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February 04, 2014; 82 (5) Article

Higher RBC EPA + DHA corresponds with larger total brain and hippocampal volumes

WHIMS-MRI Study

James V. Pottala, Kristine Yaffe, Jennifer G. Robinson, Mark A. Espeland, Robert Wallace, William S. Harris
First published January 22, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000080
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Article Information

vol. 82 no. 5 435-442
DOI: 
https://doi.org/10.1212/WNL.0000000000000080
PubMed: 
24453077
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received May 14, 2013
  • Accepted in final form October 24, 2013
  • First Published January 22, 2014.

Article Versions

Copyright & Usage: 
© 2014 American Academy of Neurology

Author Disclosures

    1. James V. Pottala, PhD,
    2. Kristine Yaffe, MD,
    3. Jennifer G. Robinson, MD, MPH,
    4. Mark A. Espeland, PhD,
    5. Robert Wallace, MD, MSc and
    6. William S. Harris, PhD
  1. James V. Pottala, PhD,
    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. (1) OmegaQuant Analytics LLC, Senior Biostatistician, July 2011 - June 2013 (2) Health Diagnostic Laboratory Inc, Principal Biostatistician, June 2013 - present

    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. NHLBI, BAA19, Biostatistician Collaborator, Jan 2009 - Jan 2011

    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. Kristine Yaffe, MD,
    3. Scientific Advisory Boards:

    1. -Novartis, Inc. -DSMB for Takeda, Inc -DSMB for NIH trials - Beeson Advisory Scientific Committee

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. -Associate Editor, 2011-, International Review of Psychiatry -Associate Editor 2012-, Journal of Gerontology: Medical Sciences

    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, NIDDK, NIMH, Department of Defense, California Department of Public Health

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Bright Focus Foundation and Alzheimer Association's

    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. Jennifer G. Robinson, MD, MPH,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Journal of CLinical Lipidology American Journal of Cardiology

    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. Research grants to Institution: Amarin, Amgen, Astra-Zeneca, Daiichi-Sankyo, Esperion, Genetech/Hoffman La Roche, Glaxo-Smith Kline, Merck, Regeneron/Sanofi, Zinfandel/Takeda.

    Research Support, Government Entities:

    1. NIH, AHRQ, FDA

    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. Mark A. Espeland, PhD,
    5. Scientific Advisory Boards:

    1. Terumo Medical Corporation -- DSMB board KOWA Research Institute -- DSMB Board Boehringer-Ingelheim -- Advisory Board Takeda Global Research-- Advisory Board

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. The Journals of Gerontology Medical Sciences, Statistical Editor, 2012 through present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Wake Forest School of Medicine

    Consultancies:

    1. Non-Profit entity: I serve on several monitoring boards for NIH studies.

    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. D. Research Support Active Research Support U01 DK57136 (Espeland) 09/01/1999 � 07/31/2013 NIDDK Look AHEAD: Action for Health in Diabetes Data Coordinating Center Look AHEAD is a multi center randomized trial designed to test whether weight loss interventions can reduce the progression of carotid atherosclerosis and other health outcomes in a cohort of 5145 obese/overweight type 2 diabetics. Role: Principal Investigator NHLBI (Shumaker) 11/01/2010 � 06/30/2011 WHIMS MRI 2B WHIMS-MRI-2 will assess whether changes in total and regional brain volumes over time will be greater among women who had been assigned to active therapy during the WHI HT trials and will contrast the mean changes in volume, relative to placebo, for the CEE-Alone and CEE+MPA therapies, after adjustment for length of time between scans, intracranial volume, and age. Role: Co-Investigator NHLBI (Harris) 01/15/2009 � 01/14/2011 Omega-3 Fatty Acid Biomarkers and Cognitive Decline in WHIMS This is a subcontract between WFUHS and the University of South Dakota. WFUHS will analyze data from the 1400 samples from the WHIMS-MRI study and data from the WHISCA study. Role: Principal Investigator of subcontract R01 AG033087 (Kritchevsky) 09/30/2009 � 08/31/2014 NIA Intentional Weight Reduction and Physical and Cognitive Function This ancillary study of the Action for Health in Diabetes trial will determine: 1) the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on physical function; 2) the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on cognitive function; and 3) whether inflammatory biomarkers mediate the association between the lifestyle intervention and physical and cognitive function. Role: Co-Investigator R01 HL090875-01A1 (Espeland) 08/18/2009 � 05/31/2014 NHLBI SNAP: Preventing Weight Gain in Young Adults This project is a multi-center randomized trial designed to test whether two behavioral interventions can prevent weight gain in young adults as compared to control groups. WFUHS will serve as the Data Coordinating Center. Role: Principal Investigator U01 AG022376 (Pahor) 09/01/2009 � 08/31/2015 NIA Physical Exercise to Prevent Disability (Life-M) This proposal project represents a subcontract with the University of Florida. Wake Forest University will serve as the Data Management, Analysis and Quality Control for this study. The major goal of this project is to provide definite evidence in the use of physical exercise to prevent physical and mobility disability in older persons. Role: Co-Principal Investigator of Subcontract R21 CA139291-01 (Tooze) 07/01/2009 � 06/30/2011 NCI Development and Application of Measurement Error Models This study will provide statistical methods for correcting physical activity data for measurement error in an epidemiologic study. It will provide insight as to whether the Actigraph may be used as an unbiased measure, and provide a statistical modeling approach for assessing other accelerometers in other studies. Role: Co-Investigator 2P01HL051952-16 (Ferrario) 04/01/2009 � 03/31/2014 NHLBI Vasodepressor Mechanisms in Hypertension This research will pursue the overall hypothesis that hypertension and aging, as well as impaired cardiac, renal, vascular and metabolic function, reflect the complex imbalance in the expression of the ACE2/Ang-(1-7)/mas-receptor axis and the ACE/Ang II/AT1 pathway in multiple tissues. Role: Co-Investigator NHLBI-WH-11-10 (Shumaker) 10/01/2010 � 09/30/2015 NIH Women�s Health Initiative Extension 2010-2015: The Southeast Regional Center WFUHS will serve as the Southeast Regional Center for the Women�s Health Initiative (WHI). The regional center will work with the WHI central coordinating center to collect study outcomes and maintain the study participants from 9 former WHI clinical centers in the southeastern US; assist investigators to publish papers from the study data and develop and conduct ancillary studies. Role: Co-Principal Investigator WH-4-4221 (Shumaker) 11/01/2010 � 04/30/2011 NHLBI WHIMS ECHO B WHIMS ECHO B will model rates and correlates of transitions among cognitively normal, MCI, and PD women over time; examine the predictive ability of the domain-specific WHISCA cognitive battery for subsequent incidence of MCI and PD; and examine the progression of specific subtypes of cognitive deficits and impairment. Role: Co-Investigator (Shumaker) 11/01/2010 � 04/30/2011 NHLBI WHIMSY B WHIMSY will test whether prior random assignment to hormone therapy (E-alone or E+P) has long-term effects on women�s cognitive function. Secondary objectives relate to the consistency of any treatment effects across unopposed or opposed therapy and whether there exists evidence of graded relationships between cognitive effects and age. Role: Co-Investigator Completed Research Support N01 AG92115 (Shumaker) 07/01/1999 � 06/30/2010 NIA (No-cost extension) The Effects of Hormone Replacement Therapy on Cognitive Aging: Women�s Health Initiative Study on Cognitive Aging (WHISCA) The objectives of WHISCA are to assess the effects of hormone replacement therapy on cognitive aging and selected non-demented women. Role: Co-Principal Investigator N01AG12106 (Shumaker) 04/06/01 � 03/31/2009 NIA Effects of Selective Estrogen Receptor Modulators on Cognitive Aging Cognition in the Study of Tamoxifen and Raloxifene � (Co-STAR) The objectives of CoSTAR are to assess the effects of tamoxifen and raloxifene on cognition among women aged 65 years and older. Role: Co-Investigator R01HL085323 (Ding) 07/01/06 � 06/30/10 NHLBI Pericardial Fat and Subclinical and Clinical Measures of Coronary Heart Disease This study assessed associations that fat measures from imaging studies have with coronary heart disease and CVD risk factors. Role: Co-Investigator Active Research Support U01 AG022376 (Pahor) 09/01/2009 � 08/31/2015 NIA The LIFE Study This project represents a subcontract with the University of Florida. Wake Forest University serves as the Data Management, Analysis and Quality Control for this study. The major goal of this project is to provide definite evidence in the use of physical exercise to prevent physical and mobility disability in older persons. Role: Co-Principal Investigator of DMAQC U01 DK57136 (Espeland) 09/01/1999 � 07/31/2013 NIDDK Look AHEAD: Action for Health in Diabetes Data Coordinating Center Look AHEAD is a multi-center randomized trial designed to test whether weight loss interventions can reduce the progression of carotid atherosclerosis and other health outcomes in a cohort of 5145 obese/overweight type 2 diabetics. Role: Principal Investigator R01 AG033087 (Kritchevsky) 09/30/2009 � 08/31/2014 NIA Intentional Weight Reduction and Physical and Cognitive Function This project is an ancillary study of the Look AHEAD (Action for Health in Diabetes) trial. The specific aims are: 1) to determine the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on physical function; 2) to determine the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on cognitive function; and 3) to determine whether inflammatory biomarkers mediate the association between the lifestyle intervention and physical and cognitive function. Role: Co-Investigator R01 HL090875-01A1 (Espeland) 08/18/2009 � 05/31/2014 NHLBI SNAP: Preventing Weight Gain in Young Adults This project is a multi-center randomized trial designed to test whether two behavioral interventions can prevent weight gain in young adults as compared to control groups. WFUHS will serve as the Data Coordinating Center. Role: Principal Investigator HHSN271201100004C (Shumaker) 05/06/2011 � 05/05/2016 NIH Hormone Therapy and Cognitive Aging in Older and Younger Postmenopausal Women: Extension Study of WHIMS-ECHO WHIMS-ECHO extended follow-up will increase the total cases of probable dementia and cognitive impairment thereby enhancing the scientific value of the program by providing the statistical power necessary to: 1. Characterize how women transition among cognitive states; 2. Identify subtypes of cognitive deficit/impairment; and 3. Identify predictors related to cognitive health and decline. Role: Co-Investigator/Biostatistician HHSN271201100004C (Shumaker) 05/06/2011 � 05/05/2016 NHLBI Hormone Therapy and Cognitive Aging in Older and Younger Postmenopausal Women: Extension of WHIMS-Y WHIMS-ECHO extended follow-up will increase the total cases of probable dementia and cognitive impairment thereby enhancing the scientific value of the program by providing the statistical power necessary to: 1. Characterize how women transition among cognitive states; 2. Identify subtypes of cognitive deficit/impairment; and. 3. Identify predictors related to cognitive health and decline. Role: Co-Investigator 1R01AG33078-01A2 (Chen) 03/15/2011 � 02/28/2015 NIA Environmental Determinants of Cognitive Aging in the Women's Health Initiative Memory Study This is a sub-contract with University of Southern California, Keck School of Medicine. This study aims to investigate ambient air pollutants as novel environmental determinants of cognitive aging in elderly women. Role: Co-Investigator 1P60MD006917-01 (A. Bertoni) 8/1/2012 � 2/28/2017 NIH Translating Lifestyle Intervention into the Community and Clinic for Diabetes The overall goal of �Translating Lifestyle intervention into the Clinic and Community for Diabetes� (TLCC Diabetes) is to investigate two approaches to delivering an intervention designed to improve diabetes control among minority and lower-income patients with diabetes. Role: Co-Investigator NHLBI-WH-11-10 (Shumaker) 10/01/2010 � 09/30/2015 NIH Women�s Health Initiative Extension 2010-2015: The Southeast Regional Center WFUHS will serve as the Southeast Regional Center for the Women�s Health Initiative (WHI). The regional center will work with the WHI central coordinating center to collect study outcomes and maintain the study participants from 9 former WHI clinical centers in the southeastern US; assist investigators to publish papers from the study data and develop and conduct ancillary studies. Role: Co-Principal Investigator 1R01DK092237 (Espeland) 09/15/2011 � 08/31/2016 NIDDK Action for Health in Diabetes Brain Magnetic Resonance Imaging Ancillary Study The goal of this project is the care of adults with type 2 diabetes mellitus, who are at increased risk for atrophy, cerebrovascular disease, and cognitive impairment. Role: Principal Investigator R01DK092237-02S2 (Espeland) 09/01/2012 � 08/31/2013 NIDDK Action for Health in Diabetes Brain MRI Ancillary Study Supplement #2 The goal of this project is to extend the scientific aims of Look AHEAD Brain by adding novel MRI measures and NIH toolbox assessments of cognitive function and increasing the data available for longitudinal and subgroup analyses of cognitive and physical function. Role: Principal Investigator R01 AG033087-04S1 (Kritchevsky) 10/01/2012 � 08/31/2013 NIA Intentional Weight Reduction and Physical and Cognitive Function Supplement The goals of this project are to collect additional cognitive and physical function data from Look AHEAD (Action for Health in Diabetes) participants at the Year 10/11 visit in the Baton Rouge, Memphis and Denver field sites to examine whether random assignment to an intensive lifestyle intervention benefits changes in function in overweight/obese middle aged and older adults with type 2 diabetes. Role: 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

  5. Robert Wallace, MD, MSc and
    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. Merck and Co.: Clinical trial safety monitoring Novartis Pharm: Clinical trial safety monitoring

    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. National Institutes of Health

    Research Support, Academic Entities:

    1. University of Texas at Austin University of Texas Galveston University of Michigan

    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. William S. Harris, PhD
    7. Scientific Advisory Boards:

    1. Aker Biomarine Antarctica 2011-present Omthera Pharmaceuticals 2011-present

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Speak often to physician groups as part of my job working for Health Diagnostic Laboratory, Inc.

    Editorial Boards:

    1. NONE

    Patents:

    1. Methods for assessing risk for acute coronary syndromes using red blood cell fatty acid patterns

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Health Diagnostic Laboratory, Inc. Sr. Research Scientist

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. Founder and President of Omegaquant Analytics, LLC.

    Clinical Procedures or Imaging Studies:

    1. If RBC omega-3 had been shown in this study to predict baseline or a change in cognitive function, then it is possible that more doctors would be interested in ordering the test which is offered by Health Diagnostic Laboratory.

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. Omegaquant analyzed RBC fatty acid levels for Dr. Raymond Kwong at the Brigham and Women's Hospital on his NIH study on cardiac MRI and fish oil.

    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 Department of Internal Medicine (J.V.P., W.S.H.), Sanford School of Medicine, University of South Dakota, Sioux Falls; Health Diagnostic Laboratory Inc. (J.V.P., W.S.H.), Richmond, VA; Department of Psychiatry (K.Y.), University of California Medical Center, San Francisco; Departments of Epidemiology and Internal Medicine (J.R., R.W.), University of Iowa College of Public Health, Iowa City; Department of Biostatistical Services (M.A.E.), Wake Forest School of Medicine, Winston-Salem, NC; and OmegaQuant Analytics (W.S.H.), Sioux Falls, SD.
  1. Correspondence to Dr. Pottala: jpottala{at}hdlabinc.com

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