Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors

  1. Joshua S Talboom
  2. Asta K Håberg
  3. Matthew D De Both
  4. Marcus A Naymik
  5. Isabelle Schrauwen
  6. Candace R Lewis
  7. Stacy F Bertinelli
  8. Callie Hammersland
  9. Mason A Fritz
  10. Amanda J Myers
  11. Meredith Hay
  12. Carol A Barnes
  13. Elizabeth Glisky
  14. Lee Ryan
  15. Matthew J Huentelman  Is a corresponding author
  1. The Translational Genomics Research Institute, United States
  2. Norwegian University of Science and Technology, Norway
  3. University of Miami, United States
  4. Arizona Alzheimer's Consortium, United States

Abstract

In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer's disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18-85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E ε4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.

Data availability

The data that support the findings of this study are freely available at Dryad (https://datadryad.org) doi:10.5061/dryad.2867k2m.

The following data sets were generated

Article and author information

Author details

  1. Joshua S Talboom

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4327-4103
  2. Asta K Håberg

    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew D De Both

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Marcus A Naymik

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Isabelle Schrauwen

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Candace R Lewis

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Stacy F Bertinelli

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Callie Hammersland

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Mason A Fritz

    The Translational Genomics Research Institute, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Amanda J Myers

    Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Meredith Hay

    Arizona Alzheimer's Consortium, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Carol A Barnes

    Arizona Alzheimer's Consortium, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Elizabeth Glisky

    Arizona Alzheimer's Consortium, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Lee Ryan

    Arizona Alzheimer's Consortium, Phoenix, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Matthew J Huentelman

    The Translational Genomics Research Institute, Phoenix, United States
    For correspondence
    mhuentelman@tgen.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7390-9918

Funding

Mueller Family Charitable Trust

  • Matthew J Huentelman

Arizona DHS in support of the Arizona Alzheimer's Consortium

  • Matthew J Huentelman

Flinn Foundation

  • Matthew J Huentelman

National Institutes of Health (R01- AG041232)

  • Amanda J Myers

National Institutes of Health (R01-AG049465-05)

  • Carol A Barnes

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Muireann Irish, University of Sydney, Australia

Ethics

Human subjects: For all participants, informed consent, and consent to publish was obtained before study participation. This protocol and consent were approved by the Western Institutional Review Board (WIRB, protocol #20111988).

Version history

  1. Received: February 18, 2019
  2. Accepted: June 13, 2019
  3. Accepted Manuscript published: June 18, 2019 (version 1)
  4. Version of Record published: July 9, 2019 (version 2)

Copyright

© 2019, Talboom et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Joshua S Talboom
  2. Asta K Håberg
  3. Matthew D De Both
  4. Marcus A Naymik
  5. Isabelle Schrauwen
  6. Candace R Lewis
  7. Stacy F Bertinelli
  8. Callie Hammersland
  9. Mason A Fritz
  10. Amanda J Myers
  11. Meredith Hay
  12. Carol A Barnes
  13. Elizabeth Glisky
  14. Lee Ryan
  15. Matthew J Huentelman
(2019)
Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors
eLife 8:e46179.
https://doi.org/10.7554/eLife.46179

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https://doi.org/10.7554/eLife.46179

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