APOE ε4 and cognitive reserve effects on the functional network in the Alzheimer’s disease spectrum

The apolipoprotein E (APOE) ε4 allele is a genetic risk factor for Alzheimer’s disease, whereas educational attainments have protective effects against cognitive decline in aging and patients with Alzheimer’s disease. We examined the possible effects of years of education and APOE genotype on the topological properties of the functional network in normal aging, mild cognitive impairment and Alzheimer’s disease. The years of education showed a significant, negative association with the local efficiency, clustering coefficient and small-worldness of functional networks in APOE ε4 noncarriers but not in ε4 carriers. These associations were mainly observed in normal aging and were reduced in mild cognitive impairment and Alzheimer’s disease. Moreover, regions of the inferior frontal gyrus, temporal pole, and cuneus also showed correlations between education and nodal degree. Our findings demonstrated that the protective effects of education persist in APOE ε4 noncarriers but diminish in ε4 carriers. In addition, the protective effects of education were attenuated or reduced in the progression of Alzheimer’s disease.