APOE ε4 Allele Modulates The Differential Effects of Education on Cognition in Alzheimer’s Continuum: The SILCODE Study

Abstract Background: Elders with subjective cognitive decline (SCD) in the absence of objective cognitive impairment are at increased risk of developing mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Previous study has reported that higher education was associated with better performance in cognitive performance in elderly people with SCD. However, it is not clear whether there is a differential effect of education on cognition between healthy controls (HC), individuals with SCD and patients with cognitive impairment (CI).Methods: We performed a cross-sectional study that included 186 HC, 279 SCD subjects and 79 patients with CI from the Sino Longitudinal Study on Cognitive Decline (SILCODE) project. A series of neuropsychological tests of memory, executive, language, and general cognitive function were used to assess the subjects cognitive performance. We performed multiple linear regression models to examine the effect of education on neuropsychological test scores in the total sample and then described differences in the effect according to three different groups. In addition, we presented the effect of education on total test score expressed as a global composite z-scores in the total sample and three different groups, respectively. Furthermore, we examined whether apolipoprotein E ε4 allele (APOE ε4) status would regulate the effect of education on the global composite score among three different groups.Results: Education has a positive effect on cognition in the total sample. Stratification for different groups showed that the positive effect of education on cognition is found in HC and SCD group, while education has a negative effect on cognition in the CI group. Furthermore, we found the APOE ε4 allele does not modify the positive effect of education on cognition in the HC group, but the APOE ε4 allele weaken that beneficial effect in the SCD group and maintain the negative effect in the CI group.Conclusions: High education may delay the progression from SCD to cognitive impairment and yield differential effects on cognition across the spectrum of AD. Furthermore, that differential effects are subjected to modulation by the APOE ε4 status.