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Abstract

Objective:

To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies.

Methods:

We computed polygenic risk scores (PGRS) using summary statistics from the International Genomics of Alzheimer's Project genome-wide association study of AD. Associations between PGRS and AD markers (cognitive decline, clinical progression, hippocampus volume, and β-amyloid) were assessed within older participants with dementia. Associations between PGRS and hippocampus volume were additionally examined within healthy younger participants (age 18–35 years).

Results:

Within participants without dementia, elevated PGRS was associated with worse memory (p = 0.002) and smaller hippocampus (p = 0.002) at baseline, as well as greater longitudinal cognitive decline (memory: p = 0.0005, executive function: p = 0.01) and clinical progression (p < 0.00001). High PGRS was associated with AD-like levels of β-amyloid burden as measured with florbetapir PET (p = 0.03) but did not reach statistical significance for CSF β-amyloid (p = 0.11). Within the younger group, higher PGRS was associated with smaller hippocampus volume (p = 0.05). This pattern was evident when examining a PGRS that included many loci below the genome-wide association study (GWAS)–level significance threshold (16,123 single nucleotide polymorphisms), but not when PGRS was restricted to GWAS-level significant loci (18 single nucleotide polymorphisms).

Conclusions:

Effects related to common genetic risk loci distributed throughout the genome are detectable among individuals without dementia. The influence of this genetic risk may begin in early life and make an individual more susceptible to cognitive impairment in late life. Future refinement of polygenic risk scores may help identify individuals at risk for AD dementia.

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Supplementary Material

File (coinvestigators.pdf)
File (data_supplement.pdf)

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Information & Authors

Information

Published In

Neurology®
Volume 87Number 5August 2, 2016
Pages: 481-488
PubMed: 27385740

Publication History

Received: December 24, 2015
Accepted: April 22, 2016
Published online: July 6, 2016
Published in print: August 2, 2016

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Disclosure

E. Mormino received funding from NIH grant F32AG044054 and P01 AG036694. R. Sperling has served as a paid consultant for Abbvie, Biogen, Bracket, Genentech, Lundbeck, Roche, and Sanofi. She has served as a coinvestigator for Avid, Eli Lilly, and Janssen Alzheimer Immunotherapy clinical trials. She has spoken at symposia sponsored by Eli Lilly, Biogen, and Janssen. R. Sperling receives research support from Janssen Pharmaceuticals and Eli Lilly and Co. These relationships are not related to the content in the manuscript. She also receives research support from the following grants: P01 AG036694, U01 AG032438, U01 AG024904, R01 AG037497, R01 AG034556, K24 AG035007, P50 AG005134, U19 AG010483, R01 AG027435, Fidelity Biosciences, Harvard NeuroDiscovery Center, and the Alzheimer's Association. A. Holmes received funding from K01MH099232. R. Buckner reports personal fees from Pfizer that are not related to the content in the manuscript. P. De Jager received funding from R01AG036836. J. Smoller received funding from K24MH094614. M. Sabuncu received funding from K25EB013649. Go to Neurology.org for full disclosures.

Study Funding

This work was funded by NIH grants F32AG044054 (E.C.M.), P01AG036694 (R.A.S.), K01MH099232 (A.J.H.), R01AG036836 (P.L.D.), K24MH094614 (J.W.S.), and K25EB013649 (M.R.S.). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California. The data from younger participants were collected as part of the Brain Genomics Superstruct Project (http://neuroinformatics.harvard.edu/gsp/).

Authors

Affiliations & Disclosures

Elizabeth C. Mormino, PhD
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
Disclosure
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.
Funding Source: NIH/NIA Grant number: F32AG044054 Role: PI Years: 2/2015-current Funding Source: NIH/NIA Grant number: P01AG036694 Role: Co-investigator Years: 2/2015-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
Reisa A. Sperling, MD
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1)Commercial-Genentech travel 2)Not for Profit-Foundation for NIH- travel 3)Commercial- Otsuka Pharmaceuticals 4)Commercial- Lundbeck
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 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
Avram J. Holmes, PhD
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
Disclosure
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.
NIMH, K01MH099232, PI: Holmes, 2013-2018
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Brain & Behavior Research 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
Randy L. Buckner, PhD
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
Disclosure
Scientific Advisory Boards:
1.
paid consultant for Pfizer Scientific advisory board. 6 years.
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.
Pfizer
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.
R01 MH101486 (Smoller & Buckner) 09/16/13-06/30/17 0.83 cal NIH/NIMH $397,358 Neural and Genetic Basis of Negative Valance Traits The goal of this project is to define and validate a brain-based index of anxiety- and depression-related symptoms in order to provide novel insights into the biology of anxiety and depressive disorders, which may lead to biomarkers that can improve the diagnosis and targeted treatment of these conditions. Role: Co-Principle Investigator P01 AG036694 (Sperling) 07/15/10-06/30/15 1.20 cal NIH/NIA $117,1855 Impact of Amyloid on the Aging Brain The overall goals of the Program Project application are to elucidate the biological and clinical significance of amyloid deposition in clinically normal older individuals and to determine age-related functional and cognitive change in the absence of amyloid. Role: Principle Investigator of Project 1 R01 HD067744 (Valera) ??????????????????????????? 09/01/11-06/30/16 ?????????????? 0.12 cal NIH/NICHD ??????????????????????????????????????????????????????????? $280,421 The Role of Corticocerebellar Pathophysiology in Adult ADHD The long term objective of this proposal is to increase our understanding of the pathophysiology of attention deficit/hyperactivity disorder (ADHD) by furthering our knowledge regarding how the cerebellum and corticocerebellar circuits contribute to perceptual and motor timing abnormalities in ADHD. Role: Co-Investigator R01 AG046396 (Johnson) 01/01/14-12/31/18 0.12 cal NIH/NIA $499,107 Disentangling the contribution of tau to aging and AD The overall goal of this research is to determine the relationship of PET measures of PHF tau to Aβ deposition, brain structure and function, and cognition along the trajectories of aging and AD. Role: Co-Investigator P50 MH106435 (Haber) 04/1/15-03/31/20 3.00 cal NIH/NIMH $186,447 (Proj 3) / $84,193 (Core C) Neurcircuitry of OCD: Effects of Neuromodulation The overall goals of this Conte Center are to explore the circuitry of OCD in humans and develop methods for productively modulating that circuitry to alleviate symptoms. Project 3 seeks to develop methods to image networks at the level of individual subjects. Core C supports data management of neuroimaging across the Center. Role: Principle Investigator of Project 3 and Core C
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
Philip L. De Jager, MD, PhD
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
Disclosure
Scientific Advisory Boards:
1.
1. TEVA Neuroscience, member of advisory board 2. Genzyme/Sanofi, member of advisory board
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Biogen IDEC: speaker honoraria Source Healthcare Analytics Pfizer Inc: speaker honoraria TEVA: speaker honoraria
Editorial Boards:
1.
Journal of Neuroimmunology - member of the Editorial Board Neuroepigenetics - associate editor Multiple Sclerosis journal - member of the Editorial Board
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.
Biogen IDEC: research grant GSK: research grant Vertex: research grant Genzyme/Sanofi: research grant
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
National MS Society PI, 2008: JF2138A1
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
Jordan W. Smoller, MD, ScD
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
Disclosure
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 Grants: R01 MH085542 09/30/08 - 11/30/14 Role: Principal Investigator R01 MH081130 05/19/08 - 05/31/14 Role: Subcontract Investigator U01 MH087981 07/01/11 - 06/30/15 Role: Subcontract PI 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
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Tommy Fuss Fund Dearest 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
Mert R. Sabuncu, PhD
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
Disclosure
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, K25-EB013649, 2011-2016, PI NIH, R41-AG052246, 2015-2016, Co-PI
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
BrightFocus Foundation - Alzheimer's disease pilot grant (A2012333)
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
For the Alzheimer's Disease Neuroimaging Initiative
From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.

Notes

Correspondence to Dr. Mormino: [email protected]
Coinvestigators are listed at Neurology.org.
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

E.C.M.: conception and design of the study, analysis of data, statistical analysis, drafting the manuscript. R.A.S.: conception and design of the study. A.J.H.: conception and design of the study, analysis of data. R.L.B.: conception and design of the study. P.L.D.: conception and design of the study. J.W.S.: conception and design of the study. M.R.S.: conception and design of the study, analysis of data, statistical analysis, drafting the manuscript.

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