Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT.


Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
05 05 2020
Historique:
received: 29 06 2019
accepted: 02 12 2019
pubmed: 18 4 2020
medline: 22 8 2020
entrez: 18 4 2020
Statut: ppublish

Résumé

To investigate whether vitamin D, smoking, and anti-Epstein-Barr virus (EBV) antibody concentrations predict long-term cognitive status and neuroaxonal injury in multiple sclerosis (MS). This study was conducted among 278 patients with clinically isolated syndrome who participated in the clinical trial BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) and completed the 11-year assessment (BENEFIT-11). We measured serum 25-hydroxyvitamin-D (25(OH)D), cotinine (smoking biomarker), and anti-Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) at baseline and at months 6, 12, and 24 and examined whether these biomarkers contributed to predict Paced Auditory Serial Addition Test (PASAT)-3 scores and serum neurofilament light chain (NfL) concentrations at 11 years. Linear and logistic regression models were adjusted for sex, baseline age, treatment allocation, steroid treatment, multifocal symptoms, T2 lesions, and body mass index. Higher vitamin D predicted better, whereas smoking predicted worse cognitive performance. A 50-nmol/L higher mean 25(OH)D in the first 2 years was related to 65% lower odds of poorer PASAT performance at year 11 (95% confidence intervals [95% CIs]: 0.14-0.89). Standardized PASAT scores were lower in smokers and heavy smokers than nonsmokers ( Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS.

Identifiants

pubmed: 32300060
pii: WNL.0000000000009371
doi: 10.1212/WNL.0000000000009371
pmc: PMC7274920
doi:

Substances chimiques

Adjuvants, Immunologic 0
Antibodies, Viral 0
Biomarkers 0
Neurofilament Proteins 0
neurofilament protein L 0
Vitamin D 1406-16-2
Interferon beta-1b 145155-23-3
25-hydroxyvitamin D A288AR3C9H
Cotinine K5161X06LL

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1950-e1960

Investigateurs

Siegrid Strasser-Fuchs (S)
Thomas Berger (T)
Karl Vass (K)
Klaus V Toyka (KV)
Christian Sindic (C)
Benedicte Dubois (B)
Dominique Dive (D)
Valerie Delvaux (V)
Jan Debruyne (J)
Luanne Metz (L)
George Rice (G)
Marcelo Kremenchutzky (M)
Pierre Duquette (P)
Yves Lapierre (Y)
Mark Freedman (M)
A. John Petkau (AJ)
Anthony Traboulse (A)
Paul O'Connor (P)
Petr Stourac (P)
Radomir Talab (R)
Martin Valis (M)
Olga Zapletalova (O)
Ivana Kovarova (I)
Eva Medova (E)
Jiri Fiedler (J)
Jette Frederiksen (J)
Bruno Broche (B)
Thibault Moreau (T)
Patrick Vermersc (P)
Jean Pelletier (J)
Gilles Edan (G)
Michel Clanet (M)
David Brassat (D)
Pierre Clavelou (P)
Christine Lebrun-Frenay (C)
Olivier Gout (O)
Mikko Kallela (M)
Tuu Pirttila (T)
Juhani Ruutiainen (J)
Juha-Pek Erälinna (JP)
Keijo Koivisto (K)
Mauri Reunanen (M)
Irma Keskinarkaus (I)
Irina Elovaara (I)
Arno Villringer (A)
Holger Altenkirch (H)
Lars Bauer (L)
Mario Ghazi (M)
Christoph Pohl (C)
Karl Wessel (K)
Hans-Peter Hartung (HP)
Wolfgang Steinke (W)
Bernd Kieseier (B)
Hans Kölmel (H)
Patrick Oschmann (P)
Martin Berghoff (M)
Ricarda Diem (R)
Bernd Kitze (B)
Alexander Dressel (A)
Frank Hoffmann (F)
Karl Baum (K)
Stefan Jung (S)
Hela-Felicit Petereit (HF)
Dirk Reske (D)
Michael Sailer (M)
Jürgen Köhler (J)
Björn Tackenberg (B)
Luisa Klotz (L)
Reinhard Hohlfeld (R)
Tania Kuempfel (T)
Karl-Heinz Henn (KH)
Andreas Steinbrecher (A)
Klemens Angstwurm (K)
Hayrettin Tumani (H)
Ralf Gold (R)
Peter Rieckmann (P)
Christoph Kleinschnitz (C)
Samuel Komoly (S)
Gyula Gacs (G)
Gabor Jakab (G)
Gyula Panczel (G)
Tunde Csepany (T)
Laszlo Csiba (L)
Laszlo Vecsei (L)
Ariel Miller (A)
Dimitrios Karussis (D)
Joab Chapman (J)
Angelo Ghezzi (A)
Giancarlo Comi (G)
Vittorio Martinelli (V)
Paolo Gallo (P)
Vittorio Cosi (V)
Roberto Bergamaschi (R)
Luca Durelli (L)
Paola Cavalla (P)
Kjell-Morten Myhr (KM)
Andrzej Szczudlik (A)
Krzysztof Selmaj (K)
Zbigniew Stelmasiak (Z)
Halina Barosik-Psujek (H)
Ryszard Podemski (R)
Zdzislaw Maciejek (Z)
Slawomir Wawrzyniak (S)
Luis Cunha (L)
Sasa Sega-Jazbec (S)
Xavier Montalbán (X)
Txomin Arbizu (T)
Albert Saiz Hinarejos (A)
Joseba Barcena (J)
Sergio Martínez Yélamos (S)
Rafael Arroyo (R)
Oscar Fernandez (O)
Guillermo Izquierdo Ayuso (G)
Bonaventura Casanova i Estruch (B)
Jan Lycke (J)
Ludwig Kappos (L)
Ana de Vera (A)
Stacey Wu (S)
Jens Kuhle (J)
Ernst W. Radue (EW)
Heinrich Mattle (H)
Karsten Beer (K)
Jürg Kesselring (J)
Frederik Barkhof (F)
Chris H. Polman (CH)
Bernard Uitdehaag (B)
Bert Anten (B)
Raymond Hupperts (R)
Leo Visser (L)
Richard Coleman (R)
Jeremy Chataway (J)
David H. Miller (DH)
Jonathan O'Riordan (J)
Stephen Howell (S)
Henry F. McFarland (HF)

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 American Academy of Neurology.

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Auteurs

Marianna Cortese (M)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. mcortese@hsph.harvard.edu.

Kassandra L Munger (KL)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Elena H Martínez-Lapiscina (EH)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Christian Barro (C)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Gilles Edan (G)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Mark S Freedman (MS)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Hans-Peter Hartung (HP)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Xavier Montalbán (X)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Frederick W Foley (FW)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Iris Katharina Penner (IK)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Bernhard Hemmer (B)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Edward J Fox (EJ)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Sven Schippling (S)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Eva-Maria Wicklein (EM)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Ludwig Kappos (L)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Jens Kuhle (J)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Alberto Ascherio (A)

From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

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