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March 08, 2022; 98 (10) Research Article

Intake of Flavonoids and Flavonoid-Rich Foods and Mortality Risk Among Individuals With Parkinson Disease

A Prospective Cohort Study

Xinyuan Zhang, Samantha A. Molsberry, Tian-Shin Yeh, Aedin Cassidy, Michael A. Schwarzschild, Alberto Ascherio, Xiang Gao
First published January 26, 2022, DOI: https://doi.org/10.1212/WNL.0000000000013275
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Article Information

vol. 98 no. 10 e1064-e1076
DOI: 
https://doi.org/10.1212/WNL.0000000000013275
PubMed: 
35082171
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received July 16, 2021
  • Accepted in final form December 21, 2021
  • First Published January 26, 2022.

Article Versions

Copyright & Usage: 
© 2022 American Academy of Neurology

Author Disclosures

    1. Xinyuan Zhang, BS,
    2. Samantha A. Molsberry, PhD,
    3. Tian-Shin Yeh, MD, PhD,
    4. Aedin Cassidy, PhD,
    5. Michael A. Schwarzschild, MD, PhD,
    6. Alberto Ascherio, MD, DrPH and
    7. Xiang Gao, MD, PhD
  1. Xinyuan Zhang, BS,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Nutrition Journal, managing editor, 2019-present (2 years).

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Samantha A. Molsberry, PhD,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Tian-Shin Yeh, MD, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Aedin Cassidy, PhD,
    5. Scientific Advisory Boards:

    1. serve on grant review board for the United States Highbush Blueberry Council (USHBC) (with oversight from UDSDA)

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. USHBC funding for biomarker analyses and statistical analyses

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Michael A. Schwarzschild, MD, PhD,
    6. Scientific Advisory Boards:

    1. (1) Michael J. Fox Foundation for Parkinson's Research SAB (New York, NY) [2017-2019] (2) Cure Parkinson's Trust foundation Linked Clinical Trials program SAB (London, UK) [∼2012- ] (3) Corticobasal Degeneration Solutions Foundation SAB (Stockholm, Sweden) (4) NINDS/Udall Center of the Brigham & Womens Hospital -- Internal Advisory Committee (Boston, MA) (5) Eli Lilly & Company (clinical trial DSMB service); 2018- (6) Prevail Therapeutics (clinical advisory board); 2018-2019 (7) Parkinson's Foundation (Genetics initiative advisory board); 2018- (8) X-linked Dystonia Parkinsonism Clinical Center; 2018- (9) Denali Therapeutics (clinical advisory board); 2019 (10) Chase Therapeutics (clinical development advisory board, via PSG); 2019- 2020 (11) Partner Therapeutics, Inc. (clinical advisory board, via PSG) (12) NIH/NIA-funded TOPAZ trial SC via Sutter Health (13) NIH/NINDS-funded SPARX3 trial SC (14) STEPWISE trial SC via Farmer Family Foundation award (15) Bial Pharmaceuticals (via the Parkinson Study Group) (16) Biogen (via the Parkinson Study Group); 2021 -

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. •Denali Therapeutics, seminar speaker (2019) All others are non-profit entities: •Krembil Conference (Toronto) lecture (2019) •World Parkinson Congress, travel/honorarium (2006,2010,2013,2016,2019) •Parkinson Study Group symposium/meeting •for Cure Parkinson's Trust program SAB mtg. (Windsor, UK; Grand Rapids, MI) •for Cure Parkinson's Trust program SAB mtg. (Grand Rapids, MI); (travel)

    Editorial Boards:

    1. Journal of Adenosine and Caffeine Research, Editorial advisory board (2018-) Parkinsonism and Related Disorders, Editorial advisory board (2018-)

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Massachusetts General Hospital (sole employer; non-profit)

    Consultancies:

    1. (1) Harvard University (Parkinson's disease case reviews and epidemiology research); ∼2002-present (2) New Beta-Innovations, Inc (Hong Kong); 2016 (3) Eli Lilly & Company (clinical trial DSMB service); 2018- (4) Prevail Therapeutics, Inc (New York City); 2018-2019 (5) nQ Medical (Cambridge, MA); 2019 (6) Denali Therapeutics (Nice, France); 2019 (7) Chase Therapeutics (Washington, DC); 2019 (8) Biogen (virtual); 2021-December+

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. •NIH R01 NS110879 (PI) 08/01/19 – 05/31/24 •NIH U01 NS107009 (a PI) 07/01/18 to 04/30/23 •NIH R01NS102735 (Co-Investigator [Xiqun Chen, PI]) 4/1/18 - 3/31/23 •NIH R13 NS111953 (PI) 04/01/19 – 03/31/22 •NIH U01 NS090259 (PI) 9/1/2015 to 6/30/2020 •NIH U13 NS103523 (PI) 07/01/17 - 06/30/18 •NIH R13 NS098746 (PI) 07/01/16 - 06/30/17 •DoD W81XWH-14-1-0131 (Collaborator [A. Ascherio, PI]) 05/15/14 - 05/14/15 •NIH R21 NS090246 (Co-Investigator [Xiqun Chen, PI]) 04/01/15 - 03/31/17 •NIH R01 (Collaborator [A. Ascherio, PI]) •NIH R13 NS090879 (PI) 09/22/14 - 08/31/15 •R21 NS084710 (dual PI: Schwarzschild) 7/1/13-6/30/15 NIH/NINDS “Role of urate in protecting mitochondrial function in the brain” •K24 NS060991 (PI: Schwarzschild) 7/1/08-6/30/13 NIH/NINDS

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. grant support via my institution (MGH) on projects for which I am the Principal Investigator: (1) Michael J. Fox Foundation/ASAP (2) Parkinson's Foundation (3) Farmer Family Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. license fee distributions: (1) Adenosine A2A receptor knockout mice, via MGH (which receives payments from The Jackson Laboratory via licensing agreements); ∼2001-present (2) floxed urate oxidase mice, via MGH; 2020-

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Alberto Ascherio, MD, DrPH and
    7. Scientific Advisory Boards:

    1. University of Rochester - Scientific Advisory Board of NIH-funded study

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. NorthShore University HealthSystem, Evanston IL, 2019. Honorarium for talk on neurodegenerative diseases. University of Oslo, Norway. Honorarium as PhD defense opponent.

    Editorial Boards:

    1. 1) Journal of Parkinson Disease, Editorial board

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH R01 NS073633; 2011-2017; Role: PI DoD W81XWH-14-1-0131; 2014-2019; Role: PI NIH R01 NS045893; 2013-2018; Role: PI NIH 1U01NS-90259; 2015-2020; Role: PI of subcontract NIH R01 NS089619-01A1; 2015-2020; Role: PI NIH R01 NS097723; 2016-2021; Role: Co-Investigator NIH R01 NS103891; 2018-2023; Role: PI CDMRP MS170116; 2018-2021; Role: PI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. ALS Association; 2019-2020; Role: PI

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Xiang Gao, MD, PhD
    8. Scientific Advisory Boards:

    1. Chair, Nutritional Epidemiology Research Interest Sections, American Society for Nutrition

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Serves on the editorial boards of Advances in Nutrition and Journals of Human Genetics.

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Dr Gao have received grants from the National Institute of Neurological Disorders and Stroke

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Department of Nutritional Sciences (X.Z., X.G.), Pennsylvania State University, University Park; Departments of Nutrition (S.A.M., T.-S.Y., A.A.) and Epidemiology (T.-S.Y., A.A.), Harvard T.H. Chan School of Public Health; Channing Division of Network Medicine (T.-S.Y., A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Institute for Global Food Security (A.C.), Queen's University Belfast, Northern Ireland; and Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston. Dr. Yeh is currently with Nuffield Department of Population Health, Big Data Institute, University of Oxford, UK.
  1. Correspondence
    Dr. Gao xxg14{at}psu.edu
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