A 32-Month Follow-Up Study of the Effect of APOE ε4 on the Whole Brain Connection in Young Healthy Individuals.

• The time-by-APOE ε4 interaction on brain FC demonstrates at a young age. • After follow-up for nearly 3 years, young ε4 carriers reveal decreased FC among time. • And the left superior temporal gyrus is the most sensitive brain region. APOE ε4 is risk for cognitive decline even in normal aging, but its effect on the whole-brain functional connectivity (FC) among time in young adults remain elusive. This study aimed to validate the time-by- APOE ε4 interaction on brain FC of this specific population. Longitudinal changes in neuropsychological assessments and resting-state functional magnetic resonance imaging in 26 ε4 carriers and 26 matched non- ε4 carriers were measured for about 3 years. Whole-brain FC was calculated, and a full factorial design was used to compare the difference among groups. Two-sample t test was used for post-hoc analysis. Pearson's correlation analysis was conducted to investigate the relationships between FC and cognitive tests. Of 26 specially appointed ROIs, left superior temporal gyrus (TG) was most sensitive to the effect of time-by-gene interaction. Specifically, the alteration of FC was distributed between the left TG and right TG with GRF correction (voxel- P < 0.001, cluster- P < 0.05), and decreased in ε4 carriers while increased in non- ε4. The main effect of gene showed ε4 carriers has lower FC between left TG and right middle frontal gyrus as compared with non- ε4 both at baseline and follow-up study; ε4 carriers has lower FC between left TG and right supramarginal as compared with non- ε4 at baseline, but no difference in follow-up study. The time-by- APOE ε4 interaction on brain FC was demonstrated at a young age, and left TG was the earliest affected brain regions. The young adult ε4 carriers experience decreased FC among time in the absence overt clinical symptoms. [ABSTRACT FROM AUTHOR]