Abstract
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.
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Acknowledgments
Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Funding
This project was supported by the National Key Research and Development Project (2018AAA0102601), the National Natural Science Foundation of China (61,503,272, 81,471,752, 81,771,824, 81,671,776, 61,727,807, 61,633,018, and 81,601,454), a project funded by the China Postdoctoral Science Foundation (2016 M601287), and the Scientific Research Foundation for Returned Overseas Chinese Scholars, the State Education Ministry, the National Key R&D Program of China (2018YFC0115400), the Beijing Municipal Science & Technology Commission (Z181100003118007, Z191100010618004) and the Beijing Nova Program (Z171100001117057).
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Li, T., Wang, B., Gao, Y. et al. APOE ε4 and cognitive reserve effects on the functional network in the Alzheimer’s disease spectrum. Brain Imaging and Behavior 15, 758–771 (2021). https://doi.org/10.1007/s11682-020-00283-w
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DOI: https://doi.org/10.1007/s11682-020-00283-w