Different posterior hippocampus and default mode network modulation in young APOE ε4 carriers: a functional connectome-informed phenotype longitudinal study.

To determine the functional connectome change pattern based on subregions of the hippocampus in young APOEε4 carriers during a 3-year follow-up. All the participants (n = 213) were tested for resting-state functional MRI, neuropsychological scales, and APOE genotype. The age- and sex-matched APOE ε4/ε3 (23.9 ± 3.2 years old, 6 female/7 male) carriers and APOE ε3/ε3 (22.9 ± 1.6 years old, 7 female/12 male) carriers were finally followed up. The hippocampus and its anterior/middle/posterior subregion-based functional connectivity (FC) patterns were compared between APOEε4 and APOEε3 groups by a two-sample t-test at baseline and mixed-effect analysis at follow-up. The effective connectivity (EC) patterns among the altered regions of interaction effect were examined in the APOEε4 groups. APOEε4 carries displayed saliently enhanced FC in the right anterior/middle hippocampus and core regions of the default mode network (DMN) (P < 0.05 by Gaussian Random Fields (GRF) correction). However, the APOEε4-by-time interaction was evident in the middle/posterior hippocampus with connection to the lateral temporal lobe and anterior cingulate cortex (ACC) (P < 0.05 by GRF correction). Moreover, the APOEε4 group at follow-up showed increased EC separately from both the left middle hippocampus and lateral temporal lobe to the left posterior hippocampus, and its changes of FC/EC significantly correlated with altered memory function. The posterior hippocampus might be especially vulnerable to early modulation in young APOEε4 carriers. Its connection with the lateral temporal lobe, rather than with DMN, might be the early compensative mechanism of memory function regulation influenced by APOE ε4 in the young adults.