Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors
- The Translational Genomics Research Institute, United States
- Norwegian University of Science and Technology, Norway
- University of Miami, United States
- 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.
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Data from: Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factorsDryad Digital Repository, doi:10.5061/dryad.j1fd7.
Article and author information
Author details
Matthew J Huentelman
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.
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).
Reviewing Editor
- Muireann Irish, University of Sydney, Australia
Version history
- Received: February 18, 2019
- Accepted: June 13, 2019
- Accepted Manuscript published: June 18, 2019 (version 1)
- 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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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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