APOE ε4 Carrier Status and Cognitive Decline in Mild-to-Moderate Alzheimer’s Disease: A Linear Mixed-Effects Analysis of the Placebo Arm of EXPEDITION 1
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Background
Studies indicate that the apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD), and individuals with this allele are at increased risk of developing AD, there remains debate regarding whether APOE ε4 carriers experience more rapid cognitive decline over time compared to non-carriers. This study assessed this question using linear mixed-effects models applied to the placebo arm of EXPEDITION 1, a phase 3 clinical trial evaluating solanezumab in patients with mild-to-moderate Alzheimer’s disease.
Methods
In this study we utilized data from 370 participants in the placebo group of the EXPEDITION 1 trial. After excluding 27 participants with undefined APOE genotype, all models and analyses were applied to the remaining 343 participants (686 ADAS-Cog14 observations) to determine whether APOE ε4 carriers exhibit a faster rate of decline over the 80-week follow-up period. Five nested linear mixed-effects models with a participant-specific random intercept were fitted, and also a complementary change-score analysis was done.
Results
Over 80 weeks, ADAS-Cog14 worsened by an average of 7.01 points. Carriers did not decline faster than non-carriers (additional decline 1.31 points; 95% CI −1.22 to 3.83; p = 0.310), and the change-score analysis showed the same pattern. Carriers had worse ADAS-Cog14 scores overall, but this difference was no longer significant after adjustment for baseline CDR-SB.
Conclusion
In this cohort, APOE ε4 carrier status was related to disease severity at baseline rather than to the rate of cognitive decline over 80 weeks.
