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

The apolipoprotein E (APOE) epsilon 4 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 epsilon 4 noncarriers but not in epsilon 4 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 epsilon 4 noncarriers but diminish in epsilon 4 carriers. In addition, the protective effects of education were attenuated or reduced in the progression of Alzheimer's disease.

Automated summary

The years of education have significant effects on the topological properties of the functional network, especially in individuals without the APOE ε4 allele. These effects diminish in individuals with the ε4 allele and decrease as Alzheimer's disease progresses.