, Charles
  • Bandy, Dan
  • Chen, Kewei
  • Morris, John
  • Lee, Virginia M.-Y.
  • Korecka, Magdalena
  • Crawford, Karen
  • Neu, Scott
  • Harvey, Danielle
  • Kornak, John
  • Saykin, Andrew J.
  • Foroud, Tatiana M.
  • Potkin, Steven
  • Shen, Li
  • Buckholtz, Neil
  • Kaye, Jeffrey
  • Dolen, Sara
  • Quinn, Joseph
  • Schneider, Lon
  • Pawluczyk, Sonia
  • Spann, Bryan M.
  • Brewer, James
  • Vanderswag, Helen
  • Heidebrink, Judith L.
  • Lord, Joanne L.
  • Petersen, Ronald
  • Johnson, Kris
  • Doody, Rachelle S.
  • Villanueva-Meyer, Javier
  • Chowdhury, Munir
  • Stern, Yaakov
  • Honig, Lawrence S.
  • Bell, Karen L.
  • Morris, John C.
  • Mintun, Mark A.
  • Schneider, Stacy
  • Marson, Daniel
  • Griffith, Randall
  • Clark, David
  • Grossman, Hillel
  • Tang, Cheuk
  • Marzloff, George
  • Toledo-Morrell, Leylade
  • Shah, Raj C.
  • Duara, Ranjan
  • Varon, Daniel
  • Roberts, Peggy
  • Albert, Marilyn S.
  • Pedroso, Julia
  • Toroney, Jaimie
  • Rusinek, Henry
  • de Leon, Mony J
  • De Santi, Susan M
  • Doraiswamy, P. Murali
  • Petrella, Jeffrey R.
  • Aiello, Marilyn
  • Clark, Christopher M.
  • Pham, Cassie
  • Nunez, Jessica
  • Smith, Charles D.
  • Given, Curtis A.
  • Hardy, Peter
  • Lopez, Oscar L.
  • Oakley, MaryAnn
  • Simpson, Donna M.
  • Ismail, M. Saleem
  • Brand, Connie
  • Richard, Jennifer
  • Mulnard, Ruth A.
  • Thai, Gaby
  • Mc-Adams-Ortiz, Catherine
  • Diaz-Arrastia, Ramon
  • Martin-Cook, Kristen
  • DeVous, Michael
  • Levey, Allan I.
  • Lah, James J.
  • Cellar, Janet S.
  • Burns, Jeffrey M.
  • Anderson, Heather S.
  • Laubinger, Mary M.
  • Bartzokis, George
  • Silverman, Daniel H.S.
  • Lu, Po H.
  • Graff-Radford MBBCH, Neill R
  • Parfitt, Francine
  • Johnson, Heather
  • Farlow, Martin
  • Herring, Scott
  • Hake, Ann M.
  • van Dyck, Christopher H.
  • MacAvoy, Martha G.
  • Benincasa, Amanda L.
  • Chertkow, Howard
  • Bergman, Howard
  • Hosein, Chris
  • Black, Sandra
  • Graham, Simon
  • Caldwell, Curtis
  • Hsiung, Ging-Yuek Robin
  • Feldman, Howard
  • Assaly, Michele
  • Kertesz, Andrew
  • Rogers, John
  • Trost, Dick
  • Bernick, Charles
  • Munic, Donna
  • Wu, Chuang-Kuo
  • Johnson, Nancy
  • Mesulam, Marsel
  • Sadowsky, Carl
  • Martinez, Walter
  • Villena, Teresa
  • Turner, Scott
  • Johnson, Kathleen B.
  • Behan, Kelly E.
  • Sperling, Reisa A.
  • Rentz, Dorene M.
  • Johnson, Keith A.
  • Rosen, Allyson
  • Tinklenberg, Jared
  • Ashford, Wes
  • Sabbagh, Marwan
  • Connor, Donald
  • Jacobson, Sandra
  • Killiany, Ronald
  • Norbash, Alexander
  • Nair, Anil
  • Obisesan, Thomas O.
  • Jayam-Trouth, Annapurni
  • Wang, Paul
  • Lerner, Alan
  • Hudson, Leon
  • Ogrocki, Paula
  • DeCarli, Charles
  • Fletcher, Evan
  • Carmichael, Owen
  • Kittur, Smita
  • Mirje, Seema
  • Borrie, Michael
  • Lee, T-Y
  • Bartha, Dr Rob
  • Johnson, Sterling
  • Asthana, Sanjay
  • Carlsson, Cynthia M.
  • Potkin, Steven G.
  • Preda, Adrian
  • Nguyen, Dana
  • Tariot, Pierre
  • Fleisher, Adam
  • Reeder, Stephanie
  • Bates, Vernice
  • Capote, Horacio
  • Rainka, Michelle
  • Hendin, Barry A.
  • Scharre, Douglas W.
  • Kataki, Maria
  • Zimmerman, Earl A.
  • Celmins, Dzintra
  • Brown, Alice D.
  • Gandy, Sam
  • Marenberg, Marjorie E.
  • Rovner, Barry W.
  • Pearlson, Godfrey
  • Anderson, Karen
  • Saykin, Andrew J.
  • Santulli, Robert B.
  • Englert, Jessica
  • Williamson, Jeff D.
  • Sink, Kaycee M.
  • Watkins, Franklin
  • Ott, Brian R.
  • Wu, Chuang-Kuo
  • Cohen, Ronald
  • Salloway, Stephen
  • Malloy, Paul
  • Correia, Stephen
  • Rosen, Howard J.
  • Miller, Bruce L.
  • Mintzer, Jacobo
  • et al.
Abstract

Objective:

To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD).

Methods:

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI.

Results:

CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD.

Conclusion:

The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.

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