August 20, 2013; 81 (8) Article
Impaired default network functional connectivity in autosomal dominant Alzheimer disease
Jasmeer P. Chhatwal, Aaron P. Schultz, Keith Johnson, Tammie L.S. Benzinger, Clifford Jack, Beau M. Ances, Caroline A. Sullivan, Stephen P. Salloway, John M. Ringman, Robert A. Koeppe, Daniel S. Marcus, Paul Thompson, Andrew J. Saykin, Stephen Correia, Peter R. Schofield, Christopher C. Rowe, Nick C. Fox, Adam M. Brickman, Richard Mayeux, Eric McDade, Randall Bateman, Anne M. Fagan, Allison M. Goate, Chengjie Xiong, Virginia D. Buckles, John C. Morris, Reisa A. Sperling
First published July 24, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182a1aafe
Jasmeer P. Chhatwal
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MD, PhDAaron P. Schultz
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDKeith Johnson
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDTammie L.S. Benzinger
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MD, PhDClifford Jack Jr
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDBeau M. Ances
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MD, PhDCaroline A. Sullivan
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
BAStephen P. Salloway
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDJohn M. Ringman
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDRobert A. Koeppe
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDDaniel S. Marcus
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDPaul Thompson
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDAndrew J. Saykin
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PsyDStephen Correia
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDPeter R. Schofield
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhD, DScChristopher C. Rowe
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDNick C. Fox
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDAdam M. Brickman
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDRichard Mayeux
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDEric McDade
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
DORandall Bateman
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDAnne M. Fagan
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDAllison M. Goate
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
DPhilChengjie Xiong
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDVirginia D. Buckles
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
PhDJohn C. Morris
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDReisa A. Sperling
From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Department of Radiology (C.J.), Mayo Clinic, Rochester, MN; Department of Neurology, Butler Hospital (S.P.S.), and Department of Psychiatry (S.C.), Brown University School of Medicine, Providence, RI; Department of Neurology (J.M.R., P.T.), Easton Center for Alzheimer's Disease Research, University of California, Los Angeles; Department of Radiology (R.A.K.), University of Michigan School of Medicine, Ann Arbor; Department of Radiology (S.J.S.), IU Center for Neuroimaging, Indiana University School of Medicine, Indianapolis; Neuroscience Research Australia (P.R.S.), Sydney; School of Medical Sciences (P.R.S.), University of New South Wales, Sydney; Departments of Nuclear Medicine and Centre for PET (C.C.R.), Austin Health, University of Melbourne, Australia; Department of Neurology (N.C.F.), University College London, UK; Department of Neurology (A.M.B., R.M.), Columbia University College of Physicians and Surgeons, New York; Department of Neurology (E.M.), University of Pittsburgh School of Medicine, PA; and Department of Neurology (C.A.S., R.A.S.), Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
MDImpaired default network functional connectivity in autosomal dominant Alzheimer disease
Jasmeer P. Chhatwal, Aaron P. Schultz, Keith Johnson, Tammie L.S. Benzinger, Clifford Jack, Beau M. Ances, Caroline A. Sullivan, Stephen P. Salloway, John M. Ringman, Robert A. Koeppe, Daniel S. Marcus, Paul Thompson, Andrew J. Saykin, Stephen Correia, Peter R. Schofield, Christopher C. Rowe, Nick C. Fox, Adam M. Brickman, Richard Mayeux, Eric McDade, Randall Bateman, Anne M. Fagan, Allison M. Goate, Chengjie Xiong, Virginia D. Buckles, John C. Morris, Reisa A. Sperling
Neurology Aug 2013, 81 (8) 736-744; DOI: 10.1212/WNL.0b013e3182a1aafe
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Abstract
Objective: To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network.
Methods: Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO).
Results: We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO.
Conclusion: Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease.
GLOSSARY
- Aβ=
- amyloid-β;
- AD=
- Alzheimer disease;
- ADAD=
- autosomal dominant Alzheimer disease;
- ANOVA=
- analysis of variance;
- APP=
- amyloid precursor protein;
- CDR=
- Clinical Dementia Rating;
- DGC=
- DIAN Genetics Core;
- DIAN=
- Dominantly Inherited Alzheimer Network;
- DMN=
- default mode network;
- eYO=
- estimated years from expected symptom onset;
- fcMRI=
- functional connectivity MRI;
- GLM=
- general linear model;
- ICA=
- independent component analysis;
- LOAD=
- late-onset Alzheimer disease;
- LPC=
- left lateral parietal cortex;
- MCI=
- mild cognitive impairment;
- MNI=
- Montreal Neurological Institute;
- mPFC=
- medial prefrontal cortex;
- NCRAD=
- National Cell Repository for Alzheimer's Disease;
- PPC=
- precuneus/posterior cingulate;
- PSEN1=
- presenilin-1;
- PSEN2=
- presenilin-2;
- RPC=
- right lateral parietal cortex
Footnotes
↵* These authors contributed equally to this manuscript.
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.
Supplemental data at www.neurology.org
- Received March 12, 2013.
- Accepted in final form May 13, 2013.
- © 2013 American Academy of Neurology
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