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February 19, 2013; 80 (8) Article

Microvascular brain pathology and late-life motor impairment

Aron S. Buchman, Lei Yu, Patricia A. Boyle, Steven R. Levine, Sukriti Nag, Julie A. Schneider, David A. Bennett
First published January 30, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182825116
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Article Information

vol. 80 no. 8 712-718
DOI: 
https://doi.org/10.1212/WNL.0b013e3182825116
PubMed: 
23365057
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received June 24, 2012
  • Accepted September 28, 2012
  • First Published January 30, 2013.

Article Versions

Copyright & Usage: 
© 2013 American Academy of Neurology

Author Disclosures

    1. Aron S. Buchman, MD,
    2. Lei Yu, PhD,
    3. Patricia A. Boyle, PhD,
    4. Steven R. Levine, MD,
    5. Sukriti Nag, MD, PhD,
    6. Julie A. Schneider, MD and
    7. 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, 2001-13; (2) NIH R01AG24480, PI, 2005-12, R01AG043379 (PI), 2012-2017, R01NS078009 (PI), 2012-2017

    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. 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 R01AG033678 [co-investigator], NIH R01AG024871 [co-investigator], NIH R01AG024871 [co-investigator], NIH P30AG010161 [co-investigator], NIH R01AG015819 [co-investigator], NIH R01HL096944 [co-investigator], NIH R01AG036042 [co-investigator], NIH R01AG038651 [co-investigator], NIH R01AG040039 [co-investigator], NIH R01AG034374 [co-investigator], NIH U01AG032984 [co-investigator]

    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. Patricia A. Boyle, 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. NIH/NIA R01AG034374, PI, 2009-2014NIH/NIA R01AF034119, Co-I, NIH/NIA R01AG033678, PI, 2009-2014

    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. Steven R. Levine, MD,
    5. Scientific Advisory Boards:

    1. (1) Independent Medical/Safety Monitor for NINDS-funded IMS 3, FAST MAG, INSTINCT, and CLEAR-ER(2) Adjudication committee for NINDS-funded WARCEF

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1) Genentech-sponsored investigator meeting - travel expenses reimbursement in 2010, 2011

    Editorial Boards:

    1. (1) MEDLINK, Associate Editor, 1996-present(2) National Stroke Association, scientific content advisor, 2010, 2011

    Patents:

    1. NONE

    Publishing Royalties:

    1. (1) Book: Transient Ischemic Attacks, Blackwell Futura, 2004

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Genentech-sponsored investigator meeting - consultant, 2010(2) Genentech study on cost-effectiveness of primary stroke centers, 2011 - consultant within a study group

    Speakers' Bureaus:

    1. (1)Medical Education Speakers Network, lecturer, 2008-2012(2)NCME, lecturer, 2008-2011

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1)NIH-NHLBI 1R01 HL096944, principal investigator, 2009-2013(2) NIH-NINDS 1UO1 NS044364, Independent safety monitor, 2003 - 2012(3) NIH-NINDS 1 U10 NS077378,PI, 2011 - 2017(4) NIH-NINDS 1 U10 NS080377, PI, 2012 - 2017(5) NIH-NINDS 1 R25 NS079211, MPI, 2012- 2017(6) The Patient-Centered Outcomes Research Institute (PCORI) 1IP2PI000781, scientific PI, 2012-2014(7) NIH-NIA 1 R01 AG040039, Co-I, 2011-2016(8) NIH-NINDS 2 P50 NS044283, safety monitor, 2008-2013(9) NIH-NINDS 2 U01 NS052220, independent medical monitor, 2005-2013

    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. Sukriti Nag, MD, 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. The blood-brain & Other neural barriers, Springer Science+ Business Media,Humana Press, 2011Nag S (Editor)

    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

  6. Julie A. Schneider, MD and
    7. Scientific Advisory Boards:

    1. 1. served on scientific advisory board for GE Healthcare(2010)2. served on scientific advisory board for Eli Lilly andCompany (2011)

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. 2005-current Journal Histochemistry and Cytochemistry (Monitoring editor)2008-current International Journal of Clinical andExperimental Pathology (IJCEP, ISSN 1936-2625) (Editorial Board)2010 Journal of Alzheimer's Disease (Associate Editor)

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Neuropathology consultant, AVID radiopharmaceuticals 2009-12

    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 trialNeuropathologist 2010-2011

    Research Support, Government Entities:

    1. 1R01AG042210 (Schneider)07/1/12- 06/30/17Epidemiologic Study of TDP-43 Pathology in Aging andDementia Major goal is to determine whether age-related TDP-43pathology represents a separate pathologic processassociated with a dementia syndrome with a distinctcognitive phenotype and specific genetic risk factors thatare separate from AD.Role: Principal investigator

      R01NS078009 (Buchman) 9/15/12-6/30/17 NINDS The Clinical Profile of Parkinson's Disease (PD)Pathology. The overall goal is to characterize the clinical profileof PD pathology in older persons without a diagnosis of PD.Role: co-investigator

      R01AG043379 (Buchman) 9/30/12-8/31/17 NIA Brain and Spinal Cord Microvascular Pathology in Late-LifeMotor ImpairmentThe overall goal is to test the hypothesis that specificmicrovascular pathologies in the brain and spinal cordcontribute to late-life motor impairment.

      U01AG016976 (Kukull/Montine) 7/1/12-6/30/13 NIA (Pilot) Optimization of Neuropathologic Assessment ofAlzheimer's Disease; The overall goal is to optimizeneuropathologic diagnosis of Alzheimer's disease foruniformity and accurancy across centersRole: Site Principal Investigator

      P30 AG10161 (Bennett)9/30/91-6/30/16Rush Alzheimer's Disease Core CenterMajor goals to provide core infrastructure support forresearch regarding aging/dementia/AD. Role: Associate Director, Core Leader: Neuropathology Core

      R01 AG031553 (Morris)3/15/08 - 2/28/13Epidemiologic Study of Brain Vitamin E, Diet, andAge-Related Neurologic Diseases; Major goal is analyzeVitamin E in brain, CSF, serum, and diet and compare toneuropathology and dementia. Role: Co-Principal Investigator

      R01 AG17917 (Bennett)9/30/01-6/30/13Epidemiologic Study of Neural Reserve and Neurobiology ofAging; Major goals are to identify structural bases of reserveand examine mechanisms risk factors lead to age-relatedfunctional impairment.Role: Co-Investigator

      R01 AG15819 (7/1/98 - 6/30/13Risk Factors, Pathology and Clinical Expressions of ADThe major goals of this project are to examine thepathologic mechanisms through which risk factors lead toclinical AD. Role: Co-investigator

      P01 AG14449 (Mufson)9/1/97 - 3/31/13 Neurobiology of Mild cognitive impairment in the Elderly;The major goals are to identify neurobiologic substratesof mild cognitive impairment. Role: Co-investigator (Neuropathologist)

      R01AG033678-01 (Boyle)9/15/2009 - 6/30/14Epidemiologic study of impaired decision making inpreclinical Alzheimer's disease.The overall goal of the proposed epidemiologic study is toexamine the causes and consequences of impaireddecision-making in old age.Role: Neuropathologist

      R01AG034374 (Boyle)8/15/2009 -7/31/14Characterizing the behavior profile of healthy cognitiveaging.Goal is to use innovative statistical approaches tocharacterize the profile of healthy cognitive agingdefined as age-related cognitive change not accounted forby the presence of common neuropathologies (i.e.,Alzheimer's disease, cerebral infarcts, and the Lewy bodydiseases) or terminal decline.Role: Neuropathologist.

      P01 AG09466 (deToledo-Morrell) 4/1/1991-8/31/12 Anatomic, Physiologic, Cognitive Pathology of AD; majorgoals- to identify neurobiologic, radiologic, physiologic,cognitive markers with AD; Role: Co-Investigator; Neuropathologist, Administrative Core

      R01 AG36042 (Bennett)9/15/09-8/31/14Exploring the Role of the Brain Epigenome: CognitiveDecline and Life ExperiencesThe goal of the study is to examine the relation of DNAmethylation to cognitive decline and life experiences.Role: Neuropathologist

      R01 HL096944 (Levine)9/1/09 - 6/30/13Stroke and aPL: Community-Based Clinicopathologic StudyThe major goal of this project is to investigate the roleand mechanisms of antiphospholipid antibodies (aPL) in thedevelopment of pathologically-proven ischemic braininfarction.Role: Neuropathologist

      R01AG040039 (Arvanitakis)9/30/11-8/31/16 NationalInstitute on AgingVascular Cognitive and Motor Decline: Impact of aPLThe major goal of this project is to investigate the roleand mechanisms of antiphospholipid antibodies (aPL) in thedevelopment of cognitive and motor decline in aging.

      R01AG039478 (Arnold)4/1/11-3/31/16 NationalInstitute on AgingTargeted Proteomics of Resilient Cognition in AgingThe major goal of the study is to identify candidateproteins and pathways that best confer cognitiveresilience despite the accumulation of neurodegenerativedisease pathology.Role: Neuropathologist

      R01AG036836 (DeJager)9/15/11-8/31/15 National Institute on AgingExploring the Role of the Brain Transcriptome in CognitiveDeclineThe major goal is to investigate the transcriptome ofhuman brain tissue to identify molecular pathways thatcontribute to cognitive decline. Role: Neuropathologist

    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. David A. Bennett, MD
    8. Scientific Advisory Boards:

    1. (1) Vigorous Minds, Scientific Advisory Board

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Danone, paid for travel to scientific meeting

    Editorial Boards:

    1. (1) Neurology, Editorial Board;(2) Current Alzheimer Research, Editorial Board;(3) Neuroepidemiology, Editorial Board(4) Frontiers Neurology, Editorial Board

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Danone, Inc., (2) Wilmar Schwabe GmbH & Co., (3) Eli Lilly, Inc., (4) the Gerson Lehrman Group

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Danone Inc., PI

    Research Support, Government Entities:

    1. NIH: P30AG10161, PI; R01AG15819, PI; R01AG17917, PI; R01AG36042, PI; U01AG32984, Co-I; R01AG22018, Co-I; R01AG33678, Co-I; R01AG36836, Co-I; R01AG41797, Co-I; R01AG42210, Co-I; and Illinois Department Public Health

    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., P.A.B., S.N., J.A.S., D.A.B.), Neurological Sciences (A.S.B., L.Y., D.A.B.), Behavioral Science (P.A.B.), and Pathology (S.N., J.A.S.), Rush University Medical Center, Chicago, IL; and Departments of Neurology (Stroke Center) and Emergency Medicine (S.R.L.), SUNY Downstate Medical Center, Brooklyn, NY.
  1. Correspondence to Dr. Buchman: Aron_S_Buchman{at}rush.edu
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