Daniel E Gustavson1, Jeremy A Elman1, Matthew S Panizzon1, Carol E Franz1, Jordan Zuber1, Mark Sanderson-Cimino1, Chandra A Reynolds1, Kristen C Jacobson1, Hong Xian1, Amy J Jak1, Rosemary Toomey1, Michael J Lyons1, William S Kremen1. 1. From the Department of Psychiatry (A.J.J.), Center for Behavior Genetics of Aging (D.E.G., J.A.E., M.S.P., C.E.F., J.Z., M.S.-C., W.S.K.), University of California, San Diego, La Jolla; Department of Medicine (D.E.G.), Vanderbilt University Medical Center, Nashville, TN; Department of Psychology (M.S.-C.), San Diego State University; Department of Psychology (C.A.R.), University of California; Department of Psychiatry and Behavioral Neuroscience (K.C.J.), University of Chicago, IL; Department of Epidemiology and Biostatistics (H.X.), St. Louis University; Clinical Epidemiology Center (H.X.), Veterans Affairs St. Louis Healthcare System, MO; Psychology Service (A.J.J.) and Center of Excellence for Stress and Mental Health (A.J.J., W.S.K.), Veterans Affairs San Diego Healthcare System, CA; and Department of Psychological and Brain Sciences (R.T., M.J.L.), Boston University, MA.
Abstract
OBJECTIVE: To test the hypothesis that individual differences in episodic memory and verbal fluency in cognitively normal middle-aged adults will predict progression to amnestic mild cognitive impairment (MCI) after 6 years. METHOD: The cohort analyzed included 842 male twins who were cognitively normal at baseline (mean 56 years) and completed measures of episodic memory and verbal fluency at baseline and again 6 years later (mean 62 years). RESULTS: Poor episodic memory predicted progression to both amnestic MCI (odds ratio [OR], 4.42; 95% confidence interval [CI], 2.44-10.60) and nonamnestic 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 = 0.13), but not vice versa (β = 0.04). 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 Alzheimer disease (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.
OBJECTIVE: To test the hypothesis that individual differences in episodic memory and verbal fluency in cognitively normal middle-aged adults will predict progression to amnestic mild cognitive impairment (MCI) after 6 years. METHOD: The cohort analyzed included 842 male twins who were cognitively normal at baseline (mean 56 years) and completed measures of episodic memory and verbal fluency at baseline and again 6 years later (mean 62 years). RESULTS: Poor episodic memory predicted progression to both amnestic MCI (odds ratio [OR], 4.42; 95% confidence interval [CI], 2.44-10.60) and nonamnestic 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 = 0.13), but not vice versa (β = 0.04). 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 Alzheimer disease (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.
Authors: Daniel E Gustavson; Matthew S Panizzon; Carol E Franz; Chandra A Reynolds; Robin P Corley; John K Hewitt; Michael J Lyons; William S Kremen; Naomi P Friedman Journal: J Exp Psychol Gen Date: 2019-03-21
Authors: Daniel E Gustavson; Matthew S Panizzon; Jeremy A Elman; Carol E Franz; Asad Beck; Chandra A Reynolds; Kristen C Jacobson; Hong Xian; Rosemary Toomey; Michael J Lyons; William S Kremen Journal: Behav Genet Date: 2018-06-19 Impact factor: 2.805
Authors: Amy J Jak; Matthew S Panizzon; Kelly M Spoon; Christine Fennema-Notestine; Carol E Franz; Wesley K Thompson; Kristen C Jacobson; Hong Xian; Lisa T Eyler; Eero Vuoksimaa; Rosemary Toomey; Michael J Lyons; Michael C Neale; Ming T Tsuang; Anders M Dale; William S Kremen Journal: Am J Geriatr Psychiatry Date: 2014-08-29 Impact factor: 4.105
Authors: Clifford R Jack; David A Bennett; Kaj Blennow; Maria C Carrillo; Billy Dunn; Samantha Budd Haeberlein; David M Holtzman; William Jagust; Frank Jessen; Jason Karlawish; Enchi Liu; Jose Luis Molinuevo; Thomas Montine; Creighton Phelps; Katherine P Rankin; Christopher C Rowe; Philip Scheltens; Eric Siemers; Heather M Snyder; Reisa Sperling Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: Mark W Logue; Matthew S Panizzon; William S Kremen; Jeremy A Elman; Nathan A Gillespie; Sean N Hatton; Daniel E Gustavson; Ole A Andreassen; Anders M Dale; Carol E Franz; Michael J Lyons; Michael C Neale; Chandra A Reynolds; Xin Tu Journal: Mol Psychiatry Date: 2018-02-27 Impact factor: 15.992
Authors: Jeremy A Elman; Amy J Jak; Matthew S Panizzon; Xin M Tu; Tian Chen; Chandra A Reynolds; Daniel E Gustavson; Carol E Franz; Sean N Hatton; Kristen C Jacobson; Rosemary Toomey; Ruth McKenzie; Hong Xian; Michael J Lyons; William S Kremen Journal: Alzheimers Dement (Amst) Date: 2018-05-14
Authors: Daniel E Gustavson; Chandra A Reynolds; Timothy J Hohman; Angela L Jefferson; Jeremy A Elman; Matthew S Panizzon; Michael C Neale; Mark W Logue; Michael J Lyons; Carol E Franz; William S Kremen Journal: J Int Neuropsychol Soc Date: 2022-02-21 Impact factor: 3.114