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

By 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

Posted 04 Jun 2019
bioRxiv DOI: 10.1101/659417

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.

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