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).
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
Further reading
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Background: Several fields have described low reproducibility of scientific research and poor accessibility in research reporting practices. Although previous reports have investigated accessible reporting practices that lead to reproducible research in other fields, to date, no study has explored the extent of accessible and reproducible research practices in cardiovascular science literature.
Methods: To study accessibility and reproducibility in cardiovascular research reporting, we screened 639 randomly selected articles published in 2019 in three top cardiovascular science publications: Circulation, the European Heart Journal, and the Journal of the American College of Cardiology (JACC). Of those 639 articles, 393 were empirical research articles. We screened each paper for accessible and reproducible research practices using a set of accessibility criteria including protocol, materials, data, and analysis script availability, as well as accessibility of the publication itself. We also quantified the consistency of open research practices within and across cardiovascular study types and journal formats.
Results: We identified that fewer than 2% of cardiovascular research publications provide sufficient resources (materials, methods, data, and analysis scripts) to fully reproduce their studies. Of the 639 articles screened, 393 were empirical research studies for which reproducibility could be assessed using our protocol, as opposed to commentaries or reviews. After calculating an accessibility score as a measure of the extent to which an article makes its resources available, we also showed that the level of accessibility varies across study types with a score of 0.08 for Case Studies or Case Series and 0.39 for Clinical Trials (p = 5.500E-5) and across journals (0.19 through 0.34, p = 1.230E-2). We further showed that there are significant differences in which study types share which resources.
Conclusion: Although the degree to which reproducible reporting practices are present in publications varies significantly across journals and study types, current cardiovascular science reports frequently do not provide sufficient materials, protocols, data, or analysis information to reproduce a study. In the future, having higher standards of accessibility mandated by either journals or funding bodies will help increase the reproducibility of cardiovascular research.
Funding: Authors Gabriel Heckerman, Arely Campos-Melendez, and Chisomaga Ekwueme were supported by an NIH R25 grant from the National Heart, Lung and Blood Institute (R25HL147666). Eileen Tzng was supported by an AHA Institutional Training Award fellowship (18UFEL33960207).
