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Baseline Semantic Fluency Is Associated with Six-Year Progression to Mild Cognitive Impairment in Middle-Aged Men

Daniel E. Gustavson, View ORCID ProfileJeremy A. Elman, Matthew S. Panizzon, Carol E. Franz, Jordan Zuber, Mark Sanderson-Cimino, Chandra A. Reynolds, Kristen C. Jacobson, Hong Xian, Amy J. Jak, Rosemary Toomey, Michael J. Lyons, William S. Kremen
doi: https://doi.org/10.1101/659417
Daniel E. Gustavson
1st, Nashville, TN 37232. Phone: 303-748-0627. E-mail:
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  • For correspondence: dgustavson@ucsd.edu daniel.e.gustavson@vumc.org
Jeremy A. Elman
2Department of Psychiatry, Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA
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  • ORCID record for Jeremy A. Elman
Matthew S. Panizzon
2Department of Psychiatry, Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA
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Carol E. Franz
2Department of Psychiatry, Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA
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Jordan Zuber
2Department of Psychiatry, Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA
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Mark Sanderson-Cimino
2Department of Psychiatry, Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA
3Department of Psychology, San Diego State University, San Diego, CA
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Chandra A. Reynolds
4Department of Psychology, University of California, Riverside, Riverside, CA
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Kristen C. Jacobson
5Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL
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Hong Xian
6Department of Epidemiology and Biostatistics, St. Louis University and Clinical Epidemiology Center, Veterans Affairs St. Louis Healthcare System, St. Louis, MO
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Amy J. Jak
7Department of Psychiatry, University of California, San Diego, La Jolla, CA and Psychology Service and Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, La Jolla, CA
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Rosemary Toomey
8Department of Psychological and Brain Sciences, Boston University, Boston, MA
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Michael J. Lyons
8Department of Psychological and Brain Sciences, Boston University, Boston, MA
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William S. Kremen
9Department of Psychiatry, Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA and Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, La Jolla, CA
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Abstract

Objective Test the hypothesis that individual differences in episodic memory and verbal fluency in cognitively normal middle-aged adults will predict progression to amnestic MCI after 6 years.

Method The analysis sample included 842 male twins who were cognitively normal at baseline (M=56 years), completed measures of episodic memory and verbal fluency at baseline and again 6 years later (M=62 years).

Results Poor episodic memory predicted progression to both amnestic MCI (OR=4.42, 95% CI [2.44, 10.60]) and non-amnestic MCI (OR=1.92, 95% CI [1.32, 3.44]). Poor semantic verbal fluency also independently predicted progression to amnestic MCI (OR=1.86, 95% CI [1.12, 3.52]). In the full sample, a semantic-specific fluency latent variable at wave 1 (which controls for letter fluency) predicted change in episodic memory at wave 2 (β=.13), but not vice-versa (β=.04). Associations between episodic memory and verbal fluency factors were primarily explained by genetic, rather than environmental, correlations.

Conclusions Among individuals who were cognitively normal at wave 1, episodic memory moderately-to-strongly predicted progression to MCI at average age 62, emphasizing the fact that there is still meaningful variability even among cognitively normal individuals. Episodic memory, which is typically a primary focus for AD risk, declined earlier and more quickly than fluency. However, semantic fluency at average age 56 predicted 6-year change in memory as well as progression to amnestic MCI even after accounting for baseline memory performance. These findings emphasize the utility of memory and fluency measures in early identification of AD risk.

Footnotes

  • Revisions were made based on initial peer review of the work. Revisions include additional methodological information, supplementary analyses, and minor changes to introduction and discussion.

Copyright 
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 September 11, 2019.
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Baseline Semantic Fluency Is Associated with Six-Year Progression to Mild Cognitive Impairment in Middle-Aged Men
Daniel E. Gustavson, Jeremy A. Elman, Matthew S. Panizzon, Carol E. Franz, Jordan Zuber, Mark Sanderson-Cimino, Chandra A. Reynolds, Kristen C. Jacobson, Hong Xian, Amy J. Jak, Rosemary Toomey, Michael J. Lyons, William S. Kremen
bioRxiv 659417; doi: https://doi.org/10.1101/659417
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Baseline Semantic Fluency Is Associated with Six-Year Progression to Mild Cognitive Impairment in Middle-Aged Men
Daniel E. Gustavson, Jeremy A. Elman, Matthew S. Panizzon, Carol E. Franz, Jordan Zuber, Mark Sanderson-Cimino, Chandra A. Reynolds, Kristen C. Jacobson, Hong Xian, Amy J. Jak, Rosemary Toomey, Michael J. Lyons, William S. Kremen
bioRxiv 659417; doi: https://doi.org/10.1101/659417

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