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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.
Glossary
- AD=
- Alzheimer disease;
- CFI=
- comparative fit index;
- CI=
- confidence interval;
- CN=
- cognitively normal;
- CVLT=
- California Verbal Learning Test II;
- DZ=
- dizygotic;
- LM=
- logical memory;
- MCI=
- mild cognitive impairment;
- MZ=
- monozygotic;
- OR=
- odds ratio;
- RMSEA=
- root mean square error of approximation;
- VETSA=
- Vietnam Era Twin Study of Aging;
- VR=
- visual reproduction
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
CME Course: NPub.org/cmelist
- Received August 7, 2019.
- Accepted in final form February 19, 2020.
- © 2020 American Academy of Neurology
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