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May 01, 2018; 90 (18) Article

Dissociable influences of APOE ε4 and polygenic risk of AD dementia on amyloid and cognition

Tian Ge, Mert R. Sabuncu, Jordan W. Smoller, Reisa A. Sperling, Elizabeth C. Mormino, For the Alzheimer's Disease Neuroimaging Initiative
First published March 28, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005415
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Article Information

vol. 90 no. 18 e1605-e1612
DOI: 
https://doi.org/10.1212/WNL.0000000000005415
PubMed: 
29592889
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received August 9, 2017
  • Accepted in final form February 9, 2018
  • First Published March 28, 2018.

Article Versions

Copyright & Usage: 
© 2018 American Academy of Neurology

Author Disclosures

    1. Tian Ge, PhD,
    2. Mert R. Sabuncu, PhD,
    3. Jordan W. Smoller, MD, ScD,
    4. Reisa A. Sperling, MD,
    5. Elizabeth C. Mormino, PhD;
    6. For the Alzheimer's Disease Neuroimaging Initiative
  1. Tian Ge, PhD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH, K99AG054573, Principal Investigator, 2017-2019

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Mert R. Sabuncu, PhD,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. I am on the editorial board of Medical Image Analysis Journal (Elsevier) I was co-editor of an edited volume entitled "Imaging Genetics", published by Elsevier

    Patents:

    1. NONE

    Publishing Royalties:

    1. I receive royalties for a book I published with Elsevier (entitled Machine Learning with Medical Imaging): https://www.elsevier.com/books/machine-learning-and-medical-imaging/wu/978-0-12-804076-8

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. 1) I am serving as a scientific consultant for a commercial start-up company in stealth mode. The company operates in a commercial domain unrelated to the study.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. ? National Institutes of Health (NIH) R01 Grant from NLM (1R01 LM012719) ?Novel Bioinformatics Strategies to Study Associations Between Genetic Variants and Neuroanatomical Shape? (PI: Sabuncu) Total funds: US$ 1,618,729 ? National Institutes of Health (NIH) R01 Grant from NIA (1R01 AG053949-01A1) ?Advanced machine learning algorithms that integrate genomewide, longitudinal MRI and demographic data to predict future cognitive decline toward dementia? (PI: Sabuncu) Total funds: US$ 2,137,500 ? National Science Foundation (NSF) ?Cornell Neurotechnology Hub for large scale, noninvasive recording of neural activity? (PI: Xu, Co-I: Sabuncu) Total funds: approx. US$ 9,000,000 ? National Institutes of Health (NIH) R21 Grant from NIA (1R21AG050122-01A1) ?Multi-modal Prediction of Future Clinical Dementia? (PI: Sabuncu) Total funds: US$ 478,500 ? National Institutes of Health (NIH) STTR Grant from NIA (1R41AG052246-01) ?A Structural Brain MRI Dementia Forecast Tool? (PI: Schmansky, Co-PI: Sabuncu) Total funds: US$ 225,000

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Jordan W. Smoller, MD, ScD,
    4. Scientific Advisory Boards:

    1. Oversight committee for the Klarman Family Foundation

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. 1999- Present Column Editor (Molecular Genetics) Harvard Review of Psychiatry 2007- Present Associate Editor American Journal of Medical Genetics (Neuropsychiatric Genetics) 2008- 2014 Editorial Board Member Depression and Anxiety 2009- Present Editorial Board Member CNS Spectrums 2010- Present Review Editor Frontiers in Child and Neurodevelopmental Psychiatry

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH Grants: U01 MH09443201 05/10/12 - 03/31/16 Role: Co-Investigator R01 MH092380-01A1 09/10/12 - 07/31/16 Role: Co-Investigator R01 MH078829 03/01/12 ? 02/28/17 Role: Subcontract PI K24 MH094614 05/07/12 - 04/30/17 Role: Principal Investigator R01 MH101486 09/16/13 - 06/30/17 Role: Principal Investigator R01 MH101425 08/01/13 - 04/30/18 Role: Co-Investigator UL1 TR001102 09/26/13 - 04/30/18 Role: Co-Investigator R56 HD085284 09/01/15 - 08/31/16 Role: Principal Investigator R01 MH106547-01 04/01/15 ? 03/31/18 Role: Principal Investigator U01 HG008685 09/01/15 ? 05/31/19 Role: Multi-PI 1OT2OD024612 09/27/16 - 02/28/18 Role: Multi-PI R01 MH110872 09/01/17 - 06/30/21 Role: Multi-PI R01 MH109539 07/01/16 - 03/31/21 Role: Co-investigator RO1 LM012719 12/01/17 - 11/30/21 Role: Subcontract PI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Tommy Fuss Fund Demarest Lloyd Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Reisa A. Sperling, MD,
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Commercial -Genentech Commercial- Otsuka pharmaceuticals Commercial- Lundbeck Commercial- Insightec Commercial- Pfizer Not for profit- travel for NIH

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Personal: 1) Abbvie, commercial 2) Biogen, commercial 3) Genentech, commercial 4) Bracket, commercial 5)Roche, commercial 6) Sanofi, commercial 7) Lundbeck, commercial 8)Avid, commercial 9)Isis Pharmaceuticals, commercial 10)Otsuka Pharmaceuticals, commercial 11) Merck, commercial 12) Eli Lilly, commercial 13) Insightec, commercial Spouse: 1)Lundbeck, commercial 2) Piramal Healthcare, commercial, 3) Siemens, commercial 4) Novartis

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Janssen- investigator-initiated imaging study, 2012-2014. Eli Lilly- clinical trial support 2014-present

    Research Support, Government Entities:

    1. 1) National Institute on Aging R01AG027435, Principal investigator, 2006-2017; 2) National Institute on Aging P01AG036694, principal investigator, 2010-2015; 3) National Institute on Aging P50AG005134, 2009-2014, Project leader; 4) National Institute on Aging U19 AG10483, Project Leader A4 trial, 2012-2017.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. American Health Assistance Foundation, principal investigator, 2010-2014. Alzheimer's Association, co-principal investigator, 2012- 2014.

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Elizabeth C. Mormino, PhD;
    6. Scientific Advisory Boards:

    1. Eli Lilly Scientific Advisory Board

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Consultant for (1) Biogen, (2) Eli Lilly and (3) Janssen Pharmaceuticals

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. Funding Source: NIH/NIA Grant number: K01AG051718 Role: PI Years: 5/2016-current

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. For the Alzheimer's Disease Neuroimaging Initiative
  1. From the Psychiatric and Neurodevelopmental Genetics Unit (T.G., J.W.S.), Center for Genomic Medicine, Massachusetts General Hospital; Departments of Psychiatry (T.G., J.W.S.) and Neurology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (T.G., M.R.S.), Massachusetts General Hospital, Harvard Medical School, Charleston; School of Electrical and Computer Engineering and Nancy E. and Peter C. Meinig School of Biomedical Engineering (M.R.S.), Cornell University, Ithaca, NY; Center for Alzheimer Research and Treatment (R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Neurology and Neurological Sciences (E.C.M.), Stanford University School of Medicine, Palo Alto, CA.
  1. Correspondence
    Dr. Mormino bmormino{at}stanford.edu
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