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March 26, 2013; 80 (13) Article

Neural reserve, neuronal density in the locus ceruleus, and cognitive decline

Robert S. Wilson, Sukriti Nag, Patricia A. Boyle, Loren P. Hizel, Lei Yu, Aron S. Buchman, Julie A. Schneider, David A. Bennett
First published March 13, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182897103
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Article Information

vol. 80 no. 13 1202-1208
DOI: 
https://doi.org/10.1212/WNL.0b013e3182897103
PubMed: 
23486878
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received September 26, 2012
  • Accepted November 26, 2012
  • First Published March 13, 2013.

Article Versions

Copyright & Usage: 
© 2013 American Academy of Neurology

Author Disclosures

    1. Robert S. Wilson, PhD,
    2. Sukriti Nag, MD, PhD,
    3. Patricia A. Boyle, PhD,
    4. Loren P. Hizel, BA,
    5. Lei Yu, PhD,
    6. Aron S. Buchman, MD,
    7. Julie A. Schneider, MD and
    8. David A. Bennett, MD
  1. Robert S. Wilson, PhD,
    2. 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

    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 R01AG024871, PI, 2006-2011; (2) NIH/NIA P30AG10161, Co-I, 1991-2011; (3) NIH/NIA R01AG11101, Co-I, 1993-2011; (4) NIH/NIA R01AG15819, Co-I, 1998-2013

    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

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

  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. (1) NIH/NIA R01AG034374, PI; (2) NIH/NIA R01AG033678, 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

  4. Loren P. Hizel, BA,
    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. NONE

    Research Support, Government Entities:

    1. (1) NIH/NIA, R01AG017917 & P30AG10161, research assistant, 2010-2012

    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. Lei Yu, 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. 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

  6. Aron S. Buchman, MD,
    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. (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

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

    1. 1. served on scientific advisory board for GE Healthcare (2010), 2. served on scientific advisory board for Eli Lilly and Company (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 and Experimental 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 trial Neuropathologist 2010-2011

    Research Support, Government Entities:

    1. 1R01AG042210 (Schneider) 07/1/12- 06/30/17 Epidemiologic Study of TDP-43 Pathology in Aging and Dementia Major goal is to determine whether age-related TDP-43 pathology represents a separate pathologic process associated with a dementia syndrome with a distinct cognitive phenotype and specific genetic risk factors that are 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 profile of 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-Life Motor Impairment The overall goal is to test the hypothesis that specific microvascular pathologies in the brain and spinal cord contribute to late-life motor impairment. U01AG016976 (Kukull/Montine) 7/1/12-6/30/13 NIA (Pilot) Optimization of Neuropathologic Assessment of Alzheimer's Disease; The overall goal is to optimize neuropathologic diagnosis of Alzheimer's disease for uniformity and accurancy across centers Role: Site Principal Investigator P30 AG10161 (Bennett) 9/30/91-6/30/16 Rush Alzheimer's Disease Core Center Major goals to provide core infrastructure support for research regarding aging/dementia/AD. Role: Associate Director, Core Leader: Neuropathology Core R01 AG031553 (Morris) 3/15/08 - 2/28/13 Epidemiologic Study of Brain Vitamin E, Diet, and Age-Related Neurologic Diseases; Major goal is analyze Vitamin E in brain, CSF, serum, and diet and compare to neuropathology and dementia. Role: Co-Principal Investigator R01 AG17917 (Bennett) 9/30/01-6/30/13 Epidemiologic Study of Neural Reserve and Neurobiology of Aging; Major goals are to identify structural bases of reserve and examine mechanisms risk factors lead to age-related functional impairment. Role: Co-Investigator R01 AG15819 (7/1/98 - 6/30/13 Risk Factors, Pathology and Clinical Expressions of AD The major goals of this project are to examine the pathologic mechanisms through which risk factors lead to clinical 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 substrates of mild cognitive impairment. Role: Co-investigator (Neuropathologist) R01AG033678-01 (Boyle) 9/15/2009 - 6/30/14 Epidemiologic study of impaired decision making in preclinical Alzheimer's disease. The overall goal of the proposed epidemiologic study is to examine the causes and consequences of impaired decision-making in old age. Role: Neuropathologist R01AG034374 (Boyle) 8/15/2009 -7/31/14 Characterizing the behavior profile of healthy cognitive aging. Goal is to use innovative statistical approaches to characterize the profile of healthy cognitive aging defined as age-related cognitive change not accounted for by the presence of common neuropathologies (i.e., Alzheimer's disease, cerebral infarcts, and the Lewy body diseases) or terminal decline. Role: Neuropathologist. P01 AG09466 (deToledo-Morrell) 4/1/1991-8/31/12 Anatomic, Physiologic, Cognitive Pathology of AD; major goals- to identify neurobiologic, radiologic, physiologic, cognitive markers with AD; Role: Co-Investigator; Neuropathologist, Administrative Core R01 AG36042 (Bennett) 9/15/09-8/31/14 Exploring the Role of the Brain Epigenome: Cognitive Decline and Life Experiences The goal of the study is to examine the relation of DNA methylation to cognitive decline and life experiences. Role: Neuropathologist R01 HL096944 (Levine) 9/1/09 - 6/30/13 Stroke and aPL: Community-Based Clinicopathologic Study The major goal of this project is to investigate the role and mechanisms of antiphospholipid antibodies (aPL) in the development of pathologically-proven ischemic brain infarction. Role: Neuropathologist R01AG040039 (Arvanitakis) 9/30/11-8/31/16 National Institute on Aging Vascular Cognitive and Motor Decline: Impact of aPL The major goal of this project is to investigate the role and mechanisms of antiphospholipid antibodies (aPL) in the development of cognitive and motor decline in aging. R01AG039478 (Arnold) 4/1/11-3/31/16 National Institute on Aging Targeted Proteomics of Resilient Cognition in Aging The major goal of the study is to identify candidate proteins and pathways that best confer cognitive resilience despite the accumulation of neurodegenerative disease pathology. Role: Neuropathologist R01AG036836 (DeJager) 9/15/11-8/31/15 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. 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

  8. David A. Bennett, MD
    9. 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 and Departments of Neurological Sciences (R.S.W., L.Y., A.S.B., J.A.S., D.A.B.), Behavioral Sciences (R.S.W., P.A.B.), and Pathology (S.N., J.A.S.), Rush University Medical Center (L.P.H.), Chicago, IL.
  1. Correspondence to Dr. Wilson: rwilson{at}rush.edu
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