NeuroImage (Aug 2022)
Predicting brain age from functional connectivity in symptomatic and preclinical Alzheimer disease
- Peter R. Millar,
- Patrick H. Luckett,
- Brian A. Gordon,
- Tammie L.S. Benzinger,
- Suzanne E. Schindler,
- Anne M. Fagan,
- Carlos Cruchaga,
- Randall J. Bateman,
- Ricardo Allegri,
- Mathias Jucker,
- Jae-Hong Lee,
- Hiroshi Mori,
- Stephen P Salloway,
- Igor Yakushev,
- John C. Morris,
- Beau M. Ances,
- Sarah Adams, MS,
- Ricardo Allegri, PhD,
- Aki Araki,
- Nicolas Barthelemy, PhD,
- Randall Bateman, MD,
- Jacob Bechara, BS,
- Tammie Benzinger, MD, PhD,
- Sarah Berman, MD, PhD,
- Courtney Bodge, PhD,
- Susan Brandon, BS,
- William (Bill) Brooks, MBBS,MPH,
- Jared Brosch, MD, PhD,
- Jill Buck, BSN,
- Virginia Buckles, PhD,
- Kathleen Carter, PhD,
- Lisa Cash, BFA,
- Charlie Chen, BA,
- Jasmeer Chhatwal, MD,PhD,
- Patricio Chrem Mendez, MD,
- Jasmin Chua, BS,
- Helena Chui, MD,
- Laura Courtney, BS,
- Carlos Cruchaga, PhD,
- Gregory S Day, MD,
- Chrismary DeLaCruz, BA,
- Darcy Denner, PhD,
- Anna Diffenbacher, MS,
- Aylin Dincer, BS,
- Tamara Donahue, MS,
- Jane Douglas, MPh,
- Duc Duong, BS,
- Noelia Egido, BS,
- Bianca Esposito, BS,
- Anne Fagan, PhD,
- Marty Farlow, MD,
- Becca Feldman, BS,BA,
- Colleen Fitzpatrick, MS,
- Shaney Flores, BS,
- Nick Fox, MD,
- Erin Franklin, MS,
- Nelly Joseph-Mathurin, PhD,
- Hisako Fujii, PhD,
- Samantha Gardener, PhD,
- Bernardino Ghetti, MD,
- Alison Goate, PhD,
- Sarah Goldberg, MS,LPC,NCC,
- Jill Goldman, MS,MPhil,CGC,
- Alyssa Gonzalez, BS,
- Brian Gordon, PhD,
- Susanne Gräber-Sultan, PhD,
- Neill Graff-Radford, MD,
- Morgan Graham, BA,
- Julia Gray, MS,
- Emily Gremminger, BA,
- Miguel Grilo, MD,
- Alex Groves,
- Christian Haass, PhD,
- Lisa Häsler, MSc,
- Jason Hassenstab, PhD,
- Cortaiga Hellm, BA,
- Elizabeth Herries, BA,
- Laura Hoechst-Swisher, MS,
- Anna Hofmann, MD,
- Anna Hofmann,
- David Holtzman, MD,
- Russ Hornbeck, MSCS, MPM,
- Yakushev Igor, MD,
- Ryoko Ihara, MD,
- Takeshi Ikeuchi, MD,
- Snezana Ikonomovic, MD,
- Kenji Ishii, MD,
- Clifford Jack, MD,
- Gina Jerome, MS,
- Erik Johnson, MD, PHD,
- Mathias Jucker, PhD,
- Celeste Karch, PhD,
- Stephan Käser, PHD,
- Kensaku Kasuga, MD,
- Sarah Keefe, BS,
- William Klunk, MD, PHD,
- Robert Koeppe, PHD,
- Deb Koudelis, MHS,RN,
- Elke Kuder-Buletta, RN,
- Christoph Laske, PhD,
- Allan Levey, MD, PHD,
- Johannes Levin, MD,
- Yan Li, PHD,
- Oscar Lopez, MD, MD,
- Jacob Marsh, BA,
- Ralph Martins, PhD,
- Neal Scott Mason, PhD,
- Colin Masters, MD,
- Kwasi Mawuenyega, PhD,
- Austin McCullough, PhD Candidate,
- Eric McDade, DO,
- Arlene Mejia, MD,
- Estrella Morenas-Rodriguez, MD, PhD,
- John Morris, MD,
- James Mountz, MD,
- Cath Mummery, PhD,
- N eelesh Nadkarni, MD, PhD,
- Akemi Nagamatsu, RN,
- Katie Neimeyer, MS,
- Yoshiki Niimi, MD,
- James Noble, MD,
- Joanne Norton, MSN, RN, PMHCNS-BC,
- Brigitte Nuscher,
- Ulricke Obermüller,
- Antoinette O'Connor, MRCPI,
- Riddhi Patira, MD,
- Richard Perrin, MD, PhD,
- Lingyan Ping, PhD,
- Oliver Preische, MD,
- Alan Renton, PhD,
- John Ringman, MD,
- Stephen Salloway, MD,
- Peter Schofield, PhD,
- Michio Senda, MD, PhD,
- Nicholas T Seyfried, D.Phil,
- Kristine Shady, BA, BS,
- Hiroyuki Shimada, MD, PhD,
- Wendy Sigurdson, RN,
- Jennifer Smith, PhD,
- Lori Smith, PA-C,
- Beth Snitz, PhD,
- Hamid Sohrabi, PhD,
- Sochenda Stephens, BS, CCRP,
- Kevin Taddei, BS,
- Sarah Thompson, PA-C,
- Jonathan Vöglein, MD,
- Peter Wang, PhD,
- Qing Wang, PhD,
- Elise Weamer, MPH,
- Chengjie Xiong, PhD,
- Jinbin Xu, PhD,
- Xiong Xu, BS, MS
Affiliations
- Peter R. Millar
- Department of Neurology, Washington University, St. Louis, MO 63110, USA; Corresponding author.
- Patrick H. Luckett
- Department of Neurology, Washington University, St. Louis, MO 63110, USA
- Brian A. Gordon
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
- Tammie L.S. Benzinger
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
- Suzanne E. Schindler
- Department of Neurology, Washington University, St. Louis, MO 63110, USA
- Anne M. Fagan
- Department of Neurology, Washington University, St. Louis, MO 63110, USA
- Carlos Cruchaga
- Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA
- Randall J. Bateman
- Department of Neurology, Washington University, St. Louis, MO 63110, USA
- Ricardo Allegri
- Department of Cognitive Neurology, Institute for Neurological Research Fleni, Buenos Aires, Argentina
- Mathias Jucker
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Jae-Hong Lee
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
- Hiroshi Mori
- Department of Clinical Neuroscience, Osaka City University Medical School, Nagaoka Sutoku University, Abenoku, Osaka 545-8585, Japan
- Stephen P Salloway
- Department of Neurology, Brown University, Providence, RI, USA
- Igor Yakushev
- Department of Nuclear Medicine, Technical University of Munich, Munich, Germany
- John C. Morris
- Department of Neurology, Washington University, St. Louis, MO 63110, USA
- Beau M. Ances
- Department of Neurology, Washington University, St. Louis, MO 63110, USA; Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
- Sarah Adams, MS
- Ricardo Allegri, PhD
- Aki Araki
- Nicolas Barthelemy, PhD
- Randall Bateman, MD
- Jacob Bechara, BS
- Tammie Benzinger, MD, PhD
- Sarah Berman, MD, PhD
- Courtney Bodge, PhD
- Susan Brandon, BS
- William (Bill) Brooks, MBBS,MPH
- Jared Brosch, MD, PhD
- Jill Buck, BSN
- Virginia Buckles, PhD
- Kathleen Carter, PhD
- Lisa Cash, BFA
- Charlie Chen, BA
- Jasmeer Chhatwal, MD,PhD
- Patricio Chrem Mendez, MD
- Jasmin Chua, BS
- Helena Chui, MD
- Laura Courtney, BS
- Carlos Cruchaga, PhD
- Gregory S Day, MD
- Chrismary DeLaCruz, BA
- Darcy Denner, PhD
- Anna Diffenbacher, MS
- Aylin Dincer, BS
- Tamara Donahue, MS
- Jane Douglas, MPh
- Duc Duong, BS
- Noelia Egido, BS
- Bianca Esposito, BS
- Anne Fagan, PhD
- Marty Farlow, MD
- Becca Feldman, BS,BA
- Colleen Fitzpatrick, MS
- Shaney Flores, BS
- Nick Fox, MD
- Erin Franklin, MS
- Nelly Joseph-Mathurin, PhD
- Hisako Fujii, PhD
- Samantha Gardener, PhD
- Bernardino Ghetti, MD
- Alison Goate, PhD
- Sarah Goldberg, MS,LPC,NCC
- Jill Goldman, MS,MPhil,CGC
- Alyssa Gonzalez, BS
- Brian Gordon, PhD
- Susanne Gräber-Sultan, PhD
- Neill Graff-Radford, MD
- Morgan Graham, BA
- Julia Gray, MS
- Emily Gremminger, BA
- Miguel Grilo, MD
- Alex Groves
- Christian Haass, PhD
- Lisa Häsler, MSc
- Jason Hassenstab, PhD
- Cortaiga Hellm, BA
- Elizabeth Herries, BA
- Laura Hoechst-Swisher, MS
- Anna Hofmann, MD
- Anna Hofmann
- David Holtzman, MD
- Russ Hornbeck, MSCS, MPM
- Yakushev Igor, MD
- Ryoko Ihara, MD
- Takeshi Ikeuchi, MD
- Snezana Ikonomovic, MD
- Kenji Ishii, MD
- Clifford Jack, MD
- Gina Jerome, MS
- Erik Johnson, MD, PHD
- Mathias Jucker, PhD
- Celeste Karch, PhD
- Stephan Käser, PHD
- Kensaku Kasuga, MD
- Sarah Keefe, BS
- William Klunk, MD, PHD
- Robert Koeppe, PHD
- Deb Koudelis, MHS,RN
- Elke Kuder-Buletta, RN
- Christoph Laske, PhD
- Allan Levey, MD, PHD
- Johannes Levin, MD
- Yan Li, PHD
- Oscar Lopez, MD, MD
- Jacob Marsh, BA
- Ralph Martins, PhD
- Neal Scott Mason, PhD
- Colin Masters, MD
- Kwasi Mawuenyega, PhD
- Austin McCullough, PhD Candidate
- Eric McDade, DO
- Arlene Mejia, MD
- Estrella Morenas-Rodriguez, MD, PhD
- John Morris, MD
- James Mountz, MD
- Cath Mummery, PhD
- N eelesh Nadkarni, MD, PhD
- Akemi Nagamatsu, RN
- Katie Neimeyer, MS
- Yoshiki Niimi, MD
- James Noble, MD
- Joanne Norton, MSN, RN, PMHCNS-BC
- Brigitte Nuscher
- Ulricke Obermüller
- Antoinette O'Connor, MRCPI
- Riddhi Patira, MD
- Richard Perrin, MD, PhD
- Lingyan Ping, PhD
- Oliver Preische, MD
- Alan Renton, PhD
- John Ringman, MD
- Stephen Salloway, MD
- Peter Schofield, PhD
- Michio Senda, MD, PhD
- Nicholas T Seyfried, D.Phil
- Kristine Shady, BA, BS
- Hiroyuki Shimada, MD, PhD
- Wendy Sigurdson, RN
- Jennifer Smith, PhD
- Lori Smith, PA-C
- Beth Snitz, PhD
- Hamid Sohrabi, PhD
- Sochenda Stephens, BS, CCRP
- Kevin Taddei, BS
- Sarah Thompson, PA-C
- Jonathan Vöglein, MD
- Peter Wang, PhD
- Qing Wang, PhD
- Elise Weamer, MPH
- Chengjie Xiong, PhD
- Jinbin Xu, PhD
- Xiong Xu, BS, MS
- Journal volume & issue
-
Vol. 256
p. 119228
Abstract
“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18–89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.
