Trial reportNeurology2020
Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT.
Open access · bronzeAbstract readClinical Trial, Phase IIIMulticenter Study
In one paragraph
Trial report in Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Smoking, obesity, and disability worsening in PPMS: an analysis of the INFORMS original trial dataset.Journal of neurology · 2022Trial
- Epidemiological relevant effect biomarkers for thyroid hormone system related adverse outcome pathways: a literature review.Frontiers in pharmacology · 2026Review
- Mechanisms of Epstein-Barr virus-associated autoimmunity: a comparative overview.Frontiers in immunology · 2026Review
- Neuroprotective Roles of Vitamin D: Bridging the Gap Between Mechanisms and Clinical Applications in Cognitive Decline.International journal of molecular sciences · 2025Review
- Emerging Insights into the Role of Macrophages in Multiple Sclerosis: Pathogenesis and Potential Therapeutic Strategies.Journal of inflammation research · 2025Review
- Motivators and barriers for smoking cessation in people with multiple sclerosis: a qualitative study to inform the design of a tailored intervention.BMC public health · 2024Article
- Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis.Journal of neurology · 2024Article
- Serum neurofilament light chain: a novel biomarker for cardiovascular diseases in individuals without hypertension.Scientific reports · 2024Article
- Impact of tobacco smoking on disease-specific outcomes in common neurological disorders: A scoping review.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2024Article
- Correlation analysis between smoke exposure and serum neurofilament light chain in adults: a cross-sectional study.BMC public health · 2024Article
- Review
- Smoking and multiple sclerosis risk in black people: A nested case-control study.Multiple sclerosis and related disorders · 2024Article
- Modifiable risk factors of COVID-19 in patients with multiple sclerosis: a single-centre case-control study.Journal of neurology · 2023Article
- The roles of serum vitamin D and tobacco smoke exposure in insomnia: a cross-sectional study of adults in the United States.Frontiers in nutrition · 2023Article
- Cigarette smoking is associated with Herpesviruses in persons with and without serious mental illness.PloS one · 2023Article
- Article
- Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis?Neural regeneration research · 2022Review
- Macronutrients, vitamins and minerals in the diet of multiple sclerosis patients.Postepy psychiatrii neurologii · 2022Review
- The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Cerebrospinal fluid biomarkers and cognitive functions at multiple sclerosis diagnosis.Journal of neurology · 2022Article
Corrections and comments
- Commented on by
Authors and funding
18 authors at 2 institutions in 2 countries.
Marianna CorteseFrom 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 MungerFrom 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-LapiscinaFrom 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 BarroFrom 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 EdanFrom 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 FreedmanFrom 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 HartungFrom 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 MontalbánFrom 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 FoleyFrom 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 PennerFrom 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 HemmerFrom 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.ORCID 0000-0001-5985-6784
Edward J FoxFrom 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 SchipplingFrom 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 WickleinFrom 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 KapposFrom 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 KuhleFrom 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 AscherioFrom 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.
BENEFIT Study Group
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESDüsseldorf University Hospital · DE
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo 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).
methodsThis 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.
resultsHigher 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 (
conclusionsLower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS.
Indexed as
CognitionAdjuvants, ImmunologicAntibodies, ViralBiomarkersCotinineDemyelinating DiseasesDouble-Blind MethodEpstein-Barr Virus InfectionsFemaleFollow-Up StudiesHumansInterferon beta-1bMaleMultiple Sclerosis, Relapsing-RemittingNeurofilament ProteinsRisk Factors25-hydroxyvitamin DAdjuvants, ImmunologicAntibodies, ViralBiomarkersCotinineInterferon beta-1bneurofilament protein LNeurofilament ProteinsVitamin D
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