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February 19, 2019; 92 (8) Article

Physical activity, common brain pathologies, and cognition in community-dwelling older adults

Aron S. Buchman, Lei Yu, Robert S. Wilson, Andrew Lim, Robert J. Dawe, Chris Gaiteri, Sue E. Leurgans, Julie A. Schneider, David A. Bennett
First published January 16, 2019, DOI: https://doi.org/10.1212/WNL.0000000000006954
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Article Information

vol. 92 no. 8 e811-e822
DOI: 
https://doi.org/10.1212/WNL.0000000000006954
PubMed: 
30651386
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received April 16, 2018
  • Accepted in final form October 16, 2018
  • First Published January 16, 2019.

Article Versions

Copyright & Usage: 
© 2019 American Academy of Neurology

Author Disclosures

    1. Aron S. Buchman, MD,
    2. Lei Yu, PhD,
    3. Robert S. Wilson, PhD,
    4. Andrew Lim, MD,
    5. Robert J. Dawe, PhD,
    6. Chris Gaiteri, PhD,
    7. Sue E. Leurgans, PhD,
    8. Julie A. Schneider, MD, MS and
    9. David A. Bennett, MD
  1. Aron S. Buchman, MD,
    2. 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. (1) NIH R01AG17917, co-I, 2001-19; NIH R01AG022018 co-I, 2010-2020, (2) R01AG043379 (PI), 2012-2017, R01NS078009 (PI), 2012-2017, R01AG047976 (PI), 2015-2020 R56AG059732(PI), 2018-2019

    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. Lei Yu, PhD,
    3. Scientific Advisory Boards:

    1. Texas Alzheimer's Research and Care Consortium Scientific Review Panel

    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. NIA, R01AG053446, biostatistician, 2016-2021 NIA, RF1AG015819, biostatistician, 1998-2019 NIA, R01AG017917, biostatistician, 2001-2019 NIA, RF1AG036042, biostatistician, 2009-2021 NIA, U01AG046152, biostatistician, 2013-2018 NIA, R01AG054058, biostatistician, 2016-2021 NIA, R01AG034374, biostatistician, 2009-2020 NIA, R01AG033678, biostatistician, 2009-2020 NIH, R01DK099269, biostatistician, 2014-2018 NIA, R01AG052488, biostatistician, 2017-2022 NIA, R01AG050631, biostatistician, 2016-2021 NIA, RF1AG048056, biostatistician, 2014-2019

    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. Robert S. Wilson, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. (1) Aging, Neuropsychology, and Cognition, Consulting Editor, 2004-present; (2) Psychology and Aging, Consulting Editor, 2007-present; (3) Neuropsychology, Consulting Editor, 2014-present.

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Pain Therapeutics, Inc.

    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. (1) NIH/NIA R01AG17917, Co-I, 2001-2014; (2) NIH/NIA P30AG10161, Co-I, 1991-2014; (3) NIH/NIA R01AG34374, Co-I, 2008-2014; (4) NIH/NIA R01AG15819, Co-I, 1998-2014.

    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. Andrew Lim, MD,
    5. 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. In kind support of scientific equipment from ResMed Inc.

    Research Support, Government Entities:

    1. Grant # MSH136642 and MOP125934 (PI Lim) 06/01/2014 - 06/30/2019 Canadian Institutes of Health Research Identifying Genetic Determinants of Human Sleep and Circadian Rhythms Grant # MOP336806 (co-PIs Lim and Law) 07/01/2015 - 06/30/2018 Canadian Institutes of Health Research A framework for hybrid machine and human computation for the accurate and scalable analysis of human clinical EEG recordings Grant # R01NS78009 (PI, Buchman; Lim Sleep Consultant) 09/01/2012 - 08/30/2017 National Institutes of Health/NINDS Clinical Profile of PD Pathology Grant # R01AG051175 (PI, Lauderdale; Lim Toronto site PI) 09/01/2015 - 09/01/2018 National Institutes of Health/NIA Enhancing Sleep and Physical Activity Measurement in the HRS Family of Studies Grant #R01AG048108 (PI, Hu; Lim Sleep Consultant) 09/01/2015 - 09/01-2020 National Institutes of Health/NIA Neuropathology for Disrupted Multiscale Activity Control in Alzheimer's Disease Grant # R01AG052488 (PI Lim) 03/15/2017 ? 03/15/2022 National Institutes of Health/NIA The overall goal of this study is to quantify the contributions of, and identify brain mechanisms linking, sleep and circadian rhythm disruption to cognitive decline and incident AD in older adults Grant # ER-16-12-034 (PI Lim) 06/01/2017 ? 05/31/2019 Ontario Ministry of Innovation (Early Researcher Award) The Ontario Sleep and Brain Health Study - An Extension of the Ontario Sleep Health Study to Examine the Links Between Sleep and Brain Health in Working-Age Ontarians The research goal of this study is to reveal the impact of sleep/circadian disruption on cognition, dementia-related brain changes, and dementia risk. This will provide the foundation to use minimally-invasive sleep/circadian screening to identify adults at risk for dementia, and ultimately support sleep/circadian-targeted interventions to prevent it.

    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. Robert J. Dawe, PhD,
    6. 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. (1) NIA, R01AG053446, Biomedical Engineer, 2016-2018 (2) NIA, RF1AG015819, Biomedical Engineer, 2016-2018 (3) NIA, P30AG010161, Biomedical Engineer, 2016-2018 (4) NIA, R01AG034374, Biomedical Engineer, 2016-2018 (5) NIA, R01AG056352, Biomedical Engineer, 2017-2018 (6) NIA, R01AG052488, Biomedical Engineer, 2017-2018

    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

  6. Chris Gaiteri, PhD,
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH/NIA R01AG057911 2017-2018 (PI) NIH/NIA R01AG061798 2018 (PI)

    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

  7. Sue E. Leurgans, PhD,
    8. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. (1) Neurology, Associate Editor for Statistics, 2015-

    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. (1) NIH: P30 AG010161 (ADC), core Leader and statistician, 2007-present (2) NIH: R01 AG042210, statistician, 2011-present (3) NIH: R01 NS078009, statistician, 2012-present (4) NIH: P20 MD006886, statistician 2013-present (5) NIH: RF1 AG015819, statisician, 2015-present (6) NIH: U02 AG046152-S1, statisician, 2015-Aug, 2018 (7) NIH R01 AG034374, statistician, 2015-present (8) NIH: R01 AG047976, statistician, 2014-present (9) NIH: R01 AG033570, statistician, 2015-present (10) NIH: R01 AG051641, statistician, 2016-present (11) NIH: R01 AG054476, statistician, 2016-present (12) NIH: R01 AG054057, statistician, 2016-present (13) NIH: UH2NS100599, statistician, 2016-present (14) NIH: R01 AG054058, statistician, 2017-present

    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

  8. Julie A. Schneider, MD, MS and
    9. Scientific Advisory Boards:

    1. (1) Medical Scientific Advisory Board, Alzheimer's Association (2) Scientific Advisory Board, Fondation Plan Alzheimer, France (3) Scientific Advisory Board of the Dutch CAA Foundation (4) Scientific External Advisory Board, University of Washington/Group Health Alzheimer's Disease Patient Registry/Adult Changes in Thought study.? Principal Investigator: Dr. Eric Larson External Advisory Board (5) New York University ? Alzheimer?s Disease Core Center (2/2017 ? Invited Chair of External Advisory Committee)(6) AVID radiopharmaceuticals (7)Genetech (8) Grifols (9) Eli Lilly

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. 2005-current Journal Histochemistry and Cytochemistry (Monitoring editor) 2013-current Editorial Board, Journal of Neuropathology and Experimental Neurology. 2017 - Lancet Neurology

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) AVID radiopharmaceuticals (2) Genentech (3) Grifols (4) Eli Lilly (5) National Hockey League (6) National Football League (7) Neurovision

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. AVID radiopharmaceutical phase III clinical trial Neuropathologist 2010-2011 NeuroVision Imaging, LLC

    Research Support, Government Entities:

    1. UH2NS100599 (MPI: Schneider & Arfanakis) 9/1/16- 8/31/21 NIH Multimodal MRI biomarkers of small vessel disease for older persons with and without dementia. Overall goal is to use ex-vivo and in-vivo imaging in a community cohort of older persons with and without dementia to develop an imaging biomarker and test other promising biomarkers of age-related vascular pathologies. R01AG042210 (Schneider) 7/1/12-3/31/17 National Institute of Aging Epidemiologic study of TDP-43 pathology in aging and dementia The major goal of the grant is to test the hypothesis that TDP-43 pathology in the aging brain is a separate disease increases the odds of dementia with a distinct cognitive phenotype, and specific genetic risk factors, separate from AD and other pathologies. P30AG010161 (Bennett) 9/30/91-6/30/16 National Institute on Aging Rush Alzheimer?s Disease Core Center The major goals of this Core Center Grant are to provide core infrastructure support for research on aging/AD. R01AG017917 (Bennett) 9/30/01-3/31/19 National Institute on Aging Epidemiologic Study of Neural Reserve and Neurobiology of Aging The major goal of the continuation of MAP is to discover additional proteins associated with the slope of cognitive decline, after accounting for the effects of common pathologies. RF1AG015819 (Bennett) 7/1/98-6/30/19 National Institute on Aging Risk Factors, Pathology, and Clinical Expressions of AD The overall goal of the proposal is to identify brain proteins and proteoforms linking AD risk genes to AD endophenotypes, i.e., AD pathology and cognitive decline. R01AG036042 (Bennett) 9/15/09-8/31/16 NIA, Roadmap, OBSSR Exploring the Role of the Brain Epigenome: Cognitive Decline and Life Experiences The major goal of the project is to explore the role of DNA methylation in modulating the effect of life experiences on cognition and dementia in older persons. U01AG046152 (Bennett & De Jager) 9/20/13?8/31/18 NIH/NIA Pathway discovery, validation and compound identification for Alzheimer's disease The overall goal of the proposed study is the discovery and preclinical validation of novel targets associated with molecular processes that lead to cognitive decline, the primary outcome of most AD trials. R01AG036836 (De Jager) 9/15/11-8/31/16 National Institute on Aging Exploring the Role of the Brain Transcriptome in Cognitive Decline The major goal is to investigate the transcriptome of human brain tissue to identify molecular pathways that contribute to cognitive decline. K01AG050823 (James) 8/15/15-4/30/20 NIA Cognitive decline after hospitalization in older adults: predictors and pathogenesis The overall goal of this research proposal is to identify prehospital risk factors and hospitalization characteristics that predict accelerated cognitive decline in older persons without dementia and to investigate whether subclinical dementia-related neuropathologies contribute to the development of cognitive decline after hospitalization. Role: Mentor

    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. (1) National football league (2) National Hockey League

  9. David A. Bennett, MD
    10. Scientific Advisory Boards:

    1. (1) Vigorous Minds, Scientific Advisory Board (2) Takeda Pharm - Adjudication committee AD4833/TOMM40_301 study (3) AbbVie - Data Monitoring Committee (4) EABs: India Institute of Science; MCSA; Columbia ADRC; CCNA; CIMA-Q, WFU, Emory, MODEL-AD, REGARDS (5) DMCs: HRS, MIDUS (6) National Advisory Council on Aging

    Gifts:

    1. $100,000 Potamkin Prize from the American Brain Foundation

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. (1) Neurology, Editorial Board; (2) Current Alzheimer Research, Editorial Board; (3) Neuroepidemiology, 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: P30AG10161, PI; RF1AG15819, PI; R01AG17917, PI; R01AG36042, PI; R01AG54058, PI; U01AG46152, MPI; U01AG46161, MPI; R01AG33678, co-I; R01AG34374, co-I;

    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

  1. From the Rush Alzheimer's Disease Center (A.S.B., L.Y., R.S.W., R.J.D., C.G., S.E.L., J.A.S., D.A.B.), and Departments of Neurological Sciences (A.S.B., L.Y., R.S.W., C.G., S.E.L., J.A.S., D.A.B.), Radiology (R.J.D.), Psychology (R.S.W.), and Pathology (Neuropathology) (J.A.S.), Rush University Medical Center, Chicago, IL; and Department of Neurology (A.L.), University of Toronto, Canada.
  1. Correspondence
    Dr. Buchman Aron_S_Buchman{at}rush.edu
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