Associations between differential connectivity patterns of executive control networks and APOE ɛ4 in the Alzheimer continuum.

The APOE ɛ4 allele and age are risk factors for Alzheimer's disease (AD) and contribute to decreased executive function. However, the influence of APOE ɛ4 on the executive control network (ECN) in the AD continuum is still unclear. This study included 269 participants aged between 50 and 95 years old, based on ADNI data, including 104 cognitively normal (CN) individuals, 72 individuals with early mild cognitive impairment (EMCI), 55 individuals with late mild cognitive impairment (LMCI), and 38 AD patients. Within each disease group, participants were subdivided into APOE ɛ4 carriers and non-carriers. We explored brain regions within the ECN affected by the interactions between genes and disease states by resting-state functional magnetic resonance imaging (fMRI) and voxel-based two-way analysis of variance (ANOVA). Subsequently, functional connectivity (FC) between seeds and peak clusters were extracted and correlated with the cognitive performance. We found that the damages of carrying APOE ɛ4 in ECNs mainly distributed in the fronto-parietal and parietal-temporal systems. Functional network intergroup differences indicated increased intrafrontal and fronto-parietal connectivity at the early stage of AD and increased connectivity between the parietal lobe and related regions at late disease in these APOE ɛ4 carriers. Our conclusion is that the functional connectivity in the ECN exhibits different distinguishably patterns of impairment in the AD continuum under the influence of the APOE ɛ4 allele. Patients with different genotypes showed heterogeneity in functional network changes in the early stages of disease, which may be a potential biomarker for early AD.