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Reproducibility of the correlative triad among aging, dopamine receptor availability, and cognition

View ORCID ProfileEric J. Juarez, View ORCID ProfileJaime J. Castrellon, View ORCID ProfileMikella A. Green, Jennifer L. Crawford, View ORCID ProfileKendra L. Seaman, View ORCID ProfileChristopher T. Smith, View ORCID ProfileLinh C. Dang, David Matuskey, Evan D. Morris, Ronald L. Cowan, View ORCID ProfileDavid H. Zald, View ORCID ProfileGregory R. Samanez-Larkin
doi: https://doi.org/10.1101/494765
Eric J. Juarez
1Department of Psychology and Neuroscience, Duke University
2Center for Cognitive Neuroscience, Duke University
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  • For correspondence: eric.juarez@duke.edu
Jaime J. Castrellon
1Department of Psychology and Neuroscience, Duke University
2Center for Cognitive Neuroscience, Duke University
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Mikella A. Green
1Department of Psychology and Neuroscience, Duke University
2Center for Cognitive Neuroscience, Duke University
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Jennifer L. Crawford
3Department of Psychology, Yale University
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Kendra L. Seaman
2Center for Cognitive Neuroscience, Duke University
4Center for the Study of Aging and Human Development, Duke University
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Christopher T. Smith
5Department of Psychology, Vanderbilt University
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Linh C. Dang
5Department of Psychology, Vanderbilt University
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David Matuskey
6Department of Radiology and Biomedical Imaging, Yale University
7Department of Psychiatry, Yale University
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Evan D. Morris
6Department of Radiology and Biomedical Imaging, Yale University
7Department of Psychiatry, Yale University
8Department of Biomedical Engineering, Yale University
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Ronald L. Cowan
5Department of Psychology, Vanderbilt University
9Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine
10Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center
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David H. Zald
5Department of Psychology, Vanderbilt University
9Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine
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Gregory R. Samanez-Larkin
1Department of Psychology and Neuroscience, Duke University
2Center for Cognitive Neuroscience, Duke University
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Abstract

The evidence that dopamine function mediates the association between aging and cognition is one of the most cited findings in the cognitive neuroscience of aging. However, few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) availability, and cognition in two cross-sectional studies of healthy human adults. Subjects completed a short cognitive test battery and, on a separate day, a PET scan with either the high-affinity D2R tracer [18F]Fallypride (Study 1) or [11C]FLB457 (Study 2). Digit span, a measure of short-term memory maintenance and working memory, was the only cognitive test for which dopamine D2R availability partially mediated the age effect on cognition. In Study 1, age was negatively correlated with digit span. Striatal D2R availability was positively correlated with digit span controlling for age. The age effect on digit span was smaller when controlling for striatal D2R availability. Although other cognitive measures used here have individually been associated with age and D2R availability in prior studies, we found no consistent evidence for significant associations between low D2R availability and low cognitive performance on these measures. These results at best only partially supported the correlative triad of age, dopamine D2R availability, and cognition. While a wealth of other research in human and non-human animals demonstrates that dopamine makes critical contributions to cognition, the present studies suggest caution in using PET measures as evidence that dopamine D2R loss specifically is a primary cause of broad age-related declines in fluid cognition.

Footnotes

  • Author Note: Jennifer Crawford is now at Washington University in St Louis. Kendra Seaman is now at University of Texas Dallas. Christopher T. Smith is now at North Carolina State University. Linh Dang is now at Google. Some of the results reported in this manuscript were presented in a poster at the Cognitive Neuroscience Society annual meeting (2018) and the Cognitive Aging Conference (2018). Correspondence concerning this article should be addressed to Eric Juarez, Department of Psychology and Neuroscience, Duke University, Box 90999, Durham, NC 27708. Email: eric.juarez{at}duke.edu

  • https://osf.io/xjqe9/

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 17, 2019.
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Reproducibility of the correlative triad among aging, dopamine receptor availability, and cognition
Eric J. Juarez, Jaime J. Castrellon, Mikella A. Green, Jennifer L. Crawford, Kendra L. Seaman, Christopher T. Smith, Linh C. Dang, David Matuskey, Evan D. Morris, Ronald L. Cowan, David H. Zald, Gregory R. Samanez-Larkin
bioRxiv 494765; doi: https://doi.org/10.1101/494765
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Reproducibility of the correlative triad among aging, dopamine receptor availability, and cognition
Eric J. Juarez, Jaime J. Castrellon, Mikella A. Green, Jennifer L. Crawford, Kendra L. Seaman, Christopher T. Smith, Linh C. Dang, David Matuskey, Evan D. Morris, Ronald L. Cowan, David H. Zald, Gregory R. Samanez-Larkin
bioRxiv 494765; doi: https://doi.org/10.1101/494765

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