TY - JOUR T1 - Semantic Fluency Predicts Six-Year Progression to Mild Cognitive Impairment in Middle-Aged Men JF - bioRxiv DO - 10.1101/659417 SP - 659417 AU - Daniel E. Gustavson AU - Jeremy A. Elman AU - Matthew S. Panizzon AU - Carol E. Franz AU - Jordan Zuber AU - Mark Sanderson-Cimino AU - Chandra A. Reynolds AU - Kristen C. Jacobson AU - Hong Xian AU - Amy J. Jak AU - Rosemary Toomey AU - Michael J. Lyons AU - William S. Kremen Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/04/659417.abstract N2 - 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 1484 male twins, 842 of whom were cognitively normal at wave 1 completed measures of episodic memory and verbal fluency at up to 2 time-points (mean age 56 and 62 years).Results In the subgroup of 842, 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 phonemic 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 These findings emphasize the utility of memory and fluency measures in early identification of AD risk. 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 of 6-year change in memory as well as progression to amnestic MCI even after accounting for baseline memory performance. ER -